Microbe-associated molecular pattern-induced calcium signaling requires the receptor-like cytoplasmic kinases, PBL1 and BIK1.
Plant perception of conserved microbe-derived or damage-derived molecules (so-called microbe- or damage-associated molecular patterns, MAMPs or DAMPs, respectively) triggers cellular signaling cascades to initiate counteracting defence responses. Using MAMP-induced rise in cellular calcium levels as one of the earliest biochemical readouts, we initiated a genetic screen for components involved in early MAMP signaling in Arabidopsis thaliana. We characterized here the "changed calcium elevation 5" (cce5) mutant, where five allelic cce5 mutants were isolated. They all show reduced calcium levels after elicitation with peptides representing bacteria-derived MAMPs (flg22 and elf18) and endogenous DAMP (AtPep1), but a normal response to chitin octamers. Mapping, sequencing of the mutated locus and complementation studies revealed CCE5 to encode the receptor-like cytoplasmic kinase (RLCK), avrPphB sensitive 1-like 1 (PBL1). Kinase activities of PBL1 derived from three of the cce5 alleles are abrogated in vivo. Validation with T-DNA mutants revealed that, besides PBL1, another RLCK, Botrytis-induced kinase 1 (BIK1), is also required for MAMP/DAMP-induced calcium elevations. Hence, PBL1 and BIK1 (but not two related RLCKs, PBS1 and PBL2) are required for MAMP/DAMP-induced calcium signaling. It remains to be investigated if the many other RLCKs encoded in the Arabidopsis genome affect early calcium signal transduction - perhaps in dependence on the type of MAMP/DAMP ligands. A future challenge would be to identify the substrates of these various RLCKs, in order to elucidate their signaling role between the receptor complexes at the plasma membrane and downstream cellular signaling components.


Magnetic Resonance Imaging Parameters at 1 Year Correlate With Clinical Outcomes Up to 17 Years After Autologous Chondrocyte Implantation.
The ability to predict the long-term success of surgical treatment in orthopaedics is invaluable, particularly in clinical trials. The quality of repair tissue formed 1 year after autologous chondrocyte implantation (ACI) in the knee was analyzed and compared with clinical outcomes over time. Better quality repair tissue and a better appearance on magnetic resonance imaging (MRI) 1 year after ACI lead to improved longer-term clinical outcomes. Cohort study; Level of evidence, 3. Repair tissue quality was assessed using either MRI (11.5 ± 1.4 [n = 91] or 39.2 ± 18.5 [n = 76] months after ACI) or histology (16.3 ± 11.0 months [n = 102] after ACI). MRI scans were scored using the whole-organ magnetic resonance imaging score (WORMS) and the magnetic resonance observation of cartilage repair tissue (MOCART) score, with additional assessments of subchondral bone marrow and cysts. Histology of repair tissue was performed using the Oswestry cartilage score (OsScore) and the International Cartilage Repair Society (ICRS) II score. Clinical outcomes were assessed using the modified Lysholm score preoperatively, at the time of MRI or biopsy, and at a mean 8.4 ± 3.7 years (maximum, 17.8 years) after ACI. At 12 months, the total MOCART score and some of its individual parameters correlated significantly with clinical outcomes. The degree of defect fill, overall signal intensity, and surface of repair tissue at 12 months also significantly correlated with longer-term outcomes. The presence of cysts or effusion (WORMS) significantly correlated with clinical outcomes at 12 months, while the presence of synovial cysts/bursae preoperatively or the absence of loose bodies at 12 months correlated significantly with long-term clinical outcomes. Thirty percent of repair tissue biopsies contained hyaline cartilage, 65% contained fibrocartilage, and 5% contained fibrous tissue. Despite no correlation between the histological scores and clinical outcomes at the time of biopsy, a lack of hyaline cartilage or poor basal integration was associated with increased pain; adhesions visible on MRI also correlated with significantly better histological scores. These results demonstrate that MRI at 12 months can predict longer-term clinical outcomes after ACI. Further investigation regarding the presence of cysts, effusion, and adhesions and their relationship with histological and clinical outcomes may yield new insights into the mechanisms of cartilage repair and potential sources of pain.


Linearization-based method for solving a multicomponent diffusion phase-field model with arbitrary solution thermodynamics.
This article describes a phase-field model for an isothermal multicomponent, multiphase system which avoids implicit interfacial energy contributions by starting from a grand potential formulation. A method is developed for incorporating arbitrary forms of the equilibrium thermodynamic potentials in all phases to determine an explicit relationship between chemical potentials and species concentrations. The model incorporates variable densities between adjacent phases, defect migration, and dependence of internal pressure on object dimensions ranging from the macro- to nanoscale. A demonstrative simulation of an overpressurized nanoscopic intragranular bubble in nuclear fuel migrating to a grain boundary under kinetically limited vacancy diffusion is shown.


Diagnostic performance of total-body 18F-FDG PET/CT with fast 2-min acquisition for liver tumours: comparison with conventional PET/CT.
To comparatively evaluate the diagnostic performances of total-body 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) with fast 2-min acquisition and conventional PET/CT in liver cancer patients. This study included 156 patients with liver tumours. Seventy-eight patients underwent total-body PET/CT. PET raw data were reconstructed using acquisition durations of 2 min (G2) and 15 min (G15). Another 78 patients with liver lesions (control patients) underwent conventional uMI780 PET/CT (G780). All patients were evaluated based on TNM staging. The maximum tumour standardized uptake value (tumour SUVmax), mean normal liver SUV (SUVmean), and tumour SUVmax-to-liver SUVmean ratio (TLR) were determined for all patients. G15 data were used as the reference in the lesion detectability analysis. The diagnostic performances of PET/CT in terms of visual parameters and of PET in terms of semi-quantitative parameters such as SUVmax and TLR were evaluated. Receiver operating characteristics (ROC) curve analysis of SUVmax and TLR at G2 was performed. Pathologic findings of surgical specimens served as the gold standard for all patients. The lesions found in G15 were also noted in G2; three lymph nodes were missed in G2. However, no significant difference was found in the TNM stage among G2, G15, and G780. For benign and malignant lesions, the liver SUVmean in G2 and G15 was higher than that in G780 (all P < 0.05). The tumour SUVmax and TLR in G2 were equivalent to those in G15 and G780 regardless of whether the lesions were benign or malignant. ROC curve analysis (SUVmax cutoff: 4.34, TLR cutoff: 1.34) demonstrated that G2 also had good sensitivity in detecting liver cancer. The diagnostic performance of total-body PET/CT in G2 was comparable to that in G15 among liver cancer patients. Further, the diagnostic efficiency of total-body PET/CT imaging with fast 2-min acquisition and conventional PET/CT was similar.


[The change and the clinical significance of peripheral blood Th1/Th2 cells in patients with pulmonary tuberculosis].
To study the change of peripheral blood CD4+ helper T cells and T helper subtype I and II (Th1/Th2) in patients with pulmonary tuberculosis and to explore their changes during anti-tuberculosis chemotherapy. CD4+ T cells from 105 patients with pulmonary tuberculosis and 25 normal controls were counted by Flow Cytometry. Peripheral blood cells were stimulated in vitro by phorbol myristate acetate (PMA) (25 ng/ml) and ionomycin (250 ng/ml). Cytokines were confined to the cells by using the protein transporting inhibitor containing monensin (2 micro mol/ml). These cells were incubated in 5% CO(2) for 4 h-4.5 h. The membrane and plasma of CD4+ helper T cells were marked by CD3 -PC5 + CD8 -FITC + INF-gamma -PE/CD3 -PC5 + CD8 -FITC + IgG1 -PE, CD3 -PC5 + CD8 -FITC + IL-4 -PE/CD3 -PC5 + CD8 -FITC + IgG1 -PE monoclonal antibodies respectively. Th1 and Th2 cells were counted and the ratio of Th1/Th2 cells was calculated. The levels of Th1 and Th2 cells in the 67 patients with pulmonary tuberculosis were detected at the end of intensive chemotherapy and at the sixth month of chemotherapy. (1) The levels of CD4+ T and Th1 cells in patients with tuberculosis were significantly lower than those of controls. Their values were (663 +/- 160)/ microl vs (735 +/- 156)/ microl and (9.56 +/- 3.60)% vs (18.7 +/- 5.03)% respectively (P < 0.05). (2) The levels of CD4+ T and Th1 cells in patients with severe pulmonary tuberculosis were lower than those in patients with moderate or mild pulmonary tuberculosis. Their values were (579 +/- 120)/ microl vs (726 +/- 166)/ microl, (684 +/- 192)/ microl and (5.43 +/- 2.33)% vs (12.2 +/- 1.81)% and (10.9 +/- 2.30)% respectively (P < 0.05). The level of Th2 cells was in contrast to Th1 cells and their values were (5.63 +/- 1.26)% vs (2.93 +/- 0.87)% and (3.22 +/- 1.01)% (P < 0.01). (3) The level of Th1 cells increased while that of Th2 decreased in the 61 patients who gradually recovered. (4) The level of Th2 cells in patients with smear positive tuberculosis was strikingly higher than that in patients with smear negative tuberculosis and their values were (5.20 +/- 0.97)% vs (2.77 +/- 1.96)% (P < 0.05). The detection of CD4+ helper T cells and Th1/Th2 cells in the peripheral blood cells from patients with pulmonary tuberculosis is useful in evaluating the state of disease and the effect of chemotherapy.


Non-antibiotic prevention of urinary tract infection.
The identification of several glycoconjugates as receptors for attaching bacteria has resulted in optimism regarding the use of receptor analogues in preventing infection. The structure of receptor-active oligosaccharides and the patient groups which might benefit from such treatment are most thoroughly understood for urinary tract infections. Prevention of adhesion and delay or decrease of infection was achieved using oligosaccharides from the globoseries of glycolipids containing Gal alpha 1----4Gal. This minimal receptor structure as a free saccharide was, however, not sufficient. It was the intact P, P1 and pk determinants which showed optimal activity in vitro. In addition, protection against experimental UTI results from previous exposure to whole bacteria or isolated antigens. The mechanism(s) of protection and their relevance in clinical UTI remain to be defined.


Early detection of subclinical organ dysfunction by microdialysis of the rectus abdominis muscle in a porcine model of critical intra-abdominal hypertension.
The aim of this study was to evaluate microdialysis of the rectus abdominis muscle (RAM) for early detection of subclinical organ dysfunction in a porcine model of critical intra-abdominal hypertension (IAH). Microdialysis catheters for analyses of lactate, pyruvate, and glycerol levels were placed in cervical muscles (control), gastric and jejunal wall, liver, kidney, and RAM of 30 anesthetized mechanically ventilated pigs. Catheters for venous lactate and interleukin 6 samples were placed in the jugular, portal, and femoral vein. Intra-abdominal pressure (IAP) was increased to 20 mmHg (IAH20 group, n = 10) and 30 mmHg (IAH30, n = 10) for 6 h by controlled CO2 insufflation, whereas sham animals (n = 10) exhibited a physiological IAP. In contrast to 20 mmHg, an IAH of 30 mmHg induced pathophysiological alterations consistent with an abdominal compartment syndrome. Microdialysis showed significant increase in the lactate/pyruvate ratio in the RAM of the IAH20 group after 6 h. In the IAH30 group, the strongest increase in lactate/pyruvate ratio was detected in the RAM and less pronounced in the liver and gastric wall. Glycerol increased in the RAM only. After 6 h, there was a significant increase in venous interleukin 6 of the IAH30 group compared with baseline. Venous lactate was increased compared with baseline and shams in the femoral vein of the IAH30 group only. Intra-abdominal pressure-induced ischemic metabolic changes are detected more rapidly and pronounced by microdialysis of the RAM when compared with intra-abdominal organs. Thus, the RAM represents an important and easily accessible site for the early detection of subclinical organ dysfunction during critical IAH.


Molecular imaging of pulmonary diseases.
Imaging holds an important role in the diagnosis of lung diseases. Along with clinical tests, noninvasive imaging techniques provide complementary and valuable information that enables a complete differential diagnosis. Various novel molecular imaging tools are currently under investigation aimed toward achieving a better understanding of lung disease physiopathology as well as early detection and accurate diagnosis leading to targeted treatment. Recent research on molecular imaging methods that may permit differentiation of the cellular and molecular components of pulmonary disease and monitoring of immune activation are detailed in this review. The application of molecular imaging to lung disease is currently in its early stage, especially compared to other organs or tissues, but future studies will undoubtedly reveal useful pulmonary imaging probes and imaging modalities.


Loss of ctnnd2b affects neuronal differentiation and behavior in zebrafish.
Delta-catenin (CTNND2) is an adhesive junction associated protein belonging to the family of p120 catenins. The human gene is located on the short arm of chromosome 5, the region deleted in Cri-du-chat syndrome (OMIM #123450). Heterozygous loss of CTNND2 has been linked to a wide spectrum of neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Here we studied how heterozygous loss of ctnnd2b affects zebrafish embryonic development, and larvae and adult behavior. First, we observed a disorganization of neuronal subtypes in the developing forebrain, namely the presence of ectopic isl1-expressing cells and a local reduction of GABA-positive neurons in the optic recess region. Next, using time-lapse analysis, we found that the disorganized distribution of is1l-expressing forebrain neurons resulted from an increased specification of Isl1:GFP neurons. Finally, we studied the swimming patterns of both larval and adult heterozygous zebrafish and observed an increased activity compared to wildtype animals. Overall, this data suggests a role for ctnnd2b in the differentiation cascade of neuronal subtypes in specific regions of the vertebrate brain, with repercussions in the animal's behavior.


hiPSC Disease Modeling of Rare Hereditary Cerebellar Ataxias: Opportunities and Future Challenges.
Cerebellar ataxias are clinically and genetically heterogeneous diseases affecting primary cerebellar cells. The lack of availability of affected tissue from cerebellar ataxias patients is the main obstacle in investigating the pathogenicity of these diseases. The landmark discovery of human-induced pluripotent stem cells (hiPSC) has permitted the derivation of patient-specific cells with an unlimited self-renewing capacity. Additionally, their potential to differentiate into virtually any cell type of the human organism allows for large amounts of affected cells to be generated in culture, converting this hiPSC technology into a revolutionary tool in the study of the mechanisms of disease, drug discovery, and gene correction. In this review, we will summarize the current studies in which hiPSC were utilized to study cerebellar ataxias. Describing the currently available 2D and 3D hiPSC-based cellular models, and due to the fact that extracerebellar cells were used to model these diseases, we will discuss whether or not they represent a faithful cellular model and whether they have contributed to a better understanding of disease mechanisms.


[Comparison of albumin analysis by fluorescent method with other clinical laboratory parameters in purulent peritonitis].
The concentration and properties of the blood-albumin linkage centers were examined by the method fluorescent probes, besides, the general clinical-and-laboratory indices in the blood serum of patients with diffusive purulent peritonitis were determined. The parameters as obtained by the method of fluorescent probes revealed a valuable information on a patients' severity condition and on a forecasted disease evolution; finally, they surpass, in a majority of cases, the generally accepted clinical-and-laboratory tests applicable to similar conditions.


Breaking the left-right axis: do nodal parcels pass a signal to the left?
In mammals, left-right symmetry is broken by a mechanically driven leftward flow of liquid at the embryonic node (nodal flow). Various models have emerged explaining how this may happen. Work from Tanaka and colleagues has provided a new mechanism by which nodal flow may be breaking symmetry. They describe small membrane-bound particles, which they term nodal vesicular parcels (NVPs), that are carried to the left side of the node. In the paper, they argue how signals carried within these parcels may break L-R symmetry.


Targeted therapy for gynecologic cancers: Toward the era of precision medicine.
Recent advances in molecular biology of cancer have led to the development of targeted agents, mainly of monoclonal antibodies and small-molecule compounds. Unlike traditional drugs that inhibit DNA synthesis and mitosis, these agents target the signaling pathways of cancer cells, stroma, and vasculature in tumor tissues. For gynecologic cancers, drugs targeting angiogenesis such as anti-VEGF antibody have been used in the treatment of advanced or recurrent ovarian and cervical cancers, and the drugs targeting homologous recombination deficiency such as PARP inhibitors have been approved for maintenance after chemotherapy in platinum-sensitive ovarian cancer. In addition, novel immunotherapy using the immune checkpoint inhibitors such as anti-PD-1 antibody has received much attention for modulation of local immunity, resulting in the durable response of platinum-resistant ovarian cancer. In the precision medicine era, further understanding of cancer genomics and identification of predictive biomarkers are essential to ensure better health for women with gynecologic cancer.


Metalation of 4-oxazolinyloxazole derivatives. A convenient route to 2,4-bifunctionalized oxazoles.
The synthesis of an array of 5-phenyloxazole derivatives bearing a variety of hydroxyalkyl groups at the C-2 position of the heterocyclic nucleus and possessing a formyl or a carboxyl function at C-4 is reported. These bifunctionalized compounds have been efficiently prepared by addition of carbonylated electrophiles to the 2-lithio derivative of 5-phenyloxazole preliminarily equipped with an oxazoline unit at the 4-position of the oxazole nucleus. It is demonstrated that this protocol offers a double advantage since it suppresses the troublesome electrocyclic ring-opening reaction and allows access to the target compounds by simple chemical transformation of the oxazoline ring system.


Diagnosis, differential diagnosis and nosologic classification of the dementia syndrome.
Some clinical aspects of the diagnosis, differential diagnosis, and the nosologic classification of the dementia syndrome are presented. In discussing the definition of the dementia syndrome and its differentation from other organic brain syndromes, the criteria of DSM III are taken into account. Considering the nosological classification of the dementia syndrome particular emphasis is placed on the most frequent diseases in the senium, the Multi-Infarct Dementias (MID) and the primary degenerative dementias (PDD, according to DSM III). The clinical problems in differentiating MID from PDD and Morbus Pick from the dementia of the Alzheimer type in the group of are discussed in more detail.


Intrinsic contact angle of aqueous phases at membranes and vesicles.
Biomimetic membranes exposed to several aqueous phases are studied theoretically. Specific examples are provided by lipid vesicles and phase separating polymer solutions. The theory reveals the existence of an intrinsic contact angle, theta(in), between the membranes and the aqueous phases. An explicit relation is derived by which this intrinsic angle can be determined from the effective contact angles as measured by optical microscopy. A detailed comparison between theory and experiment provides strong evidence that the intrinsic contact angle theta(in) represents a material parameter, in contrast to the effective contact angles.


Bioprospecting Microbial Diversity for Lignin Valorization: Dry and Wet Screening Methods.
Lignin is an abundant cell wall component, and it has been used mainly for generating steam and electricity. Nevertheless, lignin valorization, i.e. the conversion of lignin into high value-added fuels, chemicals, or materials, is crucial for the full implementation of cost-effective lignocellulosic biorefineries. From this perspective, rapid screening methods are crucial for time- and resource-efficient development of novel microbial strains and enzymes with applications in the lignin biorefinery. The present review gives an overview of recent developments and applications of a vast arsenal of activity and sequence-based methodologies for uncovering novel microbial strains with ligninolytic potential, novel enzymes for lignin depolymerization and for unraveling the main metabolic routes during growth on lignin. Finally, perspectives on the use of each of the presented methods and their respective advantages and disadvantages are discussed.


Use of whole genome amplification to rescue DNA from plasma samples.
While DNA of good quality and sufficient amount can be obtained easily from whole blood, buccal swabs, surgical specimens, or cell lines, these DNA-rich sources are not always available. This is particularly the case in studies for which biological specimens were collected when genotyping assays were not widely available. In those studies, serum or plasma is often the only source of DNA. Newly developed whole genome amplification (WGA) methods, based on phi29 polymerase, may play a significant role in recovering DNA in such instances. We tested a total of 528 plasma samples kept in storage at -40 degrees C for approximately 10 years for 8 single nucleotide polymorphisms (SNPs) using the 5' exonuclease (TaqMan) assay. These specimens yielded undetectable levels of DNA following extraction with an affinity column but produced an average 52.7 microg (standard deviation of 31.2 microg) of DNA when column-extracted DNA was used as a template for WGA. This increased the genotyping success rate from 54% to 93%. There were only 3 disagreements out of 364 paired genotyping results for pre- and post-WGA DNAs, indicating an error rate of 0.82%. These results are encouraging for expanding the use of poor DNA resources in genotyping studies.


Percentage of weight loss as a predictor of surgical risk: from the time of Hiram Studley to today.
Hiram Studley's 1936 article of research was the first publication to present a connection between preoperative weight loss and adverse postoperative outcome. Almost 70 years later, weight loss remains one of the most prominently used tools to assess nutritional status and predict surgical risk. This paper provides an overview of surgical practices at the time of Dr Studley and demonstrates Studley's unique contributions to the field of nutrition support. The search for more accurate methods of preoperative nutrition assessment is traced to show how subsequent research continues to validate the use of weight loss in the assessment of surgical risk. New developments center on techniques of body composition assessment to quantify weight lost as functional weight and clarify the impact of malnutrition on operative outcome.


Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center.
Myelodysplastic syndrome (MDS), a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce. (1) To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2) to study its progression to acute myeloid leukemia (AML) in the selected patients over the study period. A prospective observational study was performed with patients from Department of Medicine and Hematology, Government Medical College, Kozhikode, who were diagnosed with MDS within the study period (from 1 January 2014 to 31 July 2015). Secondary causes of dysplasia were excluded. In possible cases, the international prognostic scoring system was followed. These patients were followed up for an additional 6 months to assess the progression of MDS to AML based on symptoms, signs, hemogram, or repeat peripheral smear/bone marrow studies. Of the 60 patients, 73% were aged >60 years. Disease was common in males, with a male:female ratio of 7:3. Thirty-five percent of the patients were working in agricultural and allied fields and had pesticide exposure. Patients with prior radiation exposure had significant association with adverse outcome. Fatigue was the prominent symptom and was reported by 90% of the patients. Blasts were >5% in peripheral smear; bone marrow cytopenia and dysplasia at the time of diagnosis had significant association with risk of transforming to AML. Refractory anemia (RA), observed in 22 patients, was the most common type of MDS. Most of the patients with RA with excess blasts type-1 and RA with excess blasts type-2 transformed to AML, and the association was statistically significant. Deletion of short arm of fifth chromosome (5q deletion) was detected in 11 patients. All of them showed good response to treatment with lenalidomide and had a favorable outcome. This study highlights the various etiological factors, and the clinical profile of MDS seen in the Indian population. Cytogenetic analysis and application of the international prognostic scoring system has a significant bearing on the outcome, as exemplified by the response to lenalidomide in patients with 5q deletion. This study also indicates that proper diagnostic and prognostic assessment is necessary to institute appropriate therapeutic options.


Professional development programs in health promotion: tools and processes to favor new practices.
Developing innovative interventions that are in sync with a health promotion paradigm often represents a challenge for professionals working in local public health organizations. Thus, it is critical to have both professional development programs that favor new practices and tools to examine these practices. In this case study, we analyze the health promotion approach used in a pilot intervention addressing children's vulnerability that was developed and carried out by participants enrolled in a public health professional development program. More specifically, we use a modified version of Guichard and Ridde's (Une grille d'analyse des actions pour lutter contre les inégalités sociales de santé. In Potvin, L., Moquet, M.-J. and Jones, C. M. (eds), Réduire les Inégalités Sociales en Santé. INPES, Saint-Denis Cedex, pp. 297-312, 2010) analytical grid to assess deductively the program participants' use of health promotion practices in the analysis and planning, implementation, evaluation, sustainability and empowerment phases of the pilot intervention. We also seek evidence of practices involving (empowerment, participation, equity, holism, an ecological approach, intersectorality and sustainability) in the intervention. The results are mixed: our findings reveal evidence of the application of several dimensions of health promotion (equity, holism, an ecological approach, intersectorality and sustainability), but also a lack of integration of two key dimensions; that is, empowerment and participation, during various phases of the pilot intervention. These results show that the professional development program is associated with the adoption of a pilot intervention integrating multiple but not all dimensions of health promotion. We make recommendations to facilitate a more complete integration. This research also shows that the Guichard and Ridde grid proves to be a thorough instrument to document the practices of participants.


New method of forced implantation of permanent catheters for hemodialysis into critically stenosed or occluded central veins.
The aim of the study was to report a novel technique of forced implantation of catheters for hemodialysis into critically stenosed or occluded central veins, without preceding angioplasty or stenting. Sixteen patients with central venous occlusive disease, requiring urgent hemodialysis underwent this procedure. Catheterization of stenosis - occlusion was initially performed with soft guidewire, subsequently exchanged to stiff guidewire. Forced insertion of dilators, peel-off sheath throughout the stenosis or occlusion and finally implantation of the catheter completed the procedure. Our technique does not require pre-procedural angioplasty or stent deployment. In all patients postoperative hemodialysis was managed with satisfactory adequacy. No early or late complications related to the procedure occurred. We did not observe any clinically significant aggravation of symptoms of central vein stenosis or occlusion. Complications, not-related to the procedure included one, late skin entry site infection and one, late catheter thrombosis. These were managed without the necessity of catheter exchange. Our technique of forced implantation of catheters for hemodialysis into critically stenosed or occluded central veins without previous balloon predilatation or stenting is simple and diminishes the total cost of the procedure. Provides quick vascular access for hemodialysis in life threatening situations.


Plasmid-mediated resistance to gentamicin in Staphylococcus aureus: the involvement of a transposon.
Resistance to gentamicin, tobramycin and kanamycin (GmrTmrKmr) in strains of Staphylococcus aureus isolated from clinical sources in Australia is mediated by a 4.7 kb transposable element, designated Tn4001. A 2.5 kb HindIII fragment which maps symmetrically within Tn4001, and encompasses the aminoglycoside-resistance coding region, has been shown to hybridise with fragments of identical size in HindIII digests of three different GmrTmrKmr plasmids, two of which were self-transmissible, from strains of S. aureus isolated in the USA. Examination by electronmicroscopy of self-annealed molecules of the North American GmrTmrKmr plasmids revealed the presence of stem and loop structures similar to those produced by Tn4001, but with shorter inverted repeats. These results suggest that GmrTmrKmr in strains of S. aureus isolated in the USA is, or once was, transposable, and that transposable elements analogous to Tn4001 may be found in isolates of GmrTmrKmr S. aureus worldwide.


A Review on Controlling Grain Boundary Character Distribution during Twinning-Related Grain Boundary Engineering of Face-Centered Cubic Materials.
Grain boundary engineering (GBE) is considered to be an attractive approach to microstructure control, which significantly enhances the grain-boundary-related properties of face-centered cubic (FCC) metals. During the twinning-related GBE, the microstructures are characterized as abundant special twin boundaries that sufficiently disrupt the connectivity of the random boundary network. However, controlling the grain boundary character distribution (GBCD) is an extremely difficult issue, as it strongly depends on diverse processing parameters. This article provides a comprehensive review of controlling GBCD during the twinning-related GBE of FCC materials. To commence, this review elaborates on the theory of twinning-related GBE, the microscopic mechanisms used in the optimization of GBCD, and the optimization objectives of GBCD. Aiming to achieve control over the GBCD, the influence of the initial microstructure, thermo-mechanical processing (TMP) routes, and thermal deformation parameters on the twinning-related microstructures and associated evolution mechanisms are discussed thoroughly. Especially, the development of twinning-related kinetics models for predicting the evolution of twin density is highlighted. Furthermore, this review addresses the applications of twinning-related GBE in enhancing the mechanical properties and corrosion resistance of FCC materials. Finally, future prospects in terms of controlling the GBCD during twinning-related GBE are proposed. This study will contribute to optimizing the GBCD and designing GBE routes for better grain-boundary-related properties in terms of FCC materials.


[A model to measure the volume of choroidal melanomas (author's transl)].
A formula to calculate the volume of biconvex-shaped malignant melanomata of the choroid is presented. The axial length of the eye, whatever the refractive error, has nearly no influence on the results. A computer printout of the range of results is added for clinical use. The reliability of contact B-Scan ultrasonography to obtain those parameters is examined using various tumor models of defined sizes.


Use of ultrasonography in the detection of ureteric reflux in children suspected of having urinary infection.
The present study investigated whether ultrasonography was effective in detecting ureteric reflux in children suspected of having urinary infection. Seventeen children with febrile episodes and pyuria were enrolled. The ultrasound examination revealed ballooning of the renal pelvis during bladder contraction in 4 children, dilatation of the distal ureters in 6, and small kidney in 2. Cystography was performed on the 6 children with these ultrasound abnormalities and 1 child with two episodes of suspected urinary infection. Four children showed reflux. All of the 4 children had been found to have renal pelvic ballooning on ultrasound. None of the 10 children who did not undergo cystography had recurrence of urinary infection or significant bacteriuria during a median follow-up period of 12 months. Thus, scanning during bladder contraction was effective in detecting significant ureteric reflux.


Complete response of skull base inverted papilloma to chemotherapy: Case report.
Inverted papilloma (IP) is the most common benign sinonasal neoplasm. Endoscopic techniques, improved understanding of pathophysiology, and novel surgical approaches have allowed rhinologists to treat IPs more effectively, with surgery being the mainstay of therapy. Frontal sinus IP poses a challenge for surgical therapy due to complex anatomy and potentially difficult surgical access. We reported a unique case of a massive frontal sinus IP that presented with intracranial and orbital extension, with near resolution after chemotherapy. A retrospective case review of a patient with a frontal sinus IP treated at a tertiary academic medical center. A 75-year-old male patient presented with nasal obstruction, purulent nasal discharge, and a growing left supraorbital mass. Endoscopy demonstrated a mass that filled both frontal and ethmoid sinuses, with orbital invasion. There also was substantial erosion of the posterior table, which measured 1.73 × 1.40 cm. A biopsy specimen demonstrated IP with carcinoma in situ. The patient was deemed unresectable on initial evaluation and, subsequently, underwent chemotherapy (carboplatin and paclitaxel). The tumor had a dramatic response to chemotherapy, and the patient elected for definitive surgery to remove any residual disease. During surgery, only a small focus of IP was found along the superior wall of the frontal sinus. No tumor was found elsewhere, including at the site of skull base erosion. The final pathology was IP without carcinoma in situ or dysplasia. This was the first reported case of chemotherapeutic "debulking" of IP, which facilitated surgical resection, despite substantial intracranial and orbital involvement. Although nearly all IPs can be treated surgically, rare cases, such as unresectable tumors, may benefit from systemic chemotherapy.


Importance of the Colmation Layer in the Transport and Removal of Cyanobacteria, Viruses, and Dissolved Organic Carbon during Natural Lake-Bank Filtration.
This study focused on the importance of the colmation layer in the removal of cyanobacteria, viruses, and dissolved organic carbon (DOC) during natural bank filtration. Injection-and-recovery studies were performed at two shallow (0.5 m deep), sandy, near-shore sites at the southern end of Ashumet Pond, a waste-impacted, kettle pond on Cape Cod, MA, that is subject to periodic blooms of cyanobacteria and continuously recharges a sole-source drinking-water aquifer. The experiment involved assessing the transport behaviors of bromide (conservative tracer), sp. IU625 (cyanobacterium, 2.6 ± 0.2 µm), AS-1 (tailed cyanophage, 110 nm long), MS2 (coliphage, 26 nm diameter), and carboxylate-modified microspheres (1.7 µm diameter) introduced to the colmation layer using a bag-and-barrel (Lee-type) seepage meter. The injectate constituents were tracked as they were advected across the pond water-groundwater interface and through the underlying aquifer sediments under natural-gradient conditions past push-point samplers placed at ∼30-cm intervals along a 1.2-m-long, diagonally downward flow path. More than 99% of the microspheres, IU625, MS2, AS-1, and ∼44% of the pond DOC were removed in the colmation layer (upper 25 cm of poorly sorted bottom sediments) at two test locations characterized by dissimilar seepage rates (1.7 vs. 0.26 m d). Retention profiles in recovered core material indicated that >82% of the attached IU625 were in the top 3 cm of bottom sediments. The colmation layer was also responsible for rapid changes in the character of the DOC and was more effective (by three orders of magnitude) at removing microspheres than was the underlying 20-cm-thick segment of sediment.


Incidence, prevalence and mortality of anorexia nervosa and bulimia nervosa.
To review the recent literature on the epidemiology of anorexia nervosa and bulimia nervosa in terms of incidence, prevalence and mortality. Although the overall incidence rate of anorexia nervosa is considerably stable over the past decades, the incidence among younger persons (aged <15 years) has increased. It is unclear whether this reflects earlier detection or earlier age of onset. Nevertheless, it has implications for future research into risk factors and for prevention programs. For bulimia nervosa, there has been a decline in overall incidence rate over time. The lifetime prevalence rates of anorexia nervosa might be up to 4% among females and 0.3% among males. Regarding bulimia nervosa, up to 3% of females and more than 1% of males suffer from this disorder during their lifetime. While epidemiological studies in the past mainly focused on young females from Western countries, anorexia nervosa and bulimia nervosa are reported worldwide among males and females from all ages. Both eating disorders may carry a five or more times increased mortality risk. Anorexia nervosa and bulimia nervosa occur worldwide among females and males of all age groups and are associated with an increased mortality risk.


Spectrally encoded extended source optical coherence tomography.
We have developed an extended source optical coherence tomography (SEES-OCT) technique in an attempt to improve signal strength for ophthalmic imaging. A line illumination with a visual angle of 7.9 mrad is produced by introducing a dispersive element in the infinity space of the sample arm. The maximum permissible exposure (MPE) of such an extended source is 3.1 times larger than that of a "standard" point source OCT, which corresponds to sensitivity improvement of 5 dB. The advantage of SEES-OCT in providing superior penetration depth over a point source system is demonstrated using swine eye tissues ex vivo.


A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design.
Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences. We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly. This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.


The andrologist from medicine of reproduction to sexual medicine: the Italian experience.
The main andrological areas of interest, male reproductive and - more recently - sexual dysfunctions are most appropriately viewed as symptoms of the couple with medical, psychological and behavioural components that cannot be treated in a mechanical, purely medicinal manner (sexual medicine). The patient and his sexual partner must be active participants in a full continuum of care (medical sexology), the new challenge for the renewed and enriched field of andrology. In this field, the cooperation between basic researchers (such as geneticists, neurophysiologists, pharmacologists, ethologists) and a wide group of clinicians (such as endocrinologists, psychologists and psycho-sexologists, psychiatrists, urologists and gynaecologists) is of paramount importance for the andrologist at the dawn of the new field of medical sexology, which will be full of scientific gratification in the years to come.


Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules.
Copolymer 1 (Cop 1, poly (Y, E, A, K)) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS). Cop 1 binds promiscuously, with high affinity and in a peptide-specific manner to purified MS-associated HLA-DR2 (DRB1*1501) and rheumatoid arthritis-associated HLA-DR1 (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules. In the present work at least 95% of added Cop 1 could be bound to recombinant "empty" HLA-DR1 and -DR4, and 80% could be bound to HLA-DR2 proteins. Amino acid composition, HPLC profiles, and sequencing patterns of Cop 1 eluted by acid extraction from HLA-DR molecules were similar to those of the unseparated Cop 1. Protruding N-terminal ends of Cop 1 bound to HLA-DR1, -DR2, or -DR4 molecules were then treated with aminopeptidase I, followed by elution, HPLC, and pool sequencing. In contrast to untreated or unbound Cop 1, this material exhibited distinct motifs at some positions with increases in levels of E at the first and second cycles, of K at the second and third cycles, and of Y (presumably at P1 of the bound peptide) at the third to fifth cycles, regardless of the HLA-DR molecule employed. No preference was seen at the following cycles that were mainly A. These first pooled HLA-DR binding epitopes provide clues to the components of Cop 1 that are biologically active in suppressing MS and possibly rheumatoid arthritis.


Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines.
High-resolution two-dimensional gel electrophoresis (2-DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2-DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent (56/727) of the consistently detected proteins were found in significantly (P< 0.001) variable levels among the cell lines. Eight proteins present in normal cultured breast epithelial cells were not detected in any of the tumor cell lines. We identified a subset of the differentially expressed proteins using a combination of immunostaining, protein sequencing, comigration, and subcellular fractionation. These identified proteins include the intermediate filament components vimentin and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27 and hsp60 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Many of the differentially expressed proteins we identified have roles in cellular proliferation and differentiation, including annexin V, elongation initiation factor 5A, Rho GDP dissociation inhibitor, and prohibitin. We identified inosine-5-monophosphate dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells. These results expand the human breast epithelial cell protein database (http:// www.anl.gov/CMB/PMG) which is being built to assist researchers with the identification of abnormal patterns of expression and pathways associated with malignancy.


Interleukin-5, eosinophilic diseases and therapeutic intervention.
Interleukin 5 (IL-5) is the key cytokine in an eosinophil's life span: it supports eosinophilopoiesis and eosinophil differentiation, contributes to eosinophil migration, tissue localisation and function, and prevents eosinophil apoptosis. Given the likely role of eosinophils in chronic inflammatory diseases, a lot of research over the past decade was aimed at antagonising IL-5 function. It appears from recent studies that, although this can easily be achieved in vitro, blocking IL-5 function in vivo is much more difficult than originally anticipated. Here, we review the current status of IL-5 and IL-5 receptor research, with emphasis on strategies to interfere with IL-5 function.


Angiotensin converting enzyme in rat brain visualized by quantitative in vitro autoradiography.
Angiotensin converting enzyme was localized in rat brain by quantitative in vitro autoradiography using an [125I]labelled converting enzyme inhibitor called "351A". This radioligand was found to bind with high affinity and specificity to angiotensin converting enzyme. Very high levels of converting enzyme were observed in the ventricular choroid plexus, ependyma of all ventricles and large and medium blood vessels, subfornical organ, and organum vasculosum of the lamina terminalis. High levels of converting enzyme were found in the basal ganglia including caudate putamen, nucleus accumbens, globus pallidus, entopenduncular nucleus and substantia nigra pars reticulata. The neurosecretory nuclei, paraventricular nucleus and supraoptic nucleus, as well as the median eminence and posterior pituitary displayed high levels of the enzyme. In the amygdala, basolateral, lateral, basomedial, medial and anterior cortical nuclei showed moderate converting enzyme activity. The medial habenula and molecular layer of the dentate gyrus showed high levels of activity. In the cerebellum, dense labelling was observed in the Purkinje cell layer. Moderate levels of converting enzyme occurred in the gelatinosus subnucleus of the caudal part of the nucleus of the spinal tract of the trigeminal. There was a close correspondence between the distribution of angiotensin converting enzyme and angiotensin II in the neurosecretory nuclei (paraventricular and supraoptic nuclei) and median eminence and this suggests a role of angiotensin converting enzyme in the production of angiotensin II in this system. There was also a good correspondence between the distribution of angiotensin converting enzyme and angiotensin II in the subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminalis, structures abutting the anterior wall of the third ventricle which are implicated in fluid and electrolyte homeostasis. A striking discrepancy occurs in the basal ganglia which is reported to contain very little angiotensin II or angiotensin II receptors but is very rich in angiotensin converting enzyme. It is concluded that the enzyme may act to convert circulating angiotensin I to angiotensin II in circumventricular organs; generate intraneuronal angiotensin II in pathways such as the hypothalamic-hypophyseal tract; and process neuropeptides other than angiotensin II in regions such as basal ganglia.


[Management of co-morbidities in demented patients].
The interaction between co-morbidities and dementia is complex. Are co-morbidities dementia or age-related ? Does one die of dementia or with dementia ? Presentation of illness is atypical in older populations but particularly so in individuals with dementia. How should one then detect and measure the co-morbidity burden, what is the best management and the most ethically correct approach to decision making ? We will discuss basic principles that can be applied to ensure optimal care of co-morbidities in people with dementia with some practical examples.


Strategies in managing chronic pancreatitis-placement of direct percutaneous endoscopic jejunostomy feeding tubes.
Patients with chronic pancreatitis (CP) often have maldigestion and malnutrition. Nutrition support during acute and CP traditionally has been provided by parenteral nutrition. In acute pancreatitis, jejunal feeding may accelerate resolution of the inflammatory process, protect against infection, and improve outcomes at a reduced cost when compared with parenteral nutrition. Jejunal feeding may also be beneficial for patients with CP. Prolonged jejunal access may be achieved via a direct percutaneous endoscopic jejunostomy (DPEJ). This article will review the rationale and evidence for jejunal feeding, indications and contraindictions for DPEJ placement, and the technique and outcomes of DPEJ in patients with CP.


Prediction of red blood cell transfusion after orthopedic surgery using an interpretable machine learning framework.
Postoperative red blood cell (RBC) transfusion is widely used during the perioperative period but is often associated with a high risk of infection and complications. However, prediction models for RBC transfusion in patients with orthopedic surgery have not yet been developed. We aimed to identify predictors and constructed prediction models for RBC transfusion after orthopedic surgery using interpretable machine learning algorithms. This retrospective cohort study reviewed a total of 59,605 patients undergoing orthopedic surgery from June 2013 to January 2019 across 7 tertiary hospitals in China. Patients were randomly split into training (80%) and test subsets (20%). The feature selection method of recursive feature elimination (RFE) was used to identify an optimal feature subset from thirty preoperative variables, and six machine learning algorithms were applied to develop prediction models. The Shapley Additive exPlanations (SHAP) value was employed to evaluate the contribution of each predictor towards the prediction of postoperative RBC transfusion. For simplicity of the clinical utility, a risk score system was further established using the top risk factors identified by machine learning models. Of the 59,605 patients with orthopedic surgery, 19,921 (33.40%) underwent postoperative RBC transfusion. The CatBoost model exhibited an AUC of 0.831 (95% CI: 0.824-0.836) on the test subset, which significantly outperformed five other prediction models. The risk of RBC transfusion was associated with old age (>60 years) and low RBC count (<4.0 × 1012/L) with clear threshold effects. Extremes of BMI, low albumin, prolonged activated partial thromboplastin time, repair and plastic operations on joint structures were additional top predictors for RBC transfusion. The risk score system derived from six risk factors performed well with an AUC of 0.801 (95% CI: 0.794-0.807) on the test subset. By applying an interpretable machine learning framework in a large-scale multicenter retrospective cohort, we identified novel modifiable risk factors and developed prediction models with good performance for postoperative RBC transfusion in patients undergoing orthopedic surgery. Our findings may allow more precise identification of high-risk patients for optimal control of risk factors and achieve personalized RBC transfusion for orthopedic patients.


Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast.
Embryonic (ES) and trophoblast (TS) stem cells reflect the first, irrevocable cell fate decision in development that is reinforced by distinct epigenetic lineage barriers. Nonetheless, ES cells can seemingly acquire TS-like characteristics upon manipulation of lineage-determining transcription factors or activation of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway. Here we have interrogated the progression of reprogramming in ES cell models with regulatable Oct4 and Cdx2 transgenes or conditional Erk1/2 activation. Although trans-differentiation into TS-like cells is initiated, lineage conversion remains incomplete in all models, underpinned by the failure to demethylate a small group of TS cell genes. Forced expression of these non-reprogrammed genes improves trans-differentiation efficiency, but still fails to confer a stable TS cell phenotype. Thus, even ES cells in ground-state pluripotency cannot fully overcome the boundaries that separate the first cell lineages but retain an epigenetic memory of their ES cell origin.


Reorganization of Corticospinal Projections after Prominent Recovery of Finger Dexterity from Partial Spinal Cord Injury in Macaque Monkeys.
We investigated morphologic changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in seven macaque monkeys. All monkeys exhibited prominent recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional (n = 4) and ipsilesional (n = 3) hand area of primary motor cortex (M1) were investigated at 5-29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and bouton-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gray matter around the lesion, and terminating in ipsilesional Laminae VI/VII and IX were observed. In addition, axons and terminals from the ipsilesional M1 increased in the ipsilesional Lamina IX after recrossing the midline, which were not observed in intact monkeys. Conversely, axons originating from the ipsilesional M1 and directed toward the contralesional Lamina VII decreased. These results suggest that multiple reorganizations of the corticospinal projections to spinal segments both rostral and caudal to the lesion originating from bilateral M1 underlie a prominent recovery in long-term after spinal cord injury.


A comparison of short and long haemodialysis.
Two groups of patients treated by short (Milan) and long (Newcastle) haemodialysis were compared for incidence of symptoms and biochemical control. Short dialysis corrected urea and creatinine as well but control of potassium and phosphate were similar. The only apparent penalties to be paid by short dialysis patients were a higher incidence of itching, tingling or numbness, impairment of vibratory sense and difficulty in controlling blood pressure. The short dialysis group had higher haemoglobin and less dyspnoea, muscle weakness and dizziness after dialysis.


A Novel Dual Expression Platform for High Throughput Functional Screening of Phage Libraries in Product like Format.
High throughput screenings of single chain Fv (scFv) antibody phage display libraries are currently done as soluble scFvs produced in E.coli. Due to endotoxin contaminations from bacterial cells these preparations cannot be reliably used in mammalian cell based assays. The monovalent nature and lack of Fc in soluble scFvs prevent functional assays that are dependent on target cross linking and/or Fc functions. A convenient approach is to convert scFvs into scFv.Fc fusion proteins and express them in mammalian cell lines for screening. This approach is low throughput and is only taken after primary screening of monovalent scFvs that are expressed in bacteria. There is no platform at present that combines the benefits of both bacterial and mammalian expression system for screening phage library output. We have, therefore, developed a novel dual expression vector, called pSplice, which can be used to express scFv.Fc fusion proteins both in E.coli and mammalian cell lines. The hallmark of the vector is an engineered intron which houses the bacterial promoter and signal peptide for expression and secretion of scFv.Fc in E.coli. When the vector is transfected into a mammalian cell line, the intron is efficiently spliced out resulting in a functional operon for expression and secretion of the scFv.Fc fusion protein into the culture medium. By applying basic knowledge of mammalian introns and splisosome, we designed this vector to enable screening of phage libraries in a product like format. Like IgG, the scFv.Fc fusion protein is bi-valent for the antigen and possesses Fc effector functions. Expression in E.coli maintains the speed of the bacterial expression platform and is used to triage clones based on binding and other assays that are not sensitive to endotoxin. Triaged clones are then expressed in a mammalian cell line without the need for any additional cloning steps. Conditioned media from the mammalian cell line containing the fusion proteins are then used for different types of cell based assays. Thus this system retains the speed of the current screening system for phage libraries and adds additional functionality to it.


Comparative proteomic characterization of the sarcoplasmic proteins in the pectoralis major and supracoracoideus breast muscles in 2 chicken genotypes.
The selection processes that have resulted in broiler (meat) and leghorn (eggs) chickens have had very different effects on the pectoralis major and supracoracoideus muscles. The objective of this study, therefore, was to analyze the one-dimensional proteomic profiles of sarcoplasmic protein fractions isolated from the p. major and supracoracoideus muscles collected from 10 chicks from each genotype to compare developmental differences. The sarcoplasmic protein fraction was analyzed by SDS-PAGE. The mean band percentages were analyzed using a mixed model, with strain and muscle type as main effects. Six bands were found to be significantly different across the 2 strains. Strain differences in glycogen phosphorylase, enolase, elongation factor 1, creatine kinase, fructose-bisphosphate aldolase, and glyceraldehyde 3-phosphate-dehydrogenase suggest a genotype-specific shift in energy metabolism during breast muscle growth and development.


The fidelity of base selection by the polymerase subunit of DNA polymerase III holoenzyme.
In common with other DNA polymerases, DNA polymerase III holoenzyme of E. coli selects the biologically correct base pair with remarkable accuracy. DNA polymerase III is particularly useful for mechanistic studies because the polymerase and editing activities reside on separate subunits. To investigate the biochemical mechanism for base insertion fidelity, we have used a gel electrophoresis assay to measure kinetic parameters for the incorporation of correct and incorrect nucleotides by the polymerase (alpha) subunit of DNA polymerase III. As judged by this assay, base selection contributes a factor of roughly 10(4)-10(5) to the overall fidelity of genome duplication. The accuracy of base selection is determined mainly by the differential KM of the enzyme for correct vs. incorrect deoxynucleoside triphosphate. The misinsertion of G opposite template A is relatively efficient, comparable to that found for G opposite T. Based on a variety of other work, the G:A pair may require a special correction mechanism, possibly because of a syn-anti pairing approximating Watson-Crick geometry. We suggest that precise recognition of the equivalent geometry of the Watson-Crick base pairs may be the most critical feature for base selection.


The Pathophysiology of Delayed Cerebral Ischemia.
Subarachnoid hemorrhage (SAH) affects 30,000 people in the Unites States alone each year. Delayed cerebral ischemia occurs days after subarachnoid hemorrhage and represents a potentially treatable cause of morbidity for approximately one-third of those who survive the initial hemorrhage. While vasospasm has been traditionally linked to the development of cerebral ischemia several days after subarachnoid hemorrhage, emerging evidence reveals that delayed cerebral ischemia is part of a much more complicated post-subarachnoid hemorrhage syndrome. The development of delayed cerebral ischemia involves early arteriolar vasospasm with microthrombosis, perfusion mismatch and neurovascular uncoupling, spreading depolarizations, and inflammatory responses that begin at the time of the hemorrhage and evolve over time, culminating in cortical infarction. Large-vessel vasospasm is likely a late contributor to ongoing injury, and effective treatment for delayed cerebral ischemia will require improved detection of critical early pathophysiologic changes as well as therapeutic options that target multiple related pathways.


Impaired Regulation by IL-35 in Systemic Sclerosis.
This study investigated the role of IL-35 in systemic sclerosis (SSc) patients, focusing on CD4+ T cell response and immunomodulatory cytokine production. By comparing the cytokine levels in healthy donors (HD) and SSc patients using ELISAs, we found a significantly lower plasma IL-35 concentration in the SSc patients (52.1 ± 5.6 vs. 143 ± 11.1, p < 0.001). Notably, the IL-35 levels showed a negative correlation with TGF-β (p < 0.001) and IL-17 (p = 0.04). Assessing the IL-35R expression across cell types in the SSc patients and HDs via flow cytometry, we found higher levels on monocytes (40.7 + 5.7 vs. 20.3 ± 1.9, p < 0.001) and lower levels on CD8+ T cells (61.8 ± 9.2 vs. 83.4 ± 0.8, p < 0.05) in the SSc patients. The addition of recombinant IL-35 to stimulated peripheral blood mononuclear cells reduced the IL-17+CD4+ T cell percentage (9.0 ± 1.5 vs. 4.8 ± 0.7, p < 0.05) and increased the IL-35+CD4+ T percentage (4.1 ± 2.3 vs. 10.2 ± 0.8, p < 0.001). In a Treg:Tresponder cell Sco-culture assay with HD and SSc samples, rIL35 decreased the cell proliferation and levels of IL-17A (178.2 ± 30.5 pg/mL vs. 37.4 ± 6.4 pg/mL, p < 0.001) and TGF-β (4194 ± 777 pg/mL vs. 2413 ± 608 pg/mL, p < 0.01). Furthermore, we observed a positive correlation between the modified Rodnan skin score (mRSS) and TGF-β (p < 0.001), while there was a negative correlation between mRSS and IL-35 (p = 0.004). Interestingly, higher levels of plasmatic IL-35 were detected in individuals with limited disease compared to those with diffuse disease (60.1 ± 8.0 vs. 832.3 ± 4.1, p < 0.05). These findings suggest that IL-35 exhibits anti-inflammatory properties in SSc and it may serve as a marker for disease severity and a therapeutic target.


Clinical study of toe ulcer and necrosis of the apex of the distal phalanx in 53 cattle.
Clinical signs, causative factors, radiographic findings, type and duration of treatment or reason for killing were evaluated in 53 cattle (mean age: 5.3 years) suffering from toe ulcer and/or apical pedal bone necrosis. A total of 78 claws were affected. Four cattle suffered from a toe ulcer in one claw, 35 cattle showed osteolysis of the apex of the distal phalanx in a single claw and 14 cattle in two or three claws per cow. Overtrimming by means of a grinding disc and/or perforation of the sole was diagnosed as the major cause in 27 cattle (49%), laminitis in 30.2% and traumatic injuries in 11.3%. Radiography revealed a varying degree of osteolysis involving up to two-thirds of the pedal bone. Twenty-one cattle (39.6%) showing multiple toe disorders or involvement of one single claw with concurrent internal diseases were destroyed. In 23 cattle, the osteolytic bone was resected using a bone curette or hammer and chisel. Of these, the treatment was successful in 20 animals. The healing period ranged from 16-60 days when one claw was affected and from 43-53 days when two claws were affected. In five cattle, the digit was amputated.


Predictors of depression and anxiety during adolescence: the impact of birth weight.
A complex association has been observed between birth weight (BW) and depression/anxiety symptoms at various stages of life. The purpose of this study was to evaluate whether adolescents with low or insufficient BW were more likely to report depressive/anxiety symptoms. A cross-sectional study was conducted with 102 adolescents (40 boys and 62 girls). Our results demonstrated that the incidence of depressive symptoms was 63% in the first BW quartile and 20% in the fourth quartile. Similarly, we observed that anxiety symptoms were present in 83% of the adolescents in the first BW quartile, followed by 36% in the fourth BW quartile. After adjustment, our study identified potential risk factors that were associated with anxiety symptoms, including female gender (P=0.026) and having a BW in the first quartile (P=0.049). Moreover, the adjusted odds of having depression were 4.5 times higher in adolescents with BW in the lowest quartile (P=0.035). We also found that the incidence of depressive symptoms among females was 61% in the first BW quartile and 30% in the fourth BW quartile and that it was 67% versus 12%, respectively, among males. Finally, a model that used anxiety symptoms as the dependent variable produced similar data. Our findings suggest that a deleterious fetal environment appears to have a significant impact on psychiatric issues.


Optimal Enteral Nutrition Support Preserved Muscle Mass in Critically Ill Children.
Inflammation and immobility are the most relevant mechanisms that alter protein synthesis and increase protein breakdown. Protein catabolism is associated with morbidity and mortality in critically ill children. To demonstrate the effectiveness of the routinely used enteral nutrition support guideline in preventing muscle breakdown in critically ill children. A prospective cohort study was conducted in the pediatric intensive care unit (PICU) of a tertiary care hospital. Critically ill children (aged 1 month to 15 years) admitted to the PICU were enrolled. All patients were assessed for nutritional status and nutritional requirement. Enteral nutrition support following the guideline was initiated within the first 24 hours if no contraindication. The calorie target was defined either by direct measurement from indirect calorimetry or estimated from Schofield equation with protein target at least 1.5 g/kg/day. Anthropometric assessments and body composition measurements by bioelectrical impedance analysis (BIA) were examined at baseline and on the seventh day of the PICU admission. Sixty-three patients were enrolled in the study. The most common age group was 1-5 years old (38.1%). The length of PICU stay was 9.1 (SD = 12.7) days. Respiratory problems were the major cause of PICU admission (50.8%). Mechanical ventilation was required in 55.6% of the patients with the average duration of 6.3 (SD = 12.4) days. Undernutrition was found in 36.5% of the patients. Enteral feeding was the major route of nutrition support (95.2%). After the first week of admission, muscle mass was significantly preserved (p < 0.01). All patients received the nutrition support at their target energy and protein goal within the first week. The enteral feeding-related complication was reported in 1.6% of the patients. Protein catabolism during critically ill period can be minimized by optimal nutrition support. Nutrition practice using the enteral nutrition support guideline was effective in helping critically ill children reach their target caloric and protein intake.


[Correlations between the efficacy of thrombolytic therapy and appearance of abnormal Q waves in the early stages of acute myocardial infarction].
The purpose of this study was to determine the time course of the appearance of abnormal Q waves on the electrocardiogram (ECG) over the first 6 hrs of the symptoms of acute myocardial infarction (AMI) and to determine what implications, if any, such Q waves have for the efficacy of thrombolytic therapy. Severe myocardial ischemia can produce early QRS changes in the absence of infarction. Abnormal Q waves on the baseline ECG may not be an accurate marker or irreversibly injured myocardium. A study of 232 patients with AMI consecutively admitted to our coronary care units was carried out. Patients with previous AMI were not included. The presence and number of abnormal Q waves, as defined by Selvester, on the initial ECG was determined for each patient. The presence or absence and magnitude of ST segment elevation and depression were recorded and these data were used to estimate the left ventricular infarct size should thrombolytic therapy not be given (Aldrich score). Quantitative thallium-201 tomographic imaging was performed after a mean of 42 +/- 40 days from hospital discharge in 145 patients. In patients admitted within 1 hr of symptoms, 53% had abnormal Q waves on the initial ECG independent of the duration of symptoms before therapy (p < 0.001). Despite this finding, the presence of abnormal Q waves on the admission ECG did not eliminate the effect of thrombolytic therapy on reducing final infarct size (p < 0.001). Abnormal Q waves are a common finding early in the course of AMI. However, there is no evidence that abnormal Q waves are associated with less benefit in terms of reduction of infarct size after thrombolytic therapy.


Na+-dependent intestinal glucose absorption mechanisms and its luminal Na+ homeostasis across metamorphosis from tadpoles to frogs.
The abrupt morphological changes of the intestine during metamorphosis have been detailed in frogs. The features of intestinal metamorphosis are shortening of the intestine and remodeling of the intestinal epithelium. It is believed that the purpose of the morphological changes of the intestine is adaptation from aquatic herbivorous to carnivorous life. However, little is known about the physiological importance of these morphological changes. To elucidate the functional changes during metamorphosis, we measured luminal Na+ concentrations and Na+-dependent glucose uptake in tadpoles and adult African clawed frogs Xenopus laevis. The small intestine was isolated and divided into four segments in length, the luminal contents collected for analysis of ion concentration by ion chromatography. Phlorizin-sensitive glucose-induced short-circuit current (ΔIsc) was measured in intestinal preparations mounted in Ussing chambers. Although dietary sodium intake was extremely low in tadpoles, luminal Na+ concentration gradually increased along the proximal to the middle part of the intestine (>70 mM), and this Na+ concentration was comparable with that of carnivorous adult frogs. The increment of glucose-induced ΔIsc was observed in tadpole intestine. We also measured the ΔIsc induced by acetic acid, which is the major short-chain fatty acid produced by fermentation. The expression levels of mRNA for Na+-dependent glucose transporter 1 and tight junction protein claudin-15 in each intestinal segment was measured. These results suggest that luminal Na+ homeostasis is important and luminal Na+ is kept at a high concentration for Na+-dependent nutrient absorption mechanisms.


A different fixation of the femoral component in total knee arthroplasty may lead to preservation of femoral bone stock.
Good femoral bone stock is important for the stability of the femoral component in revision knee arthroplasty. However, the primary total knee replacement (TKR) may cause significant loss of bone stock in the distal anterior femur. Earlier stress-induced bone remodelling simulations have suggested that a completely debonded component may save bone stock in the distal anterior region. However, these simulations did not consider the fixation of a debonded implant and possible secondary effects of micromotions and osteolysis at the interface. The current study tries to combine the preservation of bone stock with adequate component fixation. Different bone remodelling simulations were performed around femoral knee components with different sizes of bonding area and different friction characteristics of the debonded area. The fixation of the femoral component with different bonding characteristics is quantified with calculated implant-bone interface stresses. The results show that a bonded femoral component with a debonded inner side of the anterior flange may significantly reduce bone resorption in the endangered distal anterior femur, without jeopardizing the fixation of the femoral implant. This effect may be obtained in vivo by using a femoral component with a highly polished inner side of the anterior flange.


Identification of the glycosylation site of the adenovirus type 5 fiber protein.
The fiber protein purified from the pool of nonincorporated viral protein after infection of cells with adenovirus type 5 exists as two forms separable by reverse-phase HPLC. As determined by mass spectrometry, this heterogeneity results from a difference in one O-linked N-acetylglucosamine (GlcNac). A western blot analysis using a monoclonal antibody directed against the GlcNac motif showed that only one of the two forms reacted with the antibody, suggesting that one form carries a single GlcNac and the other form has none. The ratio of glycosylated to nonglycosylated forms of fiber, which is about 1, is conserved in assembled viruses. After digestion of glycosylated fiber with endoproteinase GluC, isolation of the glycosylated peptide by reverse-phase HPLC, and chemical derivatization using dimethylamine, the site of glycosylation was located in the fiber shaft at serine 109 by mass spectrometry. Elimination of glycosylation by site-directed mutagenesis of fiber should help to understand the function of this postranslational modification.


Hindered intramolecular electron transfer in room-temperature ionic liquid.
Three perylene tetracarboxylic diimide (PDI) compounds, namely, N,N'- di(2-N'',N''-dimethylamino)ethylperylene-3,4:9,10-tetracarboxylic diimide (1), N,N'-di(2-N'',N''-dimethylamino)propylperylene-3,4:9,10-tetracarboxylic diimide (2), and N,N'- dicyclohexyl-1,7-pyrrolidinylperylene-3,4:9,10-tetracarboxylic diimide (3), have been designed and prepared. Their photophysical properties in room-temperature ionic liquid (RTILs) were studied by steady-state absorption and emission spectra and fluorescence lifetime measurements. The intramolecular photoinduced electron transfer from dimethylamine to PDI in 1 and 2 has been efficiently hindered because of the solvation of RTILs. A two-conformation mechanism for the PET in 1 and 2 is proposed, which explains the results of the fluorescence lifetime measurements well. The solvation of RTILs to 3 resembled that of a normal polar organic solvent with polarity larger than that of DMF.


Acorus calamus: a bio-reserve of medicinal values.
Many plants are found to possess reliable pharmacological properties and have started to attract the attention of researchers. One such holistic plant is Acorus calamus, commonly known as sweet flag, belonging to the rhizomatous family Acoraceae. The different parts of this plant, such as the leaves and rhizomes, are used traditionally in different medicinal preparations for the treatment of various ailments including arthritis, neuralgia, diarrhoea, dyspepsia, kidney and liver troubles, eczema, sinusitis, asthma, fevers, bronchitis, hair loss, and other disorders. Many reports have also appeared in mainstream scientific journals confirming its nutritional and medicinal properties. Biochemical analysis of the plant has revealed a large number of secondary metabolites that may be responsible for its rich medicinal properties. Basic scientific research has uncovered the mechanisms by which itexerts its therapeutic effects. Medicinal herbs such as A. calamus are quite promising in the recent therapeutic scenario, with a large number of people favouring remedies and health approaches that are free from the side effects often associated with synthetic chemicals. In this review, we try to summarise the ethno-medicinal uses, botanical descriptions, phytochemical constituents, and biological activity of the plant parts, as well as the molecular targets of A. calamus, which we hope will serve as a good base for further work on this plant.


beta-hydroxy-beta-methylglutaryl coenzyme A hydrolase of rat liver.
Beta-Hydroxy-beta-methylglutaryl coenzyme A hydrolase, or deacylase, (EC 220.127.116.11) is important, at least potentially, in the regulation of mammalian cholesterol synthesis. This is so for two reasons, both related to the enzyme generally regarded as rate-limiting for cholesterogenesis, namely beta-hydroxy-beta-methylglutaryl CoA reductase: (i) the hydrolase competes for the same substrate as the reductase and (ii) its end product, hydroxymethylglutamic acid, is a known inhibitor of the reductase. Consequently we have examined some of the properties of the hydrolase, as found in rat liver, after first developing a simple isotopic technique for its assay. Beta-Hydroxy-beta-methylglutaryl CoA hydrolase is both soluble and microsomal. The microsomal enzyme is inactivated by pre-incubation at 37 degree C, but not a 4 degree C, has an apparent pH optimum of approximately 7.6, and has Km and V values of 270 (microM) and 33.3 (nmol HMG/10 per mg protein), respectively, at 37 degree C. For the cytosolic enzyme the corresponding Km and V values are 830 and 111.1. From our observations it seems unlikely that beta-hydroxy-beta-methylglutaryl CoA hydrolase plays a significant role in the regulation of hepatic cholesterol synthesis since, in contrast to microsomal beta-hydroxy-beta-methylglutaryl coenzyme A reductase, we could find for the microsomal hydrolase no evidence of a diurnal rhythm of activity, no inhibition of activity by short-term cholesterol feeding and no evidence from Arrhenius-plot data for any membrane-mediated control of enzyme activity. Thus, the significance of the enzyme in mammalian systems remains unknown.


[Rhinovirus and acute respiratory infections in infants].
Human leucocytary interferon (IFN) in a concentration of 2,000 Ul/ml stops the development of 9 Rhinovirus (RV) strains. The use of serum IFN antibodies (SAIF) reverses this effect. Of 256 nasal aspirates culture negative for other respiratory viruses, 40 RV were isolated with SAIF as opposed to 19 without serum anti IFN. The frequency and some clinical aspects are emphasized in infants: 43% had bronchiolitis similar to respiratory syncytial virus (RSV) infections and atopy was frequent.


Iron and neurodegeneration in the multiple sclerosis brain.
Iron may contribute to the pathogenesis and progression of multiple sclerosis (MS) due to its accumulation in the human brain with age. Our study focused on nonheme iron distribution and the expression of the iron-related proteins ferritin, hephaestin, and ceruloplasmin in relation to oxidative damage in the brain tissue of 33 MS and 30 control cases. We performed (1) whole-genome microarrays including 4 MS and 3 control cases to analyze the expression of iron-related genes, (2) nonheme iron histochemistry, (3) immunohistochemistry for proteins of iron metabolism, and (4) quantitative analysis by digital densitometry and cell counting in regions representing different stages of lesion maturation. We found an age-related increase of iron in the white matter of controls as well as in patients with short disease duration. In chronic MS, however, there was a significant decrease of iron in the normal-appearing white matter (NAWM) corresponding with disease duration, when corrected for age. This decrease of iron in oligodendrocytes and myelin was associated with an upregulation of iron-exporting ferroxidases. In active MS lesions, iron was apparently released from dying oligodendrocytes, resulting in extracellular accumulation of iron and uptake into microglia and macrophages. Iron-containing microglia showed signs of cell degeneration. At lesion edges and within centers of lesions, iron accumulated in astrocytes and axons. Iron decreases in the NAWM of MS patients with increasing disease duration. Cellular degeneration in MS lesions leads to waves of iron liberation, which may propagate neurodegeneration together with inflammatory oxidative burst.


Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures.
Earlier studies indicate that parathyroid hormone (PTH) enhances insulin-like growth factor I (IGF-I) synthesis in primary osteoblast-enriched fetal rat cell cultures and the stimulatory effect of PTH on bone collagen synthesis is mediated at least in part by IGF-I. Cyclic AMP (cAMP) is a second messenger for signal transduction by PTH to its target cells, although calcium may also serve this function. We now demonstrate that isobutylmethylxanthine, forskolin, and dibutyryl cAMP, agents that elevate intracellular cAMP levels by discrete mechanisms, also enhanced the steady state transcript and polypeptide level of IGF-I in osteoblast-enriched cultures. The calcium ionophore ionomycin and phorbol myristate acetate did not increase IGF-I synthesis. In contrast, none of the agents tested increased the steady state transcript or polypeptide levels for IGF-II. The rat IGF-I gene is greater than 90 kilobases in length, and contains at least three promoter regions. Our present data represent the first demonstration of cAMP mediated IGF-I gene regulation and indicate the potential for preferential promoter usage for modulating IGF-I gene expression in bone.


Injection Safety Practice among Health Workers in Static Immunisation Centres in an Urban Community of Nigeria.
Immunisation injection accounts for less than one-tenth of the global total injections, and it is believed to be safer than therapeutic injections. However, reports have it that about one-third of immunisation injections are unsafe in many countries of the world including Africa. This study was conducted to determine the practice of sage immunisation injection among health workers in static immunisation centres in a urban community in Nigeria with a view to assessing the safety of immunisation injection services in the area. Pre-tested semi-structured questionnaires were administered to 102 consenting staff and observation checklist was completed for each of the 13 fixed immunisation centres in the study area. Most of the subjects 82(80.4%) had poor knowledge of safe immunisation injection and about the same number were not aware of any policy on injection safety. Injection abscess was the main health hazard of unsafe injection reported by majority 71(69.9) of the subjects while as few as 10(9.8%) mentioned needle prick as a health hazard. The common infections associated with unsafe injection listed by the subjects were abscess, HIV and Hepatitis in that order of frequency. Also, most of them 69(67.5%) felt that open burning is the ideal method of disposal of injection waste, while the actual method of disposal practised in most health facilities were mainly open burning (48%) and open dumping into an insecure pit (24%). Up to 83% of the subjects preferred the use of standard disposable syringes and needles for vaccination, but most of them (75(73.5%) confirmed that they use both sterilisable and disposable syringes and needles for vaccination in their health centres. BCG vaccine was exclusively administered using sterilised needles and syringes, while tetanus toxoid was given using disposable syringes and needles in virtually all the centres. Re-use of syringe for vaccine withdrawal and re-capping of used needles before discard were common practices observed while accidental needle stick injury was reported by about half (49%) of the subjects. Staff re-training, adequate supplies of injection equipment and provision of appropriate facilities for disposal of injection waste would go a long way to enhance safe immunisation injection practice in the area. Key words: immunisation, injection practice, injection safety.


A fine structural investigation of surface specializations and the cortical reaction in eggs of the cnidarian Bunodosoma cavernata.
Developing oocytes of the cnidarian Bunodosoma cavernata are located within the mesoglea of the mesenteries of the gastrovascular cavity. The cortex of the more mature vitellogenic oocytes contains numerous, electron-dense, membrane-bound, cortical granules. The surface of these oocytes possesses prominent radially projecting structures termed cytospines. Each cytospine has a core of microfilaments, 50-70 A in diameter, that extends basally as a rootlet through the cortical layer. During spawning, ova lacking any extraneous investments are released from the enclosing gastrodermis. As a consequence of fertilization or events associated with the earliest stages of development the ova undergo a massive cortical reaction. This reaction, which occurs during or just after release of the ova, involves extensive reorganization of the cortical layer. The cortical granule membranes and egg surface membrane fuse and vesiculate resulting in the massive discharge of granule contents. This event is accompanied by the loss of vesicular remnants of cortical ooplasm and the disruption of cytospine organization. Light and electron microscope comparisons of unreacted and reacted eggs show that the reaction results in a significant decrease in egg diameter with the oolemma of the reacted egg reorganizing in a position centripetal to its original location.


Is the level of steroid hormones in the low density lipoprotein (LDL) particles responsible for the prostaglandin I2 inhibitory potency of LDL?
In LDL fractions, isolated by ultracentrifugation, sexual hormones are detectable. LDL from male volunteers contained a significantly higher level of testosterone than LDL from female volunteers. This difference, however, is not responsible for the enhanced ability of LDL from men versus LDL from women to inhibit PGI2 formation. The importance of LDL testosterone is contradicted by the following results: Firstly, the PGI2 inhibitory potency of LDL is independent of the age of volunteers and the recentrifugation of isolated LDL fractions, but the level of testosterone is diminished with increasing age of volunteers and after recentrifugation. Secondly, LDL from hyperlipidemic men type II a did not inhibit PGI2 formation, but the level of testosterone in the LDL of these volunteers is significantly higher than in LDL from healthy men.


Aggressive periodontitis of the primary dentition associated with idiopathic immune deficiency: case report and treatment considerations.
The present case, of a child with an idiopathic immune deficiency and aggressive periodontitis in the primary dentition, serves as an example for the treatment considerations in these cases. Extraction of all the primary teeth proved to be the most adequate treatment. It allowed the child to eat properly and prevented unwanted infections that could endanger the life of the child. The newly erupted permanent teeth have been subjected to careful oral hygiene, clorhexidine topical applications, and have mild gingival inflammation and no attachment loss.


Blending online therapy into regular face-to-face therapy for depression: content, ratio and preconditions according to patients and therapists using a Delphi study.
Blending online modules into face-to-face therapy offers perspectives to enhance patient self-management and to increase the (cost-)effectiveness of therapy, while still providing the support patients need. The aim of this study was to outline optimal usage of blended care for depression, according to patients and therapists. A Delphi method was used to find consensus on suitable blended protocols (content, sequence and ratio). Phase 1 was an explorative phase, conducted in two rounds of online questionnaires, in which patients' and therapists' preferences and opinions about online psychotherapy were surveyed. In phase 2, data from phase 1 was used in face-to-face interviews with therapists to investigate how blended therapy protocols could be set up and what essential preconditions would be. Twelve therapists and nine patients completed the surveys. Blended therapy was positively perceived among all respondents, especially to enhance the self-management of patients. According to most respondents, practical therapy components (assignments, diaries and psycho-education) may be provided via online modules, while process-related components (introduction, evaluation and discussing thoughts and feelings), should be supported face-to-face. The preferred blend of online and face-to-face sessions differs between therapists and patients; most therapists prefer 75% face-to-face sessions, most patients 50 to 60%. The interviews showed that tailoring treatment to individual patients is essential in secondary mental health care, due to the complexity of their problems. The amount and ratio of online modules needs to be adjusted according to the patient's problems, skills and characteristics. Therapists themselves should also develop skills to integrate online and face-to-face sessions. Blending online and face-to-face sessions in an integrated depression therapy is viewed as a positive innovation by patients and therapists. Following a standard blended protocol, however, would be difficult in secondary mental health care. A database of online modules could provide flexibility to tailor treatment to individual patients, which asks motivation and skills of both patients and therapists. Further research is necessary to determine the (cost-)effectiveness of blended care, but this study provides starting points and preconditions to blend online and face-to-face sessions and create a treatment combining the best of both worlds.


Static electric dipole polarizabilities of An(5+/6+) and AnO2 (+/2+) (An = U, Np, and Pu) ions.
The parallel components of static electric dipole polarizabilities have been calculated for the lowest lying spin-orbit states of the penta- and hexavalent oxidation states of the actinides (An) U, Np, and Pu, in both their atomic and molecular diyl ion forms (An(5+/6+) and AnO2 (+/2+)) using the numerical finite-field technique within a four-component relativistic framework. The four-component Dirac-Hartree-Fock method formed the reference for MP2 and CCSD(T) calculations, while multireference Fock space coupled-cluster (FSCC), intermediate Hamiltonian Fock space coupled-cluster (IH-FSCC) and Kramers restricted configuration interaction (KRCI) methods were used to incorporate additional electron correlation. It is observed that electron correlation has significant (∼5 a.u.(3)) impact upon the parallel component of the polarizabilities of the diyls. To the best of our knowledge, these quantities have not been previously reported and they can serve as reference values in the determination of various electronic and response properties (for example intermolecular forces, optical properties, etc.) relevant to the nuclear fuel cycle and material science applications. The highest quality numbers for the parallel components (αzz) of the polarizability for the lowest Ω levels corresponding to the ground electronic states are (in a.u.(3)) 44.15 and 41.17 for UO2 (+) and UO2 (2+), respectively, 45.64 and 41.42 for NpO2 (+) and NpO2 (2+), respectively, and 47.15 for the PuO2 (+) ion.


Nitrate in groundwater: an isotopic multi-tracer approach.
In spite of increasing efforts to reduce nitrogen inputs into groundwater from intensive agriculture, nitrate (NO3) remains one of the major pollutants of drinking-water resources worldwide. Determining the source(s) of NO3 contamination in groundwater is an important first step for improving groundwater quality by emission control, and it is with this aim that we investigated the viability of an isotopic multi-tracer approach (delta15N, delta11B, 87Sr/86Sr), in addition to conventional hydrogeologic analysis, in two small catchments of the Arguenon watershed (Brittany, France). The main anthropogenic sources (fertilizer, sewage effluent, and hog, cattle and poultry manure) were first characterized by their specific B, N and Sr isotope signatures, and compared to those observed in the ground- and surface waters. Chemical and isotopic evidence shows that both denitrification and mixing within the watershed have the effect of buffering NO3 contamination in the groundwater. Coupled delta11B, delta15N and 87Sr/86Sr results indicate that a large part of the NO3 contamination in the Arguenon watershed originates from the spreading of animal manure, with hog manure being a major contributor. Point sources, such as sewage effluents, contribute to the NO3 budget of the two watersheds.


Formation of complex organic molecules in methanol and methanol-carbon monoxide ices exposed to ionizing radiation--a combined FTIR and reflectron time-of-flight mass spectrometry study.
The radiation induced chemical processing of methanol and methanol-carbon monoxide ices at 5.5 K exposed to ionizing radiation in the form of energetic electrons and subsequent temperature programmed desorption is reported in this study. The endogenous formation of complex organic molecules was monitored online and in situ via infrared spectroscopy in the solid state and post irradiation with temperature programmed desorption (TPD) using highly sensitive reflectron time-of-flight (ReTOF) mass spectrometry coupled with single photoionization at 10.49 eV. Infrared spectroscopic analysis of the processed ice systems resulted in the identification of simple molecules including the hydroxymethyl radical (CH2OH), formyl radical (HCO), methane (CH4), formaldehyde (H2CO), carbon dioxide (CO2), ethylene glycol (HOCH2CH2OH), glycolaldehyde (HOCH2CHO), methyl formate (HCOOCH3), and ketene (H2CCO). In addition, ReTOF mass spectrometry of subliming molecules following temperature programmed desorption definitely identified several closed shell C/H/O bearing organics including ketene (H2CCO), acetaldehyde (CH3COH), ethanol (C2H5OH), dimethyl ether (CH3OCH3), glyoxal (HCOCOH), glycolaldehyde (HOCH2CHO), ethene-1,2-diol (HOCHCHOH), ethylene glycol (HOCH2CH2OH), methoxy methanol (CH3OCH2OH) and glycerol (CH2OHCHOHCH2OH) in the processed ice systems. Additionally, an abundant amount of molecules yet to be specifically identified were observed sublimating from the irradiated ices including isomers with the formula C3H(x=4,6,8)O, C4H(x=8,10)O, C3H(x=4,6,8)O2, C4H(x=6,8)O2, C3H(x=4,6)O3, C4H8O3, C4H(x=4,6,8)O4, C5H(x=6,8)O4 and C5H(x=6,8)O5. The last group of molecules containing four to five oxygen atoms observed sublimating from the processed ice samples include an astrobiologically important class of sugars relevant to RNA, phospholipids and energy storage. Experiments are currently being designed to elucidate their chemical structure. In addition, several reaction pathways were identified in the irradiated ices of mixed isotopes based upon the results of both in situ FTIR analysis and TPD ReTOF gas phase analysis. In general, the results of this study provide crucial information on the formation of a variety of classes of organics including alcohols, ketones, aldehydes, esters, ethers, and sugars within the bulk ices upon exposure to ionizing radiation that are relevant to the molecular clouds within the interstellar medium.