Focal status epilepticus as atypical presentation of pyridoxine-dependent epilepsy.
Pyridoxine-dependent epilepsy usually presents in the neonatal period or even in utero, is refractory to antiepileptic medications, and is treatable with lifelong administration of pyridoxine. The seizures are typically generalized tonic-clonic, although myoclonic seizures or infantile spasms have been described. We report an infant who presented at 5 months of age with a right-sided clonic seizure with fever. Subsequently, she had recurrent right focal or generalized seizures despite sequential treatment with various antiepileptic medications. At 7 months, she was hospitalized with status epilepticus, which was finally controlled with pyridoxine. After she became seizure free, she continued to have a strong left arm preference with mild weakness of the right arm and delayed language skill. Eventually, she outgrew these symptoms. This case illustrates that pyridoxine-dependent epilepsy, although rare, must be included in the differential diagnosis of focal seizures, especially when the seizures are refractory to traditional antiepileptic drugs.


Protein binding of valproic acid in Japanese pediatric and adult patients with epilepsy.
The binding of valproic acid to serum proteins in pediatric and adult patients was studied. Serum samples were obtained from 48 Japanese pediatric patients with epilepsy (group A) and 48 Japanese adult patients with epilepsy (group B) receiving valproic acid monotherapy. The patients' age ranged from 1 to 15 years for the pediatric patients and from 18 to 44 years (group B--younger) and 45 to 63 years (group B--older) for the adult patients. The serum concentrations of total and unbound valproic acid were measured by fluorescence polarization immunoassay, and the unbound serum fraction of valproic acid was analyzed by ultrafiltration. The mean association constant, K, and total concentration of binding sites, n(P), were as follows: group A, K = 0.016 L/mumol, n(P) = 1077 microM; group B, K = 0.011 L/mumol, n(P) = 1365 microM; group B--younger, K = 0.013 L/mumol, n(P) = 1291 microM; and group B--older, K = 0.006 L/mumol, n(P) = 1827 microM. Significant differences between groups A and B were observed in the serum free fatty acid concentration and the serum concentration ratio of free fatty acids to albumin. However, no significant differences between the two groups were observed in the binding of valproic acid to serum proteins. Group A's serum concentration ratio of free fatty acids to albumin was significantly lower than in group B--older and was lower than in group B--younger. However, there were no significant differences in binding between group A and groups B--younger and B--older. The serum concentration of albumin was significantly higher in group B--younger than in group B--older. Consequently, there was a significant difference in binding between groups B--younger and B--older. The serum protein binding of valproic acid was similar in pediatric and adult patients with epilepsy, but binding characteristics differed between younger and older adults.


Developing a research unit within a hospital social work department.
This article describes the establishment of a research unit as an integral part of a hospital social work department on the basis of the authors' experience in a cancer center over a 13-year period. Methods are described for building support within the institution, for the process of initiating the unit, for deciding on study topics, and finally for bridging the gap between clinical and research staff. The evolution of the relationship between clinical and research staff was characterized by four different phases: curiosity, competitiveness, cooperation, and collaboration. A childhood bereavement project is used to exemplify the developmental processes and the ongoing interaction of research and clinical staff. The professional practice of all staff benefited from the increased academic rigor and productivity, although some staff remained unconvinced of the value of such a major research effort. The benefits and costs of the unit are also discussed.


[A preliminary analysis on potentially targeted genes of induced chemotherapy in supraglottic laryngeal squamous cell carcinoma].
To analyze the differentially expressed genes produced by paclitaxel, cisplatin and 5-fluorouracil(TPF) regimen induction chemotherapy and the potentially functionally targeted genes of the induced chemotherapy in supraglottic laryngeal squamous cell carcinoma. A total of 11 tissue samples from patients diagnosed as supraglottic carcinoma who didn't receive any treatment before were analyzed with microarray. The patients were divided into two groups based on their responses to the induction chemotherapy: 7 were sensitive to chemotherapy and 4 were non-sensitive. Gene expressions were detected by Illumina Human HT-12 BeadChip. The bioinformatics analysis online was used to analyze the differentially expressed genes. A total of 1 554 differentially expressed genes related to chemosensitivity were found. Analyzed with GO database, the up-regulated genes included the functional sets of biological adhesion, immune system development and stem cell proliferation, and the down-regulated genes included the functional sets of cell junction organization, phosphorus metabolic process and cell morphogenesis involved in differentiation. Analyzed with KEGG database, the up-regulated pathways included p53, cell adhesion and Ras signaling pathways, and the down-regulated pathways included focal adhesion, endocytosis and ErbB signaling pathways. There were statistically significant differences in the expressions of MAPK10, PIK3R5 and JUN genes, which had biological significance, between sensitive patients and non-sensitive patients. MAPK10, PIK3R5 and JUN may be considered as potentially functional genes of the induced chemotherapy in supraglottic carcinoma.


Semiclassical treatments for small-molecule dynamics in low-temperature crystals using fixed and adiabatic vibrational bases.
Time-resolved coherent nonlinear optical experiments on small molecules in low-temperature host crystals are exposing valuable information on quantum mechanical dynamics in condensed media. We make use of generic features of these systems to frame two simple, comprehensive theories that will enable the efficient calculations of their ultrafast spectroscopic signals and support their interpretation in terms of the underlying chemical dynamics. Without resorting to a simple harmonic analysis, both treatments rely on the identification of normal coordinates to unambiguously partition the well-structured guest-host complex into a system and a bath. Both approaches expand the overall wave function as a sum of product states between fully anharmonic vibrational basis states for the system and approximate Gaussian wave packets for the bath degrees of freedom. The theories exploit the fact that ultrafast experiments typically drive large-amplitude motion in a few intermolecular degrees of freedom of higher frequency than the crystal phonons, while these intramolecular vibrations indirectly induce smaller-amplitude--but still perhaps coherent--motion among the lattice modes. The equations of motion for the time-dependent parameters of the bath wave packets are fairly compact in a fixed vibrational basis/Gaussian bath (FVB/GB) approach. An alternative adiabatic vibrational basis/Gaussian bath (AVB/GB) treatment leads to more complicated equations of motion involving adiabatic and nonadiabatic vector potentials. Computational demands for propagation of the parameter equations of motion appear quite manageable for tens or hundreds of atoms and scale similarly with system size in the two cases. Because of the time-scale separation between intermolecular and lattice vibrations, the AVB/GB theory may in some instances require fewer vibrational basis states than the FVB/GB approach. Either framework should enable practical first-principles calculations of nonlinear optical signals from molecules in cryogenic matrices and their semiclassical interpretation in terms of electronic and vibrational decoherence and vibrational population relaxation, all within a pure-state description of the macroscopic many-body complex.


Role of fluorine-18 fluorodeoxyglucose positron emission tomography in a case of renal cell carcinoma to differentiate tumor thrombus from bland thrombus.
Tumor thrombus is a rare complication of many solid tumors. We present a case of renal cell carcinoma whose baseline contrast-enhanced computerized tomography (CT) revealed an heterogeneously enhancing mass in the upper half of right kidney with tumor thrombus in the right renal vein extending to suprarenal inferior vena cava (IVC), crossing the cavoatrial junction and reaching up to the right atrium (Grade IV). Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT imaging revealed large irregular right renal mass, hypermetabolic tumor thrombus extending from the right renal vein to suprarenal IVC reaching up to the right atrium. There was no FDG uptake noted in the infrarenal IVC and bilateral iliofemoral venous thrombi. Thus, 18F-FDG PET/CT was not only helpful in the staging, but was also helpful in differentiating tumor thrombus from bland thrombus in our patient.


The application of eDNA for monitoring of the Great Crested Newt in the UK.
Current ecological surveys for great crested newts are time-consuming and expensive and can only be carried out within a short survey window. Additional survey methods which would facilitate the detection of rare or protected species such as the great crested newt (Triturus cristatus) would be extremely advantageous. Environmental DNA (eDNA) analysis has been utilized for the detection of great crested newts in Denmark. Here, the same methodology has been applied to water samples taken from UK ponds concurrently with conventional field surveying techniques. Our eDNA analysis exhibited an 84% success rate with a kappa coefficient of agreement between field and eDNA surveys of 0.86. One pond determined to be negative for great crested newt by field survey was positive by eDNA analysis, revealing the potential for improved detection rates using this methodology. Analysis of water samples collected in late summer indicates that eDNA analysis could be used to detect great crested newt after the optimal survey window for current field techniques had passed. Consequently, eDNA analysis could augment currently stipulated techniques for great crested newt surveying as a relatively quick and inexpensive tool for collecting great crested newt presence and distribution data within the UK instead of or prior to full field surveys.


Digoxigenin-labeled probe-based colony blotting assay for rapid quantification of Salmonella serovars in seafood and water.
A non-radio-labeled probe-based detection method was developed for rapid enumeration of Salmonella in seafood and water samples. A Salmonella-specific invA gene probe was developed using a digoxigenin-based non-radio labeling assay, which was evaluated with naturally contaminated seafood and water samples. The probe-based technique was further compared with the quantitative PCR assay. The method was specific for detection of different Salmonella serovars without any nonspecific hybridization with other Salmonella-related Enterobacteriaceae. The optimum labeling efficiency was determined for the labeled probe, and 10 pg/microL probe concentration was observed to be most efficient for detection of Salmonella colonies on nylon membrane. Quantification of Salmonella in naturally contaminated seafood and water samples (n = 21) was in the range 10-10(2) CFU/mL. The assay successfully quantified Salmonella in spiked seafood and water samples in the presence of background flora, and the entire assay was completed within 48 h. The probe-based assay was further evaluated with real-time PCR, and results showed that the assay was comparable to real-time PCR assay. Thus, this probe-based assay can be a rapid, useful, and alternative technique for quantitative detection of Salmonella in food, feed, and water samples.


[Expression of CD(59) and CD(45) on lymphocytes in paroxysmal nocturnal hemoglobinuria patients].
To analyse the expression of glycosylphosphatidylinositol (GPI)-anchored protein and functional transition of lymphocyte subsets in paroxysmal nocturnal hemoglobinuria (PNH) patients. Flow cytometer and multi-color McAbs were used to detect CD(59) expression on lymphocytes and their subsets. Stimulation test was used to examine the ability of affected T cells in converting from CD(45RA) phenotype to CD(45RO) phenotype. In 14 PNH samples, CD(59) expression on affected lymphocytes was at a lower percentage than that on granulocytes and erythrocytes. B lymphocytes were widely affected than NK or T cells. CD(59)(-) deficient B lymphocytes existed in all PNH patients. More CD(8)(+) T cells were affected than CD(4)(+) T cells. Expression of HLA-DR and CD(45RO) on affected T cells were significantly lower than that on normal T cells (P < 0.01), whereas the expression of CD(45RA) was much higher on the former (P < 0.01). After stimulation with phytohemagglutinin (PHA), the expression of CD(45RA)(+) on affected T cells decreased sharply (the median value was from 82.7% to 26.6%), while the expression of CD(45RO)(+) increased significantly (the median value was from 19.6% to 64.3%). The deficient CD(59) phenotype does involve in the different types of lymphocytes in PNH patients. Therefore affected B cells could be a good marker for diagnosis of PNH. The affected T cells were mainly comprised naive cells (CD(45RA)(+)HLA-DR(-)), which could acquire the memory phenotype (CD(45RO)(+)HLA-DR(+)) after stimulated by antigen.


Information management strategies in early adolescence: developmental change in use and transactional associations with psychological adjustment.
Adolescents use various strategies to manage their parents' access to information. This study tested developmental change in strategy use, longitudinal associations between disclosing and concealing strategies, and longitudinal associations linking disclosing and concealing strategies with antisocial behavior and depressive symptoms. Self-report data (n = 218; 49% female; 49% European American, 47% African American) following Grades 5 (M age = 11 years, 11 months), 6, and 7 show that the use of disclosing strategies (e.g., telling all, telling if asked) following misbehavior declined while use of concealing strategies (e.g., omitting details, keeping secrets, lying) increased over time. Longitudinal links between strategies suggest a transactional process wherein infrequent disclosing is a gateway to concealment but concealment also predicts subsequent rank-order reductions in disclosure. Infrequent disclosing was associated with more subsequent antisocial behavior and depressive symptoms, whereas more antisocial behavior was associated with more subsequent concealment. Although absolute declines in disclosure and increases in concealment are normative, individual differences show that adolescents reporting low levels of disclosure, rather than high levels of concealment, appear to experience the most adjustment problems.


Vegetable and fruit intakes of on-reserve first nations schoolchildren compared to Canadian averages and current recommendations.
This study investigated, in on-reserve First Nations (FN) youth in Ontario, Canada, the following: (a) the intakes of vegetable and fruit, "other" foods and relevant nutrients as compared to current recommendations and national averages, (b) current prevalence rates of overweight and obesity and (c) the relationship between latitude and dietary intakes. Twenty-four-hour diet recalls were collected via the Waterloo Web-Based Eating Behaviour Questionnaire (WEB-Q) (n = 443). Heights and weights of participants were self reported using measured values and Body Mass Index was categorized using the International Obesity Task Force cutoffs. Food group and nutrient intakes were compared to current standards, Southern Ontario Food Behaviour data and the Canadian Community Health Survey, Cycle 2.2, using descriptive statistics. Mean vegetable and fruit, fibre and folate intakes were less than current recommendations. Girls aged 14-18 years had mean intakes of vitamin A below current recommendations for this sub-group; for all sub-groups, mean intakes of vegetables and fruit were below Canadian averages. All sub-groups also had intakes of all nutrients and food groups investigated that were less than those observed in non-FN youth from Southern Ontario, with the exception of "other" foods in boys 12-18 years. Prevalence rates of overweight and obesity were 31.8% and 19.6%, respectively, exceeding rates in the general population. Dietary intakes did not vary consistently by latitude (n = 248), as revealed by ANOVA. This study provided a unique investigation of the dietary intakes of on-reserve FN youth in Ontario and revealed poor intakes of vegetables and fruit and related nutrients and high intakes of "other" foods. Prevalence rates of overweight and obesity exceed those of the general population.


Infective endocarditis (IE) in children receiving treatment for cancer.
Infective endocarditis (IE) is rare in children but is associated with substantial morbidity/mortality. Medical records of 161 new patients admitted to the Pediatric Oncology Unit in a 2 years period were reviewed to identify patients with a diagnosis of IE following the Duke criteria. Nine patients developed IE; their ages ranged from 2.4 to 11.3 years. The patients received treatment according to the results of blood cultures. TIPs are associated with a high rate of IE. The diagnosis of IE should be considered in children with cancer who have major/minor criteria as defined by the Duke criteria.


Characterization of a Single Genomic Locus Encoding the Clustered Protocadherin Receptor Diversity in Xenopus tropicalis.
Clustered protocadherins (cPcdhs) constitute the largest subgroup of the cadherin superfamily, and in mammals are grouped into clusters of α-, β-, and γ-types. Tens of tandemly arranged paralogous Pcdh genes of the Pcdh clusters generate a substantial diversity of receptor isoforms. cPcdhs are known to have important roles in neuronal development, and genetic alterations of cPcdhs have been found to be associated with several neurological diseases. Here, we present a first characterization of cPcdhs in Xenopus tropicalis We determined and annotated all cPcdh isoforms, revealing that they are present in a single chromosomal locus. We validated a total of 96 isoforms, which we show are organized in three distinct clusters. The X. tropicalis cPcdh locus is composed of one α- and two distinct γ-Pcdh clusters (pcdh-γ1 and pcdh-γ2). Bioinformatics analyses assisted by genomic BAC clone sequencing showed that the X. tropicalis α- and γ-Pcdhs are conserved at the cluster level, but, unlike mammals, X. tropicalis does not contain a β-Pcdh cluster. In contrast, the number of γ-Pcdh isoforms has expanded, possibly due to lineage-specific gene duplications. Interestingly, the number of X. tropicalis α-Pcdhs is identical between X. tropicalis and mouse. Moreover, we find highly conserved as well as novel promoter elements potentially involved in regulating the cluster-specific expression of cPcdh isoforms. This study provides important information for the understanding of the evolutionary history of cPcdh genes and future mechanistic studies. It provides an annotated X. tropicalis cPcdh genomic map and a first molecular characterization essential for functional and comparative studies.


The myelodysplastic syndrome: prognostic factors in relation to the "in vitro" clonogenic assay.
The object of this study was to determine whether the "in vitro" parameters of medullary and blood granulopoiesis in patients with MDS, furnish information of either prognostic or diagnostic value. This study covered 94 patients with MDS. All patients were studied at the onset of disease. In order to identify the factors related to patients' survival, Cox Multiple Regression analysis was performed by the BMD P2L program. When analyzing by means of actuarial curves the survival probability of patients with benign development versus those of malignant development (those who developed ANLL), the significance between both groups was p = 0.0001. Different variables of patients included in this study were analyzed and all showed great significances. Fab: p = 0.0022, disease evolution: p = 0.0001 and presence of blastic aggregates: p = 0.0011. Cox's regression analysis revealed that the only predictable survival variable is the presence of blastic colonies and/or clusters. Accordingly, two groups were constructed: favourable and unfavourable. In the favourable group, 40% of the patients belonged to the RA group, while in the unfavourable group, 55% belonged to the RAEB group. This study shows the validity of the elaboration of prognostic groups in MDS according to the presence of blastic colonies and/or clusters in CFUGM medullary and/or peripheral cultures. The "in vitro" myeloid progenitors culture techniques may therefore be advantageously applied in these disorders for formulating a diagnosis and predicting the patient's short term evolution.


Physical activity and the risk of acute myocardial infarction. GISSI-EFRIM Investigators. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-Epidemiologia dei Fattori di Rischio dell'Infarto Miocardico.
The relationship between physical activity and acute myocardial infarction (AMI) was examined in a case-control study conducted in Italy in 1988 to 1989 within the framework of the GISSI-2 trial of streptokinase versus alteplase and heparin versus no heparin in the treatment of AMI. A total of 916 case patients admitted to coronary care units from various Italian regions for AMI were interviewed. Control subjects were 1106 patients admitted to the same network of hospitals for a broad spectrum of acute diseases not related to known or potential risk factors for myocardial infarction. Among various types of physical activity (occupational activity, walking, stair climbing, and sport and leisure-time physical activity), occupational physical exercise emerged as the most protective. Multivariate odds ratios (ORs) were 1.4 (95% confidence interval (CI), 1.0 to 2.0) and 1.6 (95% CI, 1.2 to 2.1) for the two lowest levels of occupational physical activity. The trends of increasing risk with decreasing activity were consistent, although less strong, when other types of activity were considered. The protection conveyed by occupational physical activity was similar across various strata of sex, age, education, smoking habits, and diabetes, and was not explained by serum cholesterol, body weight, or hypertension. This study therefore confirms that low physical activity is an indicator of subsequent risk of AMI.


Upregulation of MTA1 in Colon Cancer Drives A CD8+ T Cell-Rich But Classical Macrophage-Lacking Immunosuppressive Tumor Microenvironment.
The MTA1 protein encoded by metastasis-associated protein 1 (MTA1) is a key component of the ATP-dependent nucleosome remodeling and deacetylase (NuRD) complex, which is widely upregulated in cancers. MTA1 extensively affects downstream gene expression by participating in chromatin remodeling. Although it was defined as a metastasis-associated gene in first reports and metastasis is a process prominently affected by the tumor microenvironment, whether it affects the microenvironment has not been investigated. In our study, we elucidated the regulatory effect of MTA1 on tumor-associated macrophages (TAMs) and how this regulation affects the antitumor effect of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment of colorectal cancer. We detected the cytokines affected by MTA1 expression via a cytokine antibody array in control HCT116 cells and HCT116 cells overexpressing MTA1. Multiplex IHC staining was conducted on a colorectal cancer tissue array from our cancer cohort. Flow cytometry (FCM) was performed to explore the polarization of macrophages in the coculture system and the antitumor killing effect of CTLs in the coculture system. Bioinformatics analysis was conducted to analyze the Cancer Genome Atlas (TCGA) colorectal cancer cohort and single-cell RNA-seq data to assess the immune infiltration status of the TCGA colorectal cancer cohort and the functions of myeloid cells. MTA1 upregulation in colorectal cancer was found to drive an immunosuppressive tumor microenvironment. In the tumor microenvironment of MTA1-upregulated colorectal cancer, although CD8+ T cells were significantly enriched, macrophages were significantly decreased, which impaired the CTL effect of the CD8+ T cells on tumor cells. Moreover, upregulated MTA1 in tumor cells significantly induced infiltrated macrophages into tumor-associated macrophage phenotypes and further weakened the cytotoxic effect of CD8+ T cells. Upregulation of MTA1 in colorectal cancer drives an immunosuppressive tumor microenvironment by decreasing the microphages from the tumor and inducing the residual macrophages into tumor-associated microphage phenotypes to block the activation of the killing CTL, which contributes to cancer progression.


Transient increase of serum IgD levels after allogeneic bone-marrow transplantation.
Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation.


[Mycobacterial infection in patients with AIDS].
Bacteriological diagnosis of tuberculosis was performed in 104 HIV-positive patients, in majority AIDS patients hospitalized in AIDS Clinic of Infections and Parasitic Diseases Institute of Medical Academy. 390 samples were examined, e.d. 3.75 from each patient (from 1 to 22 samples). M. Tuberculosis was diagnosed in 14 patients and all of them were clinically observed because of pulmonary tuberculosis. The highest percentage of positive results was obtained from bronchial fluid evacuated during bronchoscopy.


Flow injection on-line sorption preconcentration coupled with hydride generation atomic fluorescence spectrometry for determination of (ultra)trace amounts of arsenic(III) and arsenic(V) in natural water samples.
A flow injection on-line sorption preconcentration and separation in a knotted reactor (KR) was coupled to hydride generation atomic fluorescence spectrometry (HG-AFS) for speciation of inorganic arsenic in natural water samples. The method involved on-line formation of the As(III)-pyrrolidinedithiocarbamate (PDC) complex over a sample acidity of 0.001-0.1 mol L(-1) HCl, its adsorption onto the inner walls of the KR made from 150-cm long x 0.5-mm i.d. PTFE tubing, elution withmol L(-1) HCl, and detection by HG-AFS. Total inorganic arsenic was determined after prereduction of As(V) to As(III) with 1% m/v L-cysteine. The concentration of As(V) was calculated by the difference of the total inorganic arsenic and As(III). A 1 mol L(-1) concentration of HCl was employed not only as the efficient eluent but also as the required medium for subsequent hydride generation. Potential factors that affect adsorption, rinsing, elution, and hydride generation were investigated in detail. The low cost, easy operation, and high sensitivity are the obvious advantages of the present system. With consumption of a 6 mL sample solution, an enhancement factor of 11 and a detection limit (3s) of 0.023 microg L(-1) As(III) were obtained at a sample throughput of 32 h(-1). The precision for 14 replicate measurements of 1 microg L(-1) As(III) was 1.3% (RSD). The recoveries from natural water samples varied from 96.7 to 105% for 2 microg L(-1) of As(III) spike and from 97.1 to 107% for 2 microg L(-1) of As(V) spike. The analytical results obtained by the present method for total arsenic in the certified reference materials, SLRS-4 (river water) and NASS-5 (seawater), agreed well with the certified values. The developed method was also successfully applied to the speciation of inorganic arsenic in local natural water samples.


Functional analysis of the complex trans-activating response element RNA structure in simian immunodeficiency virus.
Transcription of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is activated through binding of the viral Tat protein to the trans-activating response (TAR) element at the 5' end of the nascent transcript. Whereas HIV type 1 (HIV-1) TAR folds a simple hairpin structure, the corresponding domains of HIV-2 and SIVmac exhibit a more complex structure composed of three stem-loops. This structural polymorphism may be attributed to additional functions of TAR in HIV-2/SIVmac replication. We recently constructed an SIVmac variant that does not require the Tat-TAR interaction for transcription. We used this variant to study additional roles of TAR in SIVmac replication and generated mutants with a truncated TAR structure. We demonstrate that partial or nearly complete removal of TAR does not impair viral transcription, RNA processing, and translation. Moreover, these deletions do not significantly affect virus replication in the PM1 T-cell line and macaque peripheral blood mononuclear cells. These results demonstrate that the complex TAR structure in SIVmac has no other essential function in virus replication in vitro besides its role in Tat-mediated activation of transcription.


Defending definitions of life.
Over the past 10 years, it has become unpopular to talk about definitions of life, under the assumption that attempts at a precise definition are counterproductive. Recent attempts have failed to meet strict philosophical criteria for definitions and have failed to reach consensus. I argue that provisional definitions are necessary for clear communications. Our current knowledge of biology justifies a number of universal claims about the category of life. Whether or not "life" represents a natural category, it maps to a number of important, observable processes. Given the importance of those processes and the extent of our knowledge, plural explicit definitions of life (and related categories) will be necessary for progress in astrobiology and origin-of-life studies as well as biology in general. I propose concrete categories related to, but not necessarily coextensive with, life for clear communication and hypothesis formation: Woese life, Darwin life, Haldane life.


AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6.
Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1 beta, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, we examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. We found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [3H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at greater than 10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. The decrease from IL-6 antisense in AIDS-KS cell proliferation was reversed by the addition of hrIL-6. We confirmed that AIDS-KS cells produced IL-6 in vivo by preparing RNA and tissue sections from involved and uninvolved skin from a patient with AIDS Kaposi sarcoma. We detected immunoreactive IL-6 in the involved tumor areas and to a lesser extent in the surrounding normal epidermis. Slot blot hybridization showed a great excess of IL-6 and IL-6-R RNA in involved skin compared to uninvolved skin. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells.


Isolation and characterization of rhesus monkey milk lactoferrin.
Rhesus monkey milk lactoferrin was isolated and its characteristics compared with those of human milk lactoferrin in order to assess the feasibility of using the rhesus monkey as an animal model for the study of iron absorption from milk. Monkey lactoferrin was isolated from pooled monkey milk by two chromatographic steps. Concentration of lactoferrin in milk, determined by rocket immunoelectrophoresis, demonstrated similar concentrations in both human and monkey milk, 1-2 mg/ml. Immunodiffusion of lactoferrins from several species using an antibody raised to money lactoferrin resulted in a cross-reaction only with monkey and human lactoferrin. Lactoferrins from cow, sheep, goat, dog, and rat milk were not recognized by the antibody. Amino acid analysis of monkey lactoferrin showed a composition very similar to human lactoferrin, as well as a similarity in the unusual amino acid sequence at the N-terminal of the protein. The carbohydrate moiety of monkey lactoferrin was investigated and shown to contain monosaccharides in similar proportions to those reported for human lactoferrin. In our opinion, the rhesus monkey is a promising model for the study of the role of lactoferrin in iron absorption in the infant, as well as of the other proposed actions of lactoferrin.


Decentralization and public delivery of health care services in India.
This paper examines delivery of public health care services in India, in the broader context of decentralization. It provides an overview of the basic features and recent developments in intergovernmental fiscal relations and accountability mechanisms, and it examines the implications of these institutions for the quality of public service delivery. It then addresses recent policy proposals on the public provision of health care, in the context of decentralization. Finally, it makes suggestions for reform priorities to improve public health care delivery.


Race and ethnic variation in proximal femur structure and BMD among older men.
Femoral neck dimensions and vBMD from QCT were compared among 3,305 black, Asian, Hispanic, and white men >or=65 yr of age. All had similar stature-adjusted mean femoral neck volume, but black and Asian men had thicker cortices and higher trabecular vBMD, which may increase bone strength. Hip fracture rates among elderly U.S. black and Asian men are lower than rates among white men. Structural characteristics or volumetric BMD (vBMD), which confer advantages for femoral neck bone strength, may vary by race/ethnicity. However, this topic has not been studied in detail. In a cross-sectional study, dimensions and vBMD in the femoral neck and shaft were obtained from QCT scans among 3,305 men >or=65 yr of age in the Osteoporotic Fractures in Men (MrOS) study. Femoral neck measures were cross-sectional area; integral, cortical, and medullary volumes and integral, cortical, and trabecular vBMD. Shaft measures were cross-sectional, cortical, and medullary areas and cortical vBMD. Self-reported race/ethnicity was classified as black, Asian, Hispanic, or white. We used multivariable linear regression models with adjustment for age, height, and body mass index to compare means of the outcome measures in black, Asian, and Hispanic men to those in whites. All groups had similar femoral neck integral volume. Among black and Asian men, mean cortical volume as a percent of integral volume was 6% greater, integral vBMD was 6-10% greater, and trabecular vBMD was 33-36% greater than means among whites. Shaft cross-sectional area was similar among blacks, but smaller among Asians, compared with whites. However, mean shaft cortical area was greater among blacks but similar among Asians and whites, resulting in mean cortical thickness being 5% greater among black and Asian men. Blacks also had greater mean cortical vBMD in both the femoral neck and shaft. Black and Asian men >or=65 yr of age have features in the proximal femur that may confer advantages for bone strength. Specifically, greater cortical thickness and higher trabecular vBMD among black and Asian men could help explain the lower hip fracture rates in these populations. Discerning the mechanisms underlying these differences could provide advances for the prevention and treatment of osteoporosis.


[Selecting variants of drug treatment of non-complicated duodenal ulcer (based on a study of results of Rabeprazole efficiency)].
This article presents considerations currently under discussion about the probability of HP participation in the ulcer causation as well as information about Rabeprazole efficiency for anti-helicobacter therapy of non-complicated duodenal ulcer (as a result of 7-day anti-helicobacter therapy, the healing of duodenal bulbs was recorded in 82.6% of cases; HP eradication was recorded in 86.9% of cases 4 weeks after the termination of the treatment) based on the analysis of scientific literature data and personal experience. Considerations related to the conduction of a possible study in the field of ulcer therapy that is not associated with Helicobacter pylori are presented.


Conventional vs. formulated foods in school lunches. II. Cost of food served, eaten, and wasted.
School lunches containing all conventional foods were designed to provide one-third or one-half the recommended allowances for elementary students. The same nutrient levels were planned in meals containing some formulated items. Each type of meal was served for five days, and total food costs and costs of food served, consumed, and wasted were calculated. At the same nutritional level, mean preparation costs of partially formulated meals were lower than for meals composed of all conventional foods. Meals providing one-half the allowances and containing formulated items cost slightly less than totally conventional meals which provided one-third of the allowances. Cost of waste was lower with partially formulated meals.


Peliosis hepatis and systemic lupus erythematosus: A rare condition identified by magnetic resonance imaging.
Peliosis hepatis is a rare benign disorder characterized by the presence of multiple cavities filled with blood with no preferential localization in the liver parenchyma. It may be related to several etiologic conditions, especially infections and toxicity of immunosuppressive drugs. To our knowledge, there are only three articles reporting the association between peliosis hepatis and systemic lupus erythematosus. In this report, we describe a case of this rare condition, highlighting the importance of magnetic resonance imaging. A short review of this subject is also presented.


Study of the effects of cicletanine on the renin-angiotensin-aldosterone system.
The effect of a single dose of 50 mg of cicletanine on plasma renin activity, plasma potassium and aldosterone, blood pressure, urinary volume and sodium and potassium excretion was compared to the effect of the same dose given for 9 days in eight normal volunteers in metabolic balance on 120-140 mEq of sodium and 50-70 mEq potassium. Following 4 days of this standardized diet, the normal volunteers received their first dose of cicletanine after an overnight fast and blood was collected at 30 min, 2, 4 and 6 h for plasma renin activity and aldosterone. Urine excreted following a modest water load was also collected and analysed over a 6-h period. Following the single dose there was an increase in PRA at 1 and 2 h, while there was no such increase with chronic administration. Plasma aldosterone, however, showed no difference between acute and chronic administration of cicletanine treatment. Also plasma uric acid levels increased with acute but not chronic cicletanine. There were no differences in heart rate and blood pressure responses, nor in urine volume, urinary sodium or potassium excretion, or plasma potassium between the different treatments. This study strongly suggests that the antihypertensive effect of cicletanine is not the result of an increased diuresis, as in this case enhanced urinary electrolyte excretion and increased plasma renin activity and aldosterone would be mandatory following chronic administration. Recent evidence suggests that the dissociation between plasma renin activity and aldosterone is the consequence of an effect of cicletanine on intracellular calcium mobilization. This mode of action would explain both the antihypertensive as well as the aldosterone secretion reducing effect of cicletanine.


[Do short-term duration drugs for anaesthesia give postoperative advantages compared to traditional drugs?].
We wanted to compare totally intravenous anaesthesia with propofol and remifentanil to mixed anaesthesia with isoflurane and fentanyl in terms of postoperative pain, nausea, length of stay and costs. We present a prospective, non-randomised, anaesthetist-based double-blind study with a cost-utility analysis on consecutive patients undergoing laparoscopic gynaecologic day-care surgery. Premedication consisted of paracetamol and diclofenac. The mixed anaesthesia group received propofol, isoflurane, fentanyl, vecuronium, N2O and O2,the total intravenous group propofol, remifentanil, vecuronium, N2O and O2. Paracetamol and ketobemidon, metoklopramid and ondansetron were given to relieve pain and nausea, respectively. Patients were asked to report pain and nausea on a visual analogue scale after 4 and 24 hours. 26 mixed and 27 totally intravenous patients were comparable by age, body mass index and ASA (American Society of Anesthesiologists) scores. There was a protocol violation, as fewer totally intravenous patients received pre-medication (16/26 vs. 8/27 p < 0.001). Totally intravenous patients had significantly higher consumption of ketobemidon (mean 2.35 vs. 5.43 mg/24 h p < 0.004). Within the totally intravenous group, scores for pain at 24 hours were significantly higher as compared with 4-hour scores (p = 0.012). At 24 hours, scores for nausea were significantly higher for the totally intravenous group (1.87 vs. 3.21 p = 0.014). Length of stay did not differ significantly (mean 649 vs. 729 min p > 0.2). Costs of medication were significantly higher for the totally intravenous group (mean 211 vs 285 NOK p <0.001). The use of totally intravenous anaesthesia led to more nausea and more expenses than mixed anaesthesia in laparoscopic gynaecologic day-care surgery. No recommendations for either method can be made because of the non-randomized design.


Urine scent marking (USM): a novel test for depressive-like behavior and a predictor of stress resiliency in mice.
Decreased interest in pleasurable stimuli including social withdrawal and reduced libido are some of the key symptomatic criteria for major depression, and thus assays that measure social and sexual behavior in rodents may be highly appropriate for modeling depressive states. Here we present a novel approach for validating rodent models of depression by assessing male urine scent marking (USM) made in consequence to a spot of urine from a proestrous female. USM is an ethologically important form of sexual communication expressed by males to attract females. The expression of this behavior is highly sensitive and adaptive to environmental cues and social status. We hypothesized that male USM behavior offers a naturalistic measure of social motivation that can be used to evaluate hedonic behaviors relevant to the study of mood disorders. We demonstrated that 1) adult male mice displayed a strong preference for marking proestrous female urine with a high degree of specificity, 2) exposure to chronic social defeat profoundly decreased USM whereas exposure to environmental enrichment increased USM, 3) the standard antidepressant fluoxetine reversed declines in USM induced by social defeat, 4) USM behavior closely correlated with other hedonic measures, and 5) USM scores in non-stressed mice predicted behavioral outcomes after defeat exposure such that mice displaying high preference for marking female urine prior to social defeat showed behavioral resiliency after social defeat. The findings indicate that the USM test is a sensitive, validated measure of psychosocial stress effects that has high predictive value for examination of stress resiliency and vulnerability and their neurobiological substrates.


Effect of 2% lidocaine continuous epidural infusion for thoracic or lumbar herpes-zoster-related pain.
Few treatments are effective to manage herpes-zoster (HZ)-related pain. This retrospective study focused on the efficacy of 2% lidocaine continuous epidural infusion on pain control and quality of life in patients with thoracic or lumbar HZ.A total of 256 patients with thoracic or lumbar HZ were reviewed for this study. Patients included in the study were divided into continuous epidural infusion (70 mL 2% lidocaine + 180 mL 0.9% normal saline) and medical therapy group (group1) and only medical therapy group (group2). European Organization for Research and Treatment of Cancer and Izbicki pain score were used to evaluate the pain control and quality of life before therapy, and 6 and 9 months after therapy.For 256 patients with HZ (thoracic HZ = 162, lumbar HZ = 94), 53.1% was women. Mean ± standard deviation age was 69.4 ± 9.5 ( range, 38-85) years. Significant differences between the 2 groups in terms of quality of life and pain control were detected after 6 and 9 months follow-up (P < .001). For patients with HZ at 1 to 3 months after rash onset, the pain score was significantly lower in group 1 (P < .001). Sixteen patients with postherpetic neuralgia (PHN) underwent continuous epidural infusion therapy. Only 4 patients achieved satisfactory pain relief. Seven patients required analgesic drugs, and 6 patients still were unable to work, 10/16 (62.5%) patients had readmission. In addition, the pain score was higher in patients with HZ with diabetes (P < .001). Epidural infection occurred in 6 patients (8.8%), catheter dislodgement in 4 patients (5.8%), and catheter leakage in 3 patients (4.4%). There was no spinal epidural abscesses occurred.2% lidocaine continuous epidural infusion therapy can lead to sustained pain relief and improve the quality of life in patients with for thoracic or lumbar HZ at 1 to 3 months after rash onset. Epidural lidocaine is avoided for the treatment PHN, and the level of glucose might be associated with zoster-related pain.


Investigational approaches for mesothelioma.
Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000-2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment - INAHTA), NIH database (USA), International Pleural Mesothelioma Program - WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.


Lysolecithin:lysolecithin acyltransferase from rabbit lung. A conformational study.
The enzyme lysolecithin:lysolecithin acyltransferase from rabbit lung has been found to have a relatively disordered conformation in solutions of high ionic strength. The protein exhibited an ordering of structure when salt was suppressed. This conformational change was concomitant with the loss of transacylase activity, the hydrolytic reaction remaining unchanged. Addition of NaCl caused a progressive disordering of structure with a parallel increase of transacylase activity. The acid denaturation of the protein, at low and high ionic strengths, showed that the ionization of groups with pK in the range 5.9-6.4 was essential for denaturation. The structure was stable at basic pH. The addition of lipids resulted in a non-specific stabilization of the disordered conformation, in the same manner as the addition of NaCl. From these results, it is suggested that there are two conformations for this protein which differ in their ability to bind lysolecithin molecules in the enzyme deacylation step of the reaction. This hypothesis agrees with previously published properties of the enzyme, concerning aggregation with other proteins and kinetic data. From the amino acid composition and conformational properties, the authors suggest that this enzyme could be a peripheral membrane protein.


Premature loss of primary teeth: part I, its overall effect on occlusion and space in the permanent dentition.
Premature loss of primary molars causes, without doubt, permanent changes in regard to space and sagittal molar relations, in the permanent dentition. The changes are due to drifting of teeth and lack of growth, and such changes should, whenever possible, be prevented. In part two of this series of papers, a further analysis of the data will be presented.


Nonlinear Analysis of Auscultation Signals in TCM Using the Combination of Wavelet Packet Transform and Sample Entropy.
Auscultation signals are nonstationary in nature. Wavelet packet transform (WPT) has currently become a very useful tool in analyzing nonstationary signals. Sample entropy (SampEn) has recently been proposed to act as a measurement for quantifying regularity and complexity of time series data. WPT and SampEn were combined in this paper to analyze auscultation signals in traditional Chinese medicine (TCM). SampEns for WPT coefficients were computed to quantify the signals from qi- and yin-deficient, as well as healthy, subjects. The complexity of the signal can be evaluated with this scheme in different time-frequency resolutions. First, the voice signals were decomposed into approximated and detailed WPT coefficients. Then, SampEn values for approximated and detailed coefficients were calculated. Finally, SampEn values with significant differences in the three kinds of samples were chosen as the feature parameters for the support vector machine to identify the three types of auscultation signals. The recognition accuracy rates were higher than 90%.


The role of prokineticins in recurrent implantation failure.
The aim of the present study was to investigate the expression patterns of prokineticins (PROK) and prokineticin receptors (PROKR) in the endometrium of women with recurrent implantation failure (RIF). Fifteen (15) women with RIF and 15 fertile controls were enrolled in this study. Endometrial samples were taken from study participants with an endometrial biopsy cannula during the implantation window. Real time polymerase chain reaction and immunohistochemistry were used to determine PROK/PROKR mRNA expression and protein localization, respectively. PROK1 mRNA levels were 6.09 times higher compared to endometrial samples obtained from women with RIF than in samples obtained from fertile controls, whereas PROKR1 mRNA levels were 2.46 times lower in endometrial samples obtained from women with RIF than in samples from fertile controls. In addition, decreased PROKR1 was supported by immunohistochemistry analysis at protein level. There was no statistically significant difference between women with RIF and fertile controls regarding PROK2 and PROKR2 levels. Altered expression of the PROK1/PROKR1 system could be one of the numerous abnormalities in the endometrium of women with RIF.


Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn Study.
Endothelial dysfunction and low-grade inflammation are key phenomena in the pathobiology of cardiovascular disease (CVD). Their dietary modification might explain the observed reduction in CVD that has been associated with a healthy diet rich in fruit, vegetables and fish, low in dairy products and with moderate alcohol and red wine consumption. We investigated the associations between the above food groups and endothelial dysfunction and low-grade inflammation in a population-based cohort of Dutch elderly individuals. Diet was measured by food frequency questionnaire (n = 801; women = 399; age 68.5 ± 7.2 years). Endothelial dysfunction was determined (1) by combining von Willebrand factor, and soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, endothelial selectin and thrombomodulin, using Z-scores, into a biomarker score and (2) by flow-mediated vasodilation (FMD), and low-grade inflammation by combining C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and sICAM-1 into a biomarker score, with smaller FMD and higher scores representing more dysfunction and inflammation, respectively. We used linear regression analyses to adjust associations for sex, age, energy, glucose metabolism, body mass index, smoking, prior CVD, educational level, physical activity and each of the other food groups. Moderate [β (95% CI) -0.13 (-0.33; 0.07)] and high [-0.22 (-0.45; -0.003)] alcohol consumption, and red wine [-0.16 (-0.30; -0.01)] consumption, but none of the other food groups, were associated with a lower endothelial dysfunction biomarker score and a greater FMD. The associations for FMD were, however, not statistically significant. Only red wine consumption was associated with a lower low-grade inflammation biomarker score [-0.18 (-0.33; -0.04)]. Alcohol and red wine consumption may favourably influence processes involved in atherothrombosis.


Effect of intestinal lymphatic circulation blockage in two-hit rats.
To study the effect of blocking intestinal lymphatic circulation in two-hit rats and explore the significance of intestinal lymphatic circulation in two-hit. Wistar rats were divided equally into three groups: mesenteric lymph duct ligation group, non-ligation group and sham group. Mesenteric lymph was diverted by ligation of mesenteric lymph duct, and the two-hit model was established by hemorrhage and lipopolysaccharide (LPS) methods. All rats were sampled for serum pre-experiment and 24 h post-experiment. The organs including kidney, liver, lung and heart were collected for pathomorphologic observation and biochemical investigation. The nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in serum and tissue homogenate. Pathomorphology study showed that the structures of kidney, lung, liver and heart tissues were normal in sham group; congestion, degeneration and necrosis in non-ligation group; but only mild lesions in ligation group. After two-hits, the contents of AST, ALT, BUN, Cr and LDH-1 in the serum of non-ligation group and ligation group were obviously higher than that in pre-experiment group and sham group, but obviously lower than that in non-ligation group. The contents of NO(2)(-)/NO(3)(-), NOS, iNOS and MDA in the serum of non-ligation group were significantly increased, compared with pre-experiment and sham group, but SOD was significantly lower. These parameters were significantly different in ligation group compared with that in sham group, but NO2-/NO3-, iNOS and MDA in ligation group were significantly lower than that in non-ligation group. Ligation of mesenteric lymph duct could improve the disturbance of organic function and morphologic damage in two-hit rats; the lymphatic mechanism in two-hit should be emphasized.


Chromosomal axis formation and meiotic progression in chicken oocytes: a quantitative analysis.
The assembly and disassembly of the synaptonemal complexes (SCs) correlate with the progression of meiotic prophase I. Using immunostaining of the cohesin component SMC3, which is present in the axial elements of the SC, we characterized the synaptic process in chicken oocytes and quantified the frequency of the different prophase stages at hatching and at 3 different ages after hatching. The analysis provides detailed quantitative data regarding the meiotic stages in the chicken ovary showing that the maximum amount of pachytene oocytes is found around hatching and that oocytes reach the diplotene stage 5 days after entering into meiosis. We confirmed the asynchrony of the meiotic development in the female chicken gonad showing that the ovary has a composite population of cells at different stages from day 17 before hatching and for several days after hatching. The significance of these results is discussed in relationship to functional experimental procedures that involve avian oocytes.


Crystallization of GreA, a transcript cleavage factor from Escherichia coli.
GreA is a 17.6 kDa protein from Escherichia coli that induces cleavage of the nascent transcript in the elongating complex of RNA polymerase, followed by release of the 3'-terminal fragment. Crystals of GreA have been obtained from polyethylene glycol 4000, 2-propanol and sodium citrate, pH 5.6 and have been propagated by a novel seeding procedure. The crystals diffract beyond 2 A resolution and belong to the orthorhombic space group P2(1)2(1)2(1), with cell dimensions a = 101.7 A, b = 42.22 A, c = 40.05 A and with one molecule in the asymmetric unit.


Chloramphenicol: screening and review to evaluate its potential beneficial effects in leukaemia.
Chloramphenicol is an antimicrobial agent having a very broad-spectrum of activity including Gram-positive bacteria, Gram-negative bacteria and anaerobes. However the use of chloramphenicol has reduced over a period of time due to the adverse effects of causing bone marrow depression or in some cases severe aplastic anaemia. As the effects are seen on the bone marrow cell, it was intended to find out if these adverse effects could be used for the benefits in leukaemia patients, using in-vitro study on leukaemic cell lines. The study showed inhibition of growth of the leukaemia cells by chloramphenicol which was comparable to or better than daunorubicin in some cell lines. The article also discusses the other adverse effect profile of chloramphenicol compared with anticancer drugs and its potential benefit in leukaemia and in neutropenic fever.


Nasopharyngeal pertussis toxin IgA antibodies in the diagnosis of pertussis in Australian community patients.
Nasopharyngeal aspirate (NPA) Bordetella pertussis-specific IgA antibody assay using whole-cell (WC) antigen has previously been shown to have promise in the diagnosis of patients with suspected pertussis. Recently, the use of WC assays in serum have been replaced by pertussis toxin (PT) because of specificity concerns. In this study, PT and WC B. pertussis-specific IgA antibody was assayed in 491 NPAs. Specimens also had molecular testing for the presence of B. pertussis and B. parapertussis as per the usual laboratory protocol. Positive concordance of the two serological assays was 51.2%, negative concordance was 67.5% and total concordance was 75.8%. 99 of 119 discordant specimens were resolved by utilising the B. pertussis polymerase chain reaction (PCR) result and clinical status, and yielded a sensitivity of 57.6% and a specificity 97.7% for WC, with 90.2% and 93.1%, respectively, for the PT assay (p < 0.00025 and 0.025-0.01). In contrast, the sensitivity of PCR was only 19.1% in this cohort. We conclude that specificity is not a significant issue for mucosal pertussis-specific IgA assays using WC, but the superior sensitivity of the PT assay favours the latter method. This assay, combined with PCR assays, should significantly improve the diagnosis of pertussis cases.


Grandparents' Experience of Autism Spectrum Disorder: Identifying Primary Themes and Needs.
Limited information is available regarding the first person perspective of grandparents of children with Autism Spectrum Disorders (ASD). In the present study, 1870 grandparents of a child with ASD participated in a nationwide, online, anonymous, 30-minute survey and responded to open-ended questions including their "greatest challenges and greatest joys" as the grandparent of a child on the autism spectrum. A grounded theory approach to qualitative analysis revealed four overarching categories: a Desire for Connection, Barriers to Care, Celebration of Progress, and Personal Reactions. Despite the presence of significant challenges grandparents often experienced positivity in their role, and engaged in radical acceptance of their grandchild as well as transformative insight and advocacy. Specific recommendations are offered to help address grandparents' needs and capitalize upon their resilience.


Early risk stratification using clinical findings in patients with acute myocardial infarction.
The value of non-invasive, clinical variables in predicting short-term outcome after acute myocardial infarction has been prospectively studied using multivariate analysis in a learning population of 1724 patients and a validation sample of 588 cases. Early risk stratification of CCU mortality could be made with 89.4% accuracy by using 7 simple clinical variables (Killip class, systolic blood pressure, heart rate, age, intraventricular conduction disturbance, localization of infarction and obesity index) recorded on admission. A discriminant function formula could also be constructed resulting in a maximal classification of 89.3% and predictive values of 91.8% and 77.9%, respectively, for 28-day survival and early death prediction in the learning population. Accuracy figures dropped only slightly (1 to 5%) in the independent test set. Predictions could be made with a high degree of accuracy, especially in the upper and lower ranges of the discriminant risk score. This investigation demonstrates that a fairly good estimation of prognosis can be made by means of discriminant analysis of clinical findings gathered routinely in most CCU's.


Logistic model of glucose-regulated C-peptide secretion: hysteresis pathway disruption in impaired fasting glycemia.
The present analysis tests the hypothesis that quantifiable disruption of the glucose-stimulated insulin-secretion dose-response pathway mediates impaired fasting glycemia (IFG) and type 2 diabetes mellitus (DM). To this end, adults with normal and impaired fasting glycemia (NFG, n = 30), IFG (n = 32), and DM (n = 14) were given a mixed meal containing 75 g glucose. C-peptide and glucose were measured over 4 h, 13 times in NFG and IFG and 16 times in DM (age range 50-57 yr, body mass index 28-32 kg/m(2)). Wavelet-based deconvolution analysis was used to estimate time-varying C-peptide secretion rates. Logistic dose-response functions were constructed analytically of the sensitivity, potency, and efficacy (in the pharmacological sense of slope, one-half maximal stimulation, and maximal effect) of glucose's stimulation of prehepatic insulin (C-peptide) secretion. A hysteresis changepoint time, demarcating unequal glucose potencies for onset and recovery pathways, was estimated simultaneously. According to this methodology, NFG subjects exhibited distinct onset and recovery potencies of glucose in stimulating C-peptide secretion (6.5 and 8.5 mM), thereby defining in vivo hysteresis (potency shift -2.0 mM). IFG patients manifested reduced glucose onset potency (8.6 mM), and diminished C-peptide hysteretic shift (-0.80 mM). DM patients had markedly decreased glucose potency (18.8 mM), reversal of C-peptide's hysteretic shift (+4.5 mM), and 30% lower C-peptide sensitivity to glucose stimulation. From these data, we conclude that a dynamic dose-response model of glucose-dependent control of C-peptide secretion can identify disruption of in vivo hysteresis in patients with IFG and DM. Pathway-defined analytic models of this kind may aid in the search for prediabetes biomarkers.


Ulcerated and nonulcerated nontuberculous cutaneous mycobacterial granulomas in cats and dogs.
Mycobacterial granulomas of the skin and subcutis can be caused by one of a number of pathogens. This review concentrates on noncultivable species that cause diseases characterized by focal granuloma(s), namely leproid granuloma (in dogs) and feline leprosy (in cats). Clinically indistinguishable lesions can be caused by tuberculous organisms (Mycobacterium bovis and Mycobacterium microti) and members of the Mycobacterium avium complex. Rapidly growing mycobacterial species that cause infection of the subcutaneous panniculus associated with draining tracts are not discussed. Disease caused by Mycobacterium ulcerans is an important emerging differential diagnosis for ulcerated cutaneous nodules in certain localized regions. CLINICAL LESIONS: Lesions comprise one or multiple nodules in the skin/subcutis. These are generally firm and well circumscribed, and typically become denuded of hair. They may or may not ulcerate, depending on the virulence of the causal organisms and the immune response of the host. The most inexpensive, noninvasive means of diagnosis is by submission of methanol-fixed, Romanowsky-stained smears to a Mycobacterium Reference Laboratory after detecting negatively stained or acid-fast bacilli on cytological smears. Scrapings of material from slides usually provide sufficient mycobacterial DNA to enable identification of the causal organism using sequence analysis of amplicons after PCR using specific mycobacterial primers. Therapy relies upon a combination of marginal resection of easily accessible lesions and treatment using two or three drugs effective against slowly growing mycobacteria, choosing amongst rifampicin, clarithromycin, clofazimine and pradofloxacin/moxifloxacin.


[Growth inhibition and apoptosis-inducing effects of phytic acid in human gastric carcinoma cells].
To explore the growth inhibition and apoptosis-inducing effects of phytic acid in human gastric cancer SGC-7901 cells. The growth inhibition action of phytic acid on SGC-7901 cells was examined by MTT assay. AO/EB fluorescence staining and DNA ladder assay were applied to study the proapoptosis effects of phytic acid. The expression of apoptosis relative proteins, P53, were analyzed by using immune histochemisty method. Phytic acid treatment significantly inhibited the growth of human gastric cancer cell SGC-7901 and markedly caused their apoptosis following downregulation of P53 protein expression. The downregulation of apoptosis relative protein P53 expression was the possible mechanism of phytic acid induced growth inhibition and apoptosis in SGC-7901 cells.


Influence of gamma-rays on the mouse liver cytochrome P450 system and its modulation by phenothiazine drugs.
Phenothiazine drugs have been found to sensitize hypoxic cancer cells while offering protection to normal cells. Since phenothiazines are known to induce the cytochrome P450 system, its radiomodulation by phenothiazines has been examined. Mice were administered phenothiazines intraperitoneally and irradiated with different doses of gamma-rays at 1.38 Gy/min. The activities of NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase, the content of cytochrome P450 and b5, the extent of lipid peroxidation as well as the activities of LDH, XO, SOD, GST and DTD were determined in the liver. The levels of different components of the cytochrome P450 system and antioxidant enzymes were enhanced up to 5 Gy and decreased thereafter. However, a progressive increase was noticed in peroxidative damage and the activities of LDH and XO. Administration of phenothiazines enhanced the radiation effect on components of the cytochrome P450 system (except NADH-cytochrome b5 reductase) and the activities of SOD, GST and DTD. Concomitantly, phenothiazines inhibited lipid peroxidation, LDH and XO. Activation of the cytochrome P450 system by phenothiazines leading to the enhancement of antioxidant potential of animals and free-radical scavenging are attributes of the radioprotective action of phenothiazines.


Triple-negative breast cancer: treatment challenges and solutions.
Triple-negative breast cancers (TNBCs) are defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy (CT). The heterogeneity of the disease has limited the successful development of targeted therapy in unselected patient populations. Currently, there are no approved targeted therapies for TNBC. However, intense research is ongoing to identify specific targets and develop additional and better systemic treatment options. Standard adjuvant and neoadjuvant regimens include anthracyclines, cyclophosphamide, and taxanes. Platinum-based CT has been proposed as another CT option of interest in TNBC. We review the role of this therapy in general, and particularly in patients carrying BRCA germ-line mutations. Available data concerning the role of platinum-based CT in TNBC were acquired primarily in the neoadjuvant setting. The routine use of platinum-based CT is not yet recommended by available guidelines. Many studies have reported the molecular characterization of TNBCs. Several actionable targets have been identified. Novel therapeutic strategies are currently being tested in clinical trials based on promising results observed in preclinical studies. These targets include androgen receptor, EGFR, PARP, FGFR, and the angiogenic pathway. We review the recent data on experimental drugs in this field. We also discuss the recent data concerning immunologic checkpoint inhibitors.


More than one DNA sequence encodes the 2''-O-adenylyltransferase phenotype.
Biochemical and phenotypic assays indicate that three enterobacterial R plasmids isolated in a single hospital encode 2''-O-adenylyltransferase [ANT(2'')], and an ANT(2'')-specific probe was developed from one plasmid. Southern hybridization revealed the three plasmids to be unrelated and, further, showed their ANT(2'')-encoding genes to be different.


In search of mediators of leadership behavior to Team Creativity in Team Start-ups.
Creativity is believed as the first step to innovation, especially in a team or workgroup in an organization. Team Creativity will lead to several innovations in a team, such as product and process innovation. Team leaders play a significant role in embracing Team Creativity. Our study investigates the mediator variables to foster the impact of leadership behavior on Team Creativity in Team Start-up. Earlier research shows that two value-based leadership styles, Transformational and Servant Leadership, significantly affect a team's creativity. We proposed two mediators of leadership behavior to foster Team Creativity: Team Climate and Team Ambidexterity. The sample is early Team Start-ups in several cities in Indonesia, run and led by young people. It is empirical cross-sectional quantitative research with more than 434 participants aggregated into 145 teams. The result shows that Team Climate and Team Ambidexterity are good mediators of Servant and Transformational Leadership behavior to Team Creativity in Team Start-ups. The two variables maximize the impact of leadership behavior on Team Creativity.


Compounding as Abstract Operation in Semantic Space: Investigating relational effects through a large-scale, data-driven computational model.
In many languages, compounding is a fundamental process for the generation of novel words. When this process is productive (as, e.g., in English), native speakers can juxtapose two words to create novel compounds that can be readily understood by other speakers. The present paper proposes a large-scale, data-driven computational system for compound semantic processing based on distributional semantics, the CAOSS model (Compounding as Abstract Operation in Semantic Space). In CAOSS, word meanings are represented as vectors encoding their lexical co-occurrences in a reference corpus. Given two constituent words, their composed representation (the compound) is computed by using matrices representing the abstract properties of constituent roles (modifier vs. head). The matrices are also induced through examples of language usage. The model is then validated against behavioral results concerning the processing of novel compounds, and in particular relational effects on response latencies. The effects of relational priming and relational dominance are considered. CAOSS predictions are shown to pattern with previous results, in terms of both the impact of relational information and the dissociations related to the different constituent roles. The simulations indicate that relational information is implicitly reflected in language usage, suggesting that human speakers can learn these aspects from language experience and automatically apply them to the processing of new word combinations. The present model is flexible enough to emulate this procedure, suggesting that relational effects might emerge as a by-product of nuanced operations across distributional patterns.


Reconstruction of laser beam wavefronts based on mode analysis.
We present the reconstruction of a laser beam wavefront from its mode spectrum and investigate in detail the impact of distinct aberrations on the mode composition. The measurement principle is presented on a Gaussian beam that is intentionally distorted by displaying defined aberrations on a spatial light modulator. The comparison of reconstructed and programmed wavefront aberrations yields excellent agreement, proving the high measurement fidelity.


A dual mode pulsed electro-magnetic cell stimulator produces acceleration of myogenic differentiation.
This paper presents the design and test of a dual-mode electric and magnetic biological stimulator (EM-Stim). The stimulator generates pulsing electric and magnetic fields at programmable rates and intensities. While electric and magnetic stimulators have been reported before, this is the first device that combines both modalities. The ability of the dual stimulation to target bone and muscle tissue simultaneously has the potential to improve the therapeutic treatment of osteoporosis and sarcopenia. The device is fully programmable, portable and easy to use, and can run from a battery or a power supply. The device can generate magnetic fields of up to 1.6 mT and output voltages of +/- 40 V. The EM-Stim accelerated myogenic differentiation of myoblasts into myotubes as evidenced by morphometric, gene expression, and protein content analyses. Currently, there are many patents concerned with the application of single electrical or magnetic stimulation, but none that combine both simultaneously. However, we applied for and obtained a provisional patent for new device to fully explore its therapeutic potential in pre-clinical models.


Breathing adapted radiotherapy for breast cancer: comparison of free breathing gating with the breath-hold technique.
Adjuvant radiotherapy after breast-conserving surgery for breast cancer implies a risk of late cardiac and pulmonary toxicity. This is the first study to evaluate cardiopulmonary dose sparing of breathing adapted radiotherapy (BART) using free breathing gating, and to compare this respiratory technique with voluntary breath-hold. 17 patients were CT-scanned during non-coached breathing manoeuvre including free breathing (FB), end-inspiration gating (IG), end-expiration gating (EG), deep inspiration breath-hold (DIBH) and end-expiration breath-hold (EBH). The Varian Real-time Position Management system (RPM) was used to monitor respiratory movement and to gate the scanner. For each breathing phase, a population based internal margin (IM) was estimated based on average chest wall excursion, and incorporated into an individually optimised three-field mono-isocentric wide tangential photon field treatment plan for each scan. The target included the remaining breast, internal mammary nodes and periclavicular nodes. The mean anteroposterior chest wall excursion during FB was 2.5mm. For IG and EG, the mean excursions within gating windows were 1.1 and 0.7 mm, respectively, whereas for DIBH and EBH the excursions were 4.1 and 2.6mm, respectively. For patients with left-sided cancer, the median heart volume receiving more than 50% of the prescription dose was reduced from 19.2% for FB to 2.8% for IG and 1.9% for DIBH, and the median left anterior descending (LAD) coronary artery volume was reduced from 88.9% to 22.4% for IG and 3.6% for DIBH. Simultaneously, the median ipsilateral relative lung volume irradiated to >50% of the prescribed target dose for both right- and left-sided cancers was reduced from 45.6% for FB to 29.5% for IG and 27.7% for DIBH. For EBH and EG, both the irradiated heart, LAD and lung volumes increased compared to FB. This is the first study to demonstrate the dosimetric benefits of free breathing gated breast cancer radiotherapy. IG compared favourably with DIBH, substantially reducing cardiac doses simultaneous with significant pulmonary tissue sparing.


Medicine and paradigms of embodiment.
This paper suggests that the paradigm of the lived-body developed by Straus , Merleau - Ponty and others has important implications for medical practice and theory. Certain recognized flaws in modern medicine, such as its reductionist tendencies and lack of emphasis on preventive measures are shown to be related to the exclusive use of a Cartesian notion of embodiment . Increased attention to the paradigm of the lived-body emphasizing its unity, purposiveness and " enworldment " could help to beneficially reorient practice. Moreover, this portrayal of the body as an intentional entity may provide a better tool than the traditional view for conceptualizing the psychological and psychosocial components of disease etiology, as well as some newly developed modes of treatment.


Gas chromatographic determination of ametryn and its metabolites in tropical root crops.
Residue analysis of the herbicide ametryn (2-methylthio-4-ethylamino-6-isopropylamino-s-triazine) is widely known but an analytical method for determining its metabolites has not yet been reported in the literature. A method has been developed for the extraction and determination of ametryn and 3 metabolites, 2-methylthio-4-amino-6-isopropylamino-s-triazine (GS-11354), 2-methylthio-4,6-diamino-s-triazine (GS-26831), and 2-methylthio-4-amino-6-ethylamino-s-triazine (GS-11355) in taniers , yams , cassava. Residues were extracted from crops with ethyl acetate-toluene (3 + 1 v/v), using a Polytron homogenizer and anhydrous sodium sulfate added for drying. The extracts were cleaned up by automated gel permeation chromatography on Bio-Beads SX-3 gel in the same solvent system. Quantitative determination was performed by gas chromatographic (GC) analysis on a column packed with 5% DEGS -PS on 100-120 mesh Supelcoport using either an N-P detector or a flame photometric detector ( FPD ) in the sulfur mode. Minimum detection by the flame photometric detector is 10 ng each for ametryn , GS-11354, and GS-11355 and 21 ng for GS-26831; by the N-P detector, 0.3 ng of each component gives easily quantitatable peaks. On a parts per million basis, starting with 25 g sample, the FPD detected a minimum level of 0.04 microgram/g each for ametryn , GS-11354, and GS-11355, and 0.08 microgram/g for GS-26831. The N-P detector could detect 0.0024 microgram/g for all 4 compounds. In addition to superior sensitivity, instrumental conditions allowed the complete separation of components in 10 min, for the N-P detector; more than 30 min was required for the FPD . Recoveries from fortified crops ranged from 67 to 111% at levels of 0.1-1.0 microgram/g.


Influence of clearcoats on the spectral and physical properties of electrochemically formed colored passive layers on zirconium.
We report on the application and characterization of two commercial polymer clearcoats to electrochemically formed colored passive layers on zirconium with the aim of providing effective physical and chemical protection while allowing the unique and colorful appearance of the colored passive layers to show through. Thin layers of an acrylic automotive clearcoat ( approximately 3.5 mum thick) and an epoxy marine clearcoat ( approximately 8.5 mum thick) were applied to the colored zirconium surfaces via spin coating and were found to only slightly modify their visual properties, maintaining their vibrant colors. As clearcoats were applied, the outer surface was found to be smoother than the surface of colored zirconium, thereby reducing potential wear from friction and the adhesion of fine dirt. Clearcoat-protected samples were found to wet less easily than colored zirconium alone, thus furthering its protection against damage in ambient (surface weathering) and aqueous media (aqueous corrosion). Light microscopy experiments at a 50-400x magnification revealed the absence of any structural defects in the clearcoats. The clearcoats show the ability to protect colored zirconium from physical and chemical damage, with the automotive clearcoat exhibiting superior adhesion. Our electrochemical coloring combined with the application of clearcoats creates a novel system that possesses unique esthetic properties while simultaneously offering protection against various forms of environmental damage such as weathering or corrosion.


A Multiscale Approach to the Smart Deployment of Micro-Sensors over Lightweight Structures.
A topology optimization approach has been recently proposed to maximize the sensitivity to damage of measurements, collected through a network of sensors to be deployed over thin plates for structural health monitoring purposes. Within such a frame, damage is meant as a change in the structural health characterized by a reduction of relevant stiffness and load-carrying properties. The sensitivity to a damage of unknown amplitude and location is computed by comparing the response to the external actions of the healthy structure and of a set of auxiliary damaged structures, each one featuring reduced mechanical properties in a small region only. The topology optimization scheme has been devised to properly account for the information coming from all of the sensors to be placed on the structure and for damage depending on its location. In this work, we extend the approach within a multiscale frame to account for three different length scales: a macroscopic one, linked to the dimensions of the whole structure to be monitored; a mesoscopic one, linked to the characteristic size of the damaged region; a microscopic one, linked to the size of inertial microelectromechanical systems (MEMS) to be used within a marginally-invasive health monitoring system. Results are provided for a square plate and for a section of fuselage with stiffeners, to show how the micro-sensors have to be deployed to maximize the capability to detect a damage, to assess the sensitivity of the results to the measurement noise and to also discuss the speedup in designing the network topology against a standard single-scale approach.


Analyzing the experiences of adolescent control rats: Effects of the absence of physical or social stimulation on anxiety-like behaviour are dependent on the test.
The present study was designed to systematically assess the control experience routinely used in our laboratory as part of studies on predator odour stress. Specifically, we examined effects of the physical and social components of this control experience on measures of anxiety-like behaviour in adolescent rats. Adolescent animals are at increased susceptibility to environmental perturbations and have been used for such studies much less often. Long-Evans rats of both sexes were subjected to physical stimulation (Exposed or Unexposed) and social stimulation (Single-Housed or Pair-Housed), resulting in four groups. Exposed rats received six 30-min exposures to an enclosed arena containing an unscented piece of cat collar occurring between adolescence and early adulthood, while Unexposed remained in the home cage. Groups of Exposed and Unexposed animals were housed singly (Single-Housed) from early adolescence to early adulthood or Pair-Housed during this time. Experimental procedures began in adolescence and involved repeated assessment of startle amplitude (measure of anxiety-like behaviour) and prepulse inhibition (PPI; a measure of sensorimotor gating) to gauge the short-term impact of social and/or physical stimulation. All animals were re-paired in adulthood prior to a final startle/PPI session to assess if isolation limited to adolescence could impose long-term effects that were not reversible. We also measured anxiety-like behaviour in adulthood using an extended open field test (EOFT; addition of novel objects to the open field on later days), and the elevated plus maze task (EPM), as well as a sucrose preference test (SPT) to measure anhedonia. An absence of social or physical stimulation resulted in increased startle amplitude and some measures of anxiety-like behaviour in the EOFT, but a reduction in such anxiety-like behaviour in the EPM task. These results suggest common neural substrates for the physical and social experiences. Performance in the SPT was unaltered by any experimental treatments. Sensorimotor gating, as measured by PPI, was increased in the absence of physical stimulation with no short-term effect of isolation, or of re-pairing. These results indicate the importance of considering individual components of the rearing environment of rats, while showing the need to use multiple assays of anxiety-like behaviour.


Molecular interactions between the olive and the fruit fly Bactrocera oleae.
The fruit fly Bactrocera oleae is the primary biotic stressor of cultivated olives, causing direct and indirect damages that significantly reduce both the yield and the quality of olive oil. To study the olive-B. oleae interaction, we conducted transcriptomic and proteomic investigations of the molecular response of the drupe. The identifications of genes and proteins involved in the fruit response were performed using a Suppression Subtractive Hybridisation technique and a combined bi-dimensional electrophoresis/nanoLC-ESI-LIT-MS/MS approach, respectively. We identified 196 ESTs and 26 protein spots as differentially expressed in olives with larval feeding tunnels. A bioinformatic analysis of the identified non-redundant EST and protein collection indicated that different molecular processes were affected, such as stress response, phytohormone signalling, transcriptional control and primary metabolism, and that a considerable proportion of the ESTs could not be classified. The altered expression of 20 transcripts was also analysed by real-time PCR, and the most striking differences were further confirmed in the fruit of a different olive variety. We also cloned the full-length coding sequences of two genes, Oe-chitinase I and Oe-PR27, and showed that these are wound-inducible genes and activated by B. oleae punctures. This study represents the first report that reveals the molecular players and signalling pathways involved in the interaction between the olive fruit and its most damaging biotic stressor. Drupe response is complex, involving genes and proteins involved in photosynthesis as well as in the production of ROS, the activation of different stress response pathways and the production of compounds involved in direct defence against phytophagous larvae. Among the latter, trypsin inhibitors should play a major role in drupe resistance reaction.


Safety threshold of intravitreal clonidine in rabbit's eyes.
To determine the safe dose of intravitreal clonidine (IVC), a potential drug for neuroprotection and angiogenesis inhibition in rabbits. A total of 28 rabbits were divided into four groups. Three groups received IVC with concentrations of 15 (Group A), 25 (Group B), and 50 (Group C) µg/0.1 mL and the control group (Group D) received 0.1 mL balanced salt solution (BSS). To investigate IVC safety, electroretinography (ERG) was performed at baseline, then at 1, 4 and 8wk after injection. After last ERG, all rabbits were euthanized, their eyes were enucleated and subjected to routine histopathological evaluation, immunohistochemistry for glial fibrillary acidic protein (GFAP) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Based on ERG, histopathology, GFAP and TUNEL assay findings, 15 µg IVC was determined as the safe dose in rabbit eyes. While, the results of routine histopathology and TUNEL assay were unremarkable in all groups, toxic effects attributed to 25 and 50 µg IVC were demonstrated by ERG and GFAP tests. Totally 15 µg clonidine is determined as the safe dose for intravitreal injection in rabbits. Contribution of IVC in neuroprotection and inhibition of angiogenesis deserve more studies.


A genetic origin for acid-base imbalance triggers the mitochondrial damage that explains the autoimmune response and drives to gastric neuroendocrine tumours.
Type I gastric neuroendocrine tumors (gNETs) arise from hypergastrinemia in patients with autoimmune chronic atrophic gastritis. According to the classical model, the gastric H+/K+ ATPase was the causative autoantigen recognized by CD4+ T cells in chronic autoimmune scenario that secretes IL-17 and correlates with parietal cell (PC) atrophy, which drives to gastric achlorhydria and increases the risk for gastric neoplasms. However, the mechanism by which the inflammatory response correlates with PC atrophy is not clearly defined. Recently, we found that the ATP4Ap.R703C mutation impaired PC function and gastric acidification, which drove familial gNET. Our group constructed a knock-in mouse model for the ATP4A mutation, which has served us to better understand the relation between impaired capability to export protons across the plasma membrane of PCs and tumor progression. The ATP4Ap.R703C mutation drives gastric achlorhydria, but also deregulates the acid-base balance within PCs, affecting mitochondrial biogenesis. Mitochondrial malfunction activates ROS signaling, which triggers caspase-3-mediated apoptosis of parietal cells. In addition, when gastric euchlorhydria was restored, mitochondrial function is recovered. Infection by H. pylori promotes destabilization of the mitochondria of the PCs by a mechanism similar to that described for APT4Ap.R703C carriers. A genetic origin that drives mitochondria alteration would initiate the gastric chronic inflammation instead of the classical IL-17 secretion-mediated mechanism explanation. Gastric euchlorhydria restoration is suggested to be indicated for mitochondrial recover. Our results open a new window to understand gastric neoplasms formation but also the inflammatory mechanisms and autoimmune disorders conducted by genetic origin that composes a premalignant scenario.


Impact of Group Management and Transfer on Individual Sociality in Highland Cattle (Bos taurus).
The sociality of cattle facilitates the maintenance of herd cohesion and synchronization, making these species the ideal choice for domestication as livestock for humans. However, livestock populations are not self-regulated, and farmers transfer individuals across different groups. Individuals consequently have to adapt to different group compositions during their lives rather than choose their own herd mates, as they would do in the wild. These changes may lead to social instability and stress, entailing potentially negative effects on animal welfare. In this study, we assess how the transfer of Highland cattle (Bos taurus) impacts individual and group social network measures. Four groups with nine different compositions and 18 individual transfers were studied to evaluate 1) the effect of group composition on individual social centralities and 2) the effect of group composition changes on these centralities. This study reveals that the relative stability of dyadic spatial relationships between changes in group composition or enclosure is due to the identities of transferred individuals more than the quantity of individuals that are transferred. Older cattle had higher network centralities than other individuals. The centrality of individuals was also affected by their sex and the number of familiar individuals in the group. This study reveals the necessity of understanding the social structure of a group to predict social instability following the transfer of individuals between groups. The developing of guidelines for the modification of group composition could improve livestock management and reduce stress for the animals concerned.


Long-term outcome of adding mycophenolate mofetil to tacrolimus for nephrotoxicity following liver transplantation.
Mycophenolate mofetil (MMF) has no known nephrotoxicity. This report examines the outcome in patients who received MMF for renal impairment on tacrolimus-based immunosuppression. From 1995 to 1996, twelve liver transplantation (LTx) patients (mean age 54.6 years) with serum creatinine >1.8 mg/dl were included in the study. MMF was introduced and tacrolimus dose was reduced by 30-50%. Each patient was followed for 6 years. Renal function showed improvement in seven patients, deterioration in four, and no change in one patient. Overall mean serum creatinine decreased from 2.5 to 1.9 mg/dl at 6 months but increased to 2.2 mg/dl at 18 to 24 months. After that, renal function remained stable for 72 months. Iothalamate clearance showed 18.5% improvement at 1 year. Three patients developed renal failure. Six patients died in the follow-up period. Addition of MMF with reduced tacrolimus dose resulted in sustained improvement in renal function in 58% of patients.


Motivating staff: a look at assumptions.
Motivational theory can be a helpful tool to enrich staff's jobs. Some of the literature seems to promise that if we master certain formulas or learn certain procedures we can motivate employees to incredible levels of performance. This discussion lays to rest such expectations. Reviewing the concept of work motivation and pointing out the useful elements that are at the heart of the various motivational theories, the author seeks to make sense of the diversity and seeming contradictions among the theories. The discussion is directed specifically to nursing home administrators; however, the author's perspective can be used by all nursing administrators to integrate theory with the real world situation to provide a motivating environment for staff.


Identification of two fungal endophytes associated with the endangered orchid Orchis militaris L.
A survey of the endangered orchid Orchis militaris populations was carried out in north-eastern Italy. The occurrence of fungal root endophytes was investigated by light and electron microscopies and molecular techniques. Two main sites of presence were individuated in the Euganean Hills, differing as to the percentage of flowering individuals and of capsules completing maturity. Fluorescence microscopy revealed an intracellular cortical colonization by hyphal pelotons. Two ITS PCR products co-amplified. Sequencing revealed for the former an identity and a high similarity (99%) with a Tulasnellaceae (Basidiomycota) fungus found within tissues of the same host in independent studies in Hungary and Estonia, suggesting an interesting case of tight specificity throughout the Eurosiberian home range. The second amplicon had 99% similarity with Tetracladium species (Ascomycota) recently demonstrated as potential endophytes. TEM revealed two different hyphal structures. Double fungal colonization appears to occur in Orchis militaris and the possible requirement of a specific fungal partner throws light on the causes of this plant's rarity and threatened status.