Isolation of protein kinase C-alpha-regulated cDNAs associated with breast tumor aggressiveness by differential mRNA display.
Elevated levels of protein kinase C (PKC) are associated with increased metastatic capacity in both human breast cancer cells and breast tumors. MCF-7 breast cancer cells stably transfected with PKC-alpha were recently shown to display a more aggressive phenotype and increased tumorigenicity in nude mice. To identify genes involved in the progression to the aggressive phenotype, mRNA differential display was performed to isolate cDNAs that are differentially expressed between the parental, non-metastatic MCF-7 cell line and the metastatic derivative MCF-7-PKC-alpha cell line. One cDNA was identified which was upregulated and four cDNAs were downregulated in MCF-7-PKC-alpha cells. The upregulated cDNA may be a differentiation-specific gene as it is 100% homologous to a putative glialblastoma cell differentiation-related protein, GBDR1. DNA sequence analysis and flow cytometry revealed that three of the downregulated cDNAs correspond to histone 3.B, and integrins alpha3 and alpha6. The fourth downregulated cDNA clone, G2Q, is a novel sequence. G2Q is expressed in normal breast and bronchial tissue, but is downregulated in a variety of tumor cell lines and in aggressive primary and secondary breast tumors, suggesting that G2Q may be a useful prognostic indicator of tumor aggressiveness. Further, downregulation of G2Q expression in the non-metastatic MCF-7 cells by antisense oligonucleotides resulted in increased in vitro invasive capacity of these cells in a Matrigel matrice. This study provides the basis for identifying new genes involved in breast tumor progression and the role that PKC plays in the pathogenesis of this cancer.


Evidence that brain aromatization regulates LH secretion in the male dog.
A variety of data suggest an independent role for androgens and estrogens in the regulation of luteinizing hormone (LH) secretion in the male. Estrogens, in the male are primarily derived from testicular androgens that are aromatized both in peripheral tissues and in the CNS. Our prior data suggested a pharmacologic regimen that blocked CNS aromatization without lowering peripheral estrogen or testosterone levels. Such experimental conditions would permit assessment of the relative roles of CNS versus peripheral aromatization in the regulation of LH secretion. We utilized this regimen (aminoglutethimide, a potent aromatase inhibitor, and hydrocortisone) in seven adult male dogs for 14 days. Plasma LH rose to castrate levels, 450% above control values on days 7 and 14. These LH increments stimulated similar rises in androstenedione, testosterone, and dihydrotestosterone. In contrast, plasma estrone and estradiol concentrations remained constant. The induction of castrate LH levels without a concomitant fall in peripheral androgens or estrogens is best explained by a block of central aromatization and thus a reduction in local hypothalamic concentrations. We conclude that aromatization in the CNS rather than peripheral tissues is the more important site with respect to LH negative feedback in the male dog.


Flibanserin.
To review pivotal clinical trials, pharmacology, contraindications, precautions, and key patient education points of flibanserin for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. A literature search of PubMed using the key words flibanserin and HSDD was conducted in September 2015. There was no time frame to exclude relevant clinical trials. All trials referenced were published between March 2012 and June 2014. Other relevant information was obtained from the Food and Drug Administration (FDA) Web site, press releases, prescribing information from the manufacturer, and ClinicalTrials.gov . All articles in the English language and involving human subjects were reviewed. There are three 24-week, multicenter, randomized, double-blind, placebo-controlled trials that evaluated the efficacy of flibanserin in North American premenopausal women with HSDD. There was 1 trial that studied the effects of flibanserin in postmenopausal women. In all of the trials, the investigators found statistical significant improvements in Female Sexual Function Index (FSFI) desire domain score and satisfying sexual events (SSEs). The most frequently reported adverse events in all flibanserin arms of treatment were somnolence, dizziness, and nausea. Flibanserin, a novel, nonhormonal agent that modulates excitatory and inhibitory neurotransmitters was studied in premenopausal women and has shown efficacy in improving sexual desire and SSEs.


A comparative review of cutaneous pH.
This review describes the role of pH in cutaneous structure and function. We first describe the molecules that contribute to the acidity or alkalinity of the skin. Next, differences in cutaneous pH among species, among individuals of the same species and within individuals are described. The potential functions of cutaneous pH in normal and diseased skin are analysed. For example, cutaneous pH has a role in the selection and maintenance of the normal cutaneous microbiota. In addition, cutaneous acidity may protect the skin against infection by microbes. Finally, there is evidence that a cutaneous pH gradient activates pH-dependent enzymes involved in the process of keratinization.


[Identification of cyanobacteria from genus Anabaena isolated from the rhizosphere of cotton-plant].
Identification of nucleotide sequence of the gene 16S rRNA of cyanobacteria Anabaena variabilis str.21 (Uzb1) exhibits that the strain from root sphere of cotton plants is 99% homologous to a known strain of Anabaena variabilis (EF488831.1). This data confirms the phylogenetic relationship of the strain of cyanobacteria A. variabilis Uzb1 to other described representatives of genus Anabaena as addition to morphological characteristics (presence of akinets (spores) and heterocysts).


Interleukin-17A Inhibitor Secukinumab Treatment in HIV-Positive Psoriasis Patient: A Case Report.
Psoriasis is an immune-mediated chronic inflammatory dermatosis influenced by hereditary and environmental factors. Human immunodeficiency virus (HIV) infection affects the immune system and exacerbates psoriatic lesions. We report the case of a 33-year-old male patient diagnosed with psoriasis vulgaris, psoriatic arthritis and HIV infection. Acitretin capsules, etanercept and high-active antiretroviral therapy (HAART) were effective. Two months after etanercept was discontinued, his condition worsened. After switching to secukinumab combined with HAART, the symptoms of psoriatic arthritis resolved rapidly after four weeks, with a Disease Activity Index for Psoriatic Arthritis score of 0. The time to achieve psoriasis area and severity index 40, 75, 90, and 100 were 2, 4, 8, and 29 weeks. The treatment was maintained for 1 year with no adverse reactions. Regarding the stable CD4+ T lymphocyte count and the viral load, administering anti-IL-17 monoclonal antibodies is an effective treatment option for psoriasis patients.


Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa.
Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3-15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5-13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0-13.8) at 6 months (n = 90), and 16.2 (IQR 9.6-20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels < or = 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported < or = 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8-94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95% CI, 1.27-119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95% CI, 0.02-0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting.


Poor outcome for patients with gastric cancer and lung metastases treated with ramucirumab and paclitaxel.
The aim of this report is to investigate the activity of ramucirumab in combination with paclitaxel in patients with metastatic gastric cancer (GC) and lung metastases. We retrospectively reviewed clinical data from patients with GC treated in second line with ramucirumab and paclitaxel according to the presence or not of lung metastases. Thirty-one patients were eligible. Five (16.1%) patients had lung metastases. The median progression-free survival was 156 days in patients without lung metastases compared with 54 days in patients with lung metastases. The median survival also showed a trend in favour of patients without lung metastases. Despite the small number of patients and the retrospective nature of the data, our analysis showed relatively poor efficacy of ramucirumab plus paclitaxel as a second-line treatment in patients with lung metastases from GC. Further studies are required to evaluate novel treatments in this subset of patients.


Snip punctoplasty offers little additive benefit to lower eyelid tightening in the treatment of pure lacrimal pump failure.
Lacrimal pump failure refers to epiphora due to reduced tear outflow in the presence of a patent lacrimal drainage system and well-positioned puncta. This condition has been managed with dacryocystorhinostomy and lower eyelid tightening, which carry success rates of 50-94% and 84-91%, respectively. In this retrospective study, 23 eyes with symptomatic epiphora attributed to lacrimal pump failure underwent the lateral tarsal strip procedure and lower eyelid snip punctoplasty, and 20 eyes (87%) experienced complete or nearly complete resolution of tearing. This success rate is quite similar to that of prior studies of eyelid tightening alone for lacrimal pump failure, suggesting that the addition of the snip punctoplasty may not offer any additional benefit in patients with little or no punctal stenosis. All patients displayed some degree of lower eyelid laxity on lid distraction testing preoperatively, and those with only mild lid laxity responded at least as well as those with more severe laxity.


Novel bioactive clerodane diterpenoids from the leaves and twigs of Casearia sylvestris.
Fractionation of a methanol extract of the leaves and twigs of Casearia sylvestris, as directed by activity against KB cell cytotoxicity, led to the isolation of three novel clerodane diterpenoids, casearvestrins A-C (1-3). The structures of 1-3 were deduced from one- and two-dimensional NMR experiments, including relative stereochemical assignments based on ROESY correlations and COSY coupling constants. All three compounds displayed promising bioactivity, both in cytotoxicity assays against a panel of tumor cell lines and in antifungal assays via the growth inhibition of Aspergillus niger in a disk diffusion assay.


Visualization of interphase chromosomes.
Using a modified Giemsa-banding technique we have observed what appear to be chromosomes during interphase in nuclei from Allium cepa root tips and Chinese hamster cells (CHO line). During telophase through G1 chromosomes progressively uncoil and decondense. During S chromosomes are comparatively decondensed, but some segments have structure similar to chromosomes in G1 and G2. During G2 the chromosomes progressively recondense and coil in apparent preparation for prophase. Although specific structural modifications of chromosomes occur in G1, Sand G2 nuclei, chromosomes appear never to decondense to the point that they lose their 3-dimensional integrity, but remain in distinct domains throughout interphase.


Model of synchronized epileptiform bursts induced by high potassium in CA3 region of rat hippocampal slice. Role of spontaneous EPSPs in initiation.
1. We constructed a computer model of the in vitro CA3 region of the rat hippocampal slice bathed in a high-potassium medium. Our aim was to understand better the mechanisms of initiation of synchronized bursts and the processes that regulate the interburst interval in the experimental system. 2. Our model began with a previously published model of the longitudinal CA3 hippocampal slice. The model contains three interconnected cell populations: 9,000 (excitatory) pyramidal cells; 450 inhibitory cells whose postsynaptic action is somatic and decays quickly, corresponding to chloride-dependent inhibition mediated by gamma-aminobutyric acid (GABA)A channels, and 450 inhibitory cells whose postsynaptic action is dendritic, of delayed onset and long lasting, that corresponds to K-dependent inhibition mediated by GABAB channels. 3. The model was then modified to account for specific features of the high-K experimental system: 1) the pyramidal cells do not generate intrinsic bursts; 2) EIPSP(CI) and EK are both shifted in a depolarizing direction; 3) spontaneous (i.e., not caused by presynaptic firing) excitatory postsynaptic potentials (EPSP)s were included; and 4) a steady current was injected into the pyramidal cells to depolarize them. 4. This model generates synchronized population bursts with interburst intervals of approximately 1.0-1.5 s. Bursts in individual pyramidal cells are preceded by barrages of EPSPs. These results agree with experiment. 5. Our model agrees with the following additional experiments: 1) synchronized bursts are abolished by partial blockade of excitatory synapses; 2) burst frequency is increased by partial blockade of a slow-intrinsic-K conductance; and 3) blockade of chloride-dependent inhibition leads to bursts of longer duration with longer interburst intervals. 6. The basic structural features of this model are similar to, but not identical to, the model of the disinhibited hippocampal slice. Spontaneous EPSPs appear to be critical in the high-K system for initiating, but not for synchronizing, population bursts. The experimental data and simulation results raise interesting questions about the role of spontaneous EPSPs in initiating synchronized discharges in other epileptic systems and on the possible role of spontaneous EPSPs in the normal brain.


Simultaneous nitrification, denitrification, and phosphorus removal in single-tank low-dissolved-oxygen systems under cyclic aeration.
Simultaneous nitrification and denitrification (SND or SNdN) may occur at low dissolved oxygen concentrations. In this study, bench-scale (approximately 6 L) bioreactors treating a continuous feed of synthetic wastewater were used to evaluate the effects of solids retention time and low dissolved oxygen concentration, under cyclic aeration, on the removal of organics, nitrogen, and phosphorus. The cyclic aeration was carried out with repeated cycles of 1 hour at a higher dissolved oxygen concentration (HDO) and 30 minutes at a lower (or zero) dissolved oxygen concentration (LDO). Compared with aeration at constant dissolved oxygen concentrations, the cyclic aeration, when operated with proper combinations of HDO and LDO, produced better-settling sludge and more complete nitrogen and phosphorus removal. For nitrogen removal, the advantage resulted from the more readily available nitrate and nitrite (generated by nitrification during the HDO period) for denitrification (during the LDO period). For phosphorus removal, the advantage of cyclic aeration came from the development of a higher population of polyphosphate-accumulating organisms, as indicated by the higher phosphorus contents in the sludge solids of the cyclically aerated systems. Nitrite shunt was also observed to occur in the LDO systems. Higher ratios of nitrite to nitrate were found in the systems of lower HDO (and, to less dependency, higher LDO), suggesting that the nitrite shunt took place mainly because of the disrupted nitrification at lower HDO. The study results indicated that the HDO used should be kept reasonably high (approximately 0.8 mg/L) or the HDO period prolonged, to promote adequate nitrification, and the LDO kept low (< or =0.2 mg/L), to achieve more complete denitrification and higher phosphorus removal. The above findings in the laboratory systems find strong support from the results obtained in full-scale plant implementation. Two plant case studies using the cyclic low-dissolved-oxygen aeration for creating and maintaining SND are also presented.


Oxygen radical production and thiol depletion are required for Ca(2+)-mediated endogenous endonuclease activation in apoptotic thymocytes.
Glucocorticoid hormones stimulate apoptosis in thymocytes via a mechanism that involves changes in intracellular Ca2+, and exogenous Ca2+ can also directly promote the nuclear alterations of apoptosis (lamin degradation and chromatin cleavage) in isolated nuclei. Here we report that glucocorticoid treatment resulted in the production of reactive oxygen species and the depletion of reduced glutathione. Separation of apoptotic cells on Percoll gradients demonstrated that both effects selectively occurred in thymocytes undergoing apoptosis. Moreover, glucocorticoid-induced endonuclease activation was partially blocked by the antioxidant N-acetyl-L-cysteine. Although abrogation of methylprednisolone-induced Ca2+ increases using the intracellular Ca2+ buffer 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid resulted in inhibition of endonuclease activation, it failed to prevent GSH depletion. However, N-acetyl-L-cysteine almost completely blocked methylprednisolone-induced elevations in cytosolic calcium levels, indicating that oxidative stress was playing a role in the Ca2+ response. Our results support the idea that oxidative stress is a key component of the apoptotic effector pathway in thymocytes, and that it interacts, at least in part, with the Ca2+ response.


Genetic confirmation of 2 independent genes for resistance to soybean mosaic virus in J05 soybean using SSR markers.
J05 soybean was previously identified to carry 2 independent genes, Rsv1 and Rsv3, for "soybean mosaic virus" (SMV) resistance by inheritance and allelism studies. The objective of this research was to confirm the 2 genes in J05 using molecular markers so that a marker-assisted selection can be implemented. The segregation of F(2) plants from J05 x Essex exhibited a good fit to a 3:1 ratio when inoculated with SMV G1. Three simple sequence repeat (SSR) markers near Rsv1, Satt114, Satt510, and Sat_154, amplified polymorphic DNA fragments between J05 and Essex and were closely linked to the gene on soybean molecular linkage group (MLG) F, thus verifying the presence of Rsv1 in J05 for resistance to SMV G1. The presence of Rsv3 in J05 was confirmed by 2 closely linked SSR markers on MLG B2, Satt726 and Sat_424, in F(2:3) lines that were derived from the SMV G1-susceptible F(2) plants and segregated in a 1:2:1 ratio for reaction to SMV G7. Two closely linked markers for Rsv4, Satt296 and Satt542, segregated independently of SMV resistance, indicating the absence of Rsv4 in J05. These SSR markers for Rsv1 and Rsv3 can serve as a useful molecular tool for selection and pyramiding of genes in J05 for SMV resistance.


Quality initiatives: measuring and managing the procedural competency of radiologists.
Many regulatory and oversight groups require that the professional performance of radiologists be evaluated on an ongoing basis. Although the diagnostic accuracy of radiologists is routinely measured at most institutions by means of peer review processes, systems for evaluating procedural competency are not widely available. Consequently, technical skills are seldom, if ever, evaluated or managed. The key elements of a system for evaluating procedural competency include the following: (a) clear definition of all elements of a transparent evaluation process; (b) definition of standards for training and credentialing and options for maintenance of competency certification in interventional procedures; (c) collection and analysis of process and outcomes metrics; (d) multisource feedback on procedural, patient care, and safety skills; and (e) an effective, anonymous process for managing radiologists in whom deficiencies are identified. Although no ideal system for evaluating procedural competency currently exists, inclusion of these elements goes a long way toward facilitating the introduction of a simple process for providing appropriate feedback to procedural radiologists, acknowledging excellence, and identifying and managing deficiencies if they occur.


Risk factors for meniscectomy after meniscal repair.
Previous research suggests that a substantial percentage of meniscal repairs fail, resulting in a subsequent meniscectomy. Risk factors for failure have been investigated using small cohorts, providing ambiguous results. To measure the frequency of and elucidate risk factors for subsequent meniscectomies after meniscal repair using a large study population from multiple surgical centers. Case-control study; Level of evidence, 3. A total of 9529 patients who underwent 9609 outpatient meniscal repairs between 2003 and 2010 were identified from a statewide database of all ambulatory surgery in New York. Patients who subsequently underwent a meniscectomy were then identified. A Cox regression analysis was used to calculate the hazard ratio and 95% confidence intervals. The model included patient age, sex, comorbidities, concomitant arthroscopic procedures, laterality of the meniscus, and surgeon's yearly meniscal repair volume. The overall frequency of subsequent meniscectomies was 8.9%. Patients were at a decreased risk for subsequent meniscectomies if they underwent a concomitant anterior cruciate ligament (ACL) reconstruction (P < .001). Patients undergoing isolated meniscal repairs (without concomitant ACL reconstruction) were at a decreased risk if they were older (P < .001), had a lateral meniscal injury (P = .002), or were operated on by a surgeon with a higher annual meniscal repair volume (>24 cases/year; P < .001). A meniscectomy after meniscal repair is performed infrequently, supporting the notion that repairing a meniscus is a safe and effective procedure in the long term. The risk for undergoing subsequent meniscectomies is decreased in patients undergoing a concomitant ACL reconstruction, in cases of isolated meniscal repairs for patients of older age, and in patients undergoing meniscal repair by surgeons with a high case volume.


Minimal change disease in a patient receiving IFN-alpha therapy for chronic hepatitis C virus infection.
Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic syndromes. The principal types of renal disorders associated with chronic HCV infection are cryoglobulinemia or noncryoglobulinemic membranoproliferative glomerulonephritis (MPGN). Interferon-alpha (IFN-alpha) may precipitate or exacerbate the occurrence of MPGN. Our patient was a 32-year-old man who tested positive for HCV in July 1997. The patient was treated with IFN-alpha in another medical center for 6 months because his liver biopsy showed chronic active hepatitis. In December 1998, he applied to our clinic for a follow-up examination. The level of aspartate aminotransferase (AST) was 44 U/L, and that of alanine aminotransferase (ALT) was 69 U/L. HCV RNA was positive in serum, and chronic HCV infection was detected by liver biopsy. IFN-alpha therapy (5 million U/day) was administered for 6 months longer. In May 1999, the patient came to our polyclinic with edema of the feet and legs. We detected proteinuria, serum cholesterol of 269 mg/dl, AST of 50 U/L, ALT of 41 U/L, serum total protein of 3.4 g/dl, serum albumin of 1.2 g/dl, positive cryoglobulin, and urine protein of 9.84 g/day. Cryoglobulinemic MPGN was suspected and kidney biopsy was performed, resulting in a diagnosis of minimal change disease (MCD).


Pancreatic autoantibodies and CD14+CD16+ monocytes subset are associated with the impairment of ß-cell function after simultaneous pancreas-kidney transplantation.
Pancreatic autoantibodies (AAb) has been associated with a worse pancreas graft survival after simultaneous pancreas-kidney transplantation (SPK). However, due to the variable time for AAb to become positive and the lack of early biomarkers suggesting such autoimmune activation, the mechanisms leading ß-cell destruction remain uncertain. The present study aimed to evaluate the association between post-transplant AAb and the functional impairment of the pancreatic ß-cell and also the association of such AAb with inflammation after SPK. In a longitudinal study, we analyzed the impact of post-transplant glutamic acid decarboxylase (GAD-65) and the insulinoma-associated autoantigen 2 (IA-2) AAb on pancreas graft function. Serum Hb1Ac and C-peptide (C-pep) were longitudinally compared between a group with positive posttransplant AAb (AAb+; n = 40) and another matched group with negative AAb (AAb-; n = 40) until the fifth year following seroconversion. In the cross-sectional analysis, we further evaluated the systemic signatures of inflammation by measuring pro-inflammatory CD14+CD16+ monocytes by flow-cytometry and interleukin 17-A serum levels in 38 SPK recipients and ten healthy controls. In the longitudinal study, patients with AAb+ showed higher levels of Hb1Ac (p<0.001) and lower C-pep levels (p<0.001) compared to those who remained AAb- throughout the follow-up. In the cross-sectional study, AAb+ patients showed a higher percentage of CD14+CD16+ monocytes compared with those with AAb- and the healthy controls (6.70±4.19% versus 4.0±1.84% and 3.44±0.93%; p = 0.026 and 0.009 respectively). Also, CD14+CD16+ monocytes correlated with Hb1Ac and C-pep serum levels. Multivariate logistic regression showed that posttransplant AAb+ was independently associated with a higher percentage of pro-inflammatory monocytes (adjusted-OR 1.59, 95%CI 1.05-2.40, p = 0.027). The group of patients with positive AAb also showed higher levels of IL17A as compared with the other groups (either healthy control or the negative AAb subjects). In conclusion, pancreatic AAb+ after SPK were not only associated with higher Hb1Ac and lower c-peptide serum levels but also with an increased percentage of CD14+CD16+ monocytes and higher levels of circulating IL17-A.


Decreased interleukin-37 expression in Vogt-Koyanagi-Harada disease and upregulation following immunosuppressive treatment.
Interleukin-37 (IL-37) is emerging as an important inhibitor of immune response. This study was set up to investigate the expression of IL-37 in Vogt-Koyanagi-Harada (VKH) disease and to explore its possible regulatory role during inflammation. Twenty-four untreated active VKH patients, 10 VKH patients receiving corticosteroids and cyclosporin A (CsA), and 35 healthy controls were included in this study. IL-37 expression in lipopolysaccharides (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from these 3 groups was assayed by real-time polymerase chain reaction (RT-PCR) and flow cytometry. Cytokines in the supernatants of stimulated PBMCs and CD4(+) T cells were assayed by enzyme-linked immunosorbent assay (ELISA). Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation were measured by flow cytometry. VKH patients showed a decreased IL-37 and IL-27 expression and increased IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in PBMC culture supernatants. IL-37 significantly inhibited the production of IL-1β, IL-6, and TNF-α, but induced IL-27 expression. VKH patients treated with corticosteroids combined with CsA showed a regression of the intraocular inflammation, and treatment was associated with an enhanced IL-37 production. IL-37 did not affect the production of IL-17, interferon-gamma (IFN-γ), or IL-10 from CD4(+) T cells. The present study suggests that a decreased IL-37 expression in VKH patients is associated with a reduced control of the inflammatory response. Treatment of VKH patients with corticosteroids and CsA is associated with an increased expression of IL-37, which suggests that corticosteroids and CsA may partly exert their immunosuppressive effect by upregulating IL-37 production.


Broad Phylogenetic Diversity Associated with Nitrogen Loss through Sulfur Oxidation in a Large Public Marine Aquarium.
Denitrification by sulfur-oxidizing bacteria is an effective nitrate removal strategy in engineered aquatic systems. However, the community taxonomic and metabolic diversity of sulfur-driven denitrification (SDN) systems, as well as the relationship between nitrate removal and SDN community structure, remains underexplored. This is particularly true for SDN reactors applied to marine aquaria, despite the increasing use of this technology to supplement filtration. We applied 16S rRNA gene, metagenomic, and metatranscriptomic analyses to explore the microbial basis of SDN reactors operating on Georgia Aquarium's Ocean Voyager, the largest indoor closed-system seawater exhibit in the United States. The exhibit's two SDN systems vary in water retention time and nitrate removal efficiency. The systems also support significantly different microbial communities. These communities contain canonical SDN bacteria, including a strain related to Thiobacillus thioparus that dominates the system with the higher water retention time and nitrate removal but is effectively absent from the other system. Both systems contain a wide diversity of other microbes whose metagenome-assembled genomes contain genes of SDN metabolism. These include hundreds of strains of the epsilonproteobacterium Sulfurimonas, as well as gammaproteobacterial sulfur oxidizers of the Thiotrichales and Chromatiales, and a relative of Sedimenticolathiotaurini with complete denitrification potential. The SDN genes are transcribed and the taxonomic richness of the transcript pool varies markedly among the enzymatic steps, with some steps dominated by transcripts from noncanonical SDN taxa. These results indicate complex and variable SDN communities that may involve chemical dependencies among taxa as well as the potential for altering community structure to optimize nitrate removal.IMPORTANCE Engineered aquatic systems such as aquaria and aquaculture facilities have large societal value. Ensuring the health of animals in these systems requires understanding how microorganisms contribute to chemical cycling and waste removal. Focusing on the largest seawater aquarium in the United States, we explore the microbial communities in specialized reactors designed to remove excess nitrogen through the metabolic activity of sulfur-consuming microbes. We show that the diversity of microbes in these reactors is both high and highly variable, with distinct community types associated with significant differences in nitrogen removal rate. We also show that the genes encoding the metabolic steps of nitrogen removal are distributed broadly throughout community members, suggesting that the chemical transformations in this system are likely a result of microbes relying on other microbes. These results provide a framework for future studies exploring the contributions of different community members, both in waste removal and in structuring microbial biodiversity.


Effects of flunixin meglumine on the recovery of ischaemic equine colonic mucosa in vitro.
The effects of prostaglandins and nonsteroidal anti-inflammatory drugs (NSAIDs) on repair of equine intestinal mucosa are important since most horses with gastrointestinal diseases are routinely treated with NSAIDs, such as flunixin meglumine (FM), and these drugs can be toxic to equine gastrointestinal mucosa. Flunixin meglumine would not affect recovery of equine colonic mucosa in vitro, 18 h after a reversible ischaemic injury. In 14 anaesthetised horses, a segment of pelvic flexure was subjected to 2 h of ischaemia and the horses were allowed to recover for 18 h. Seven horses received normal saline and 7 received FM, 1.1 mg/kg bwt i.v., at the end of ischaemia and 12 h later. Colonic mucosa was harvested during a second anaesthesia, 18 h after recovery from ischaemia and then horses were subjected to euthanasia. Transepithelial electrical resistance (TER) and transepithelial flux of tritiated mannitol were used to measure mucosal permeability during 4 h of incubation in Ussing chambers, with the following in vitro treatments: 1) no addition, 2) FM 14 µmol/l as powder, 3) FM 14 µmol/l in injectable form and 4) diluent for injectable FM. Histomorphological changes were assessed by light microscopy. There were no significant differences in any of the measurements between saline and FM treated horses. The mucosal height of the ischaemic FM tissues incubated in diluent was significantly decreased compared to the nonischaemic tissues. Flunixin meglumine did not adversely affect barrier integrity in ischaemic equine colonic mucosa.


Concordance of ATM (ataxia telangiectasia mutated) immunohistochemistry between biopsy or metastatic tumor samples and primary tumors in gastric cancer patients.
ATM (ataxia telangiectasia mutated) is one of several DNA repair proteins that are suggested to sensitize tumor cells to the poly(ADP-ribose) polymerase inhibitor olaparib when deficient. The aim of this study was to assess the spatiotemporal concordance of ATM immunohistochemistry (IHC) in gastric cancer in order to determine if measurements made at the level of various sample types and times could be inferred as having the potential to be relevant to treatment decisions made at the patient level. Two independent cohorts composed of 591 gastric cancer patients divided into a gastrectomy cohort (n = 450) and a metastasis cohort (n = 141) were used in this study. A total of 2,705 ATM IHC samples were examined, including 450 whole tissue, 3 sets of 450 tissue microarray (TMA), 301 biopsy, 222 metastatic tumor and 2 additional whole tissue samples of 50 cases from the gastrectomy cohort, and 141 pairs of primary and metastatic tumors from the metastasis cohort. The prevalence of ATM negativity was 13.1% in biopsies, 13.9, 15.1, and 16.0% in TMAs and 15.9% in whole tissue samples of the gastrectomy cohort, and 21.4% in primary tumor and 21.5% in metastatic tumor samples of the metastasis cohort. coefficients were 0.341 for biopsy, 0.572 as the average of 3 TMAs and 0.415 for the largely synchronous metastatic tumors of the gastrectomy cohort, and 0.153 for the largely asynchronous metastatic tumors of the metastasis cohort. Using whole tissue sections from tumor resections or primary tumor, respectively, as the reference standards, specificity and sensitivity were 91.6 and 41.0% for biopsy, 93.9 and 61.9% as the average of 3 TMAs, and 86.6 and 58.8% for metastatic tumors of the gastrectomy cohort and 81.7 and 33.3% for metastatic tumors of the metastasis cohort, respectively. Although we have demonstrated that the IHC assay for ATM was robust and reproducible in gastric tumor samples, we have also found that measurements were subject to significant discordance across multiple sample types from the same patient. Further work will be necessary to determine if classification may be made more consistent by multiple sampling. However, the lack of agreement between primary and asynchronous metastatic samples suggests that such sampling would need to be performed at the time of any treatment decision.


A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest.
Currently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions. Affymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic cancer. Patients with high-risk scores had significantly higher risk of death compared to patients with low-risk scores (HR 2.27, p = 0.002). When the 13-gene score was combined with lymph node status the risk-score further discriminated the length of patient survival time (p<0.001). Patients with a high-risk score had poor survival independent of nodal status; however, nodal status increased predictability for survival in patients with a low-risk gene signature score (low-risk N1 vs. low-risk N0: HR = 2.0, p = 0.002). While AJCC stage correlated with patient survival (p = 0.03), the 13-gene score was superior at predicting survival. Of the 13 genes comprising the predictive model, four have been shown to be important in PDAC, six are unreported in PDAC but important in other cancers, and three are unreported in any cancer. We identified a 13-gene expression signature that predicts survival of PDAC patients and could prove useful for making treatment decisions. This risk score should be evaluated prospectively in clinical trials for prognostication and for predicting response to chemotherapy. Investigation of new genes identified in our model may lead to novel therapeutic targets.


Implementation of a quality assurance instrument (Preffi 1.0) to improve the effectiveness of health promotion in The Netherlands.
This paper describes the design and outcomes of implementing Preffi 1.0, a quality assurance instrument for health promotion (HP) interventions, among Dutch HP professionals. The Preffi instrument promotes a systematic way of working that is driven by evidence, which is expected to lead to high-quality projects and better outcomes. Implementation interventions included nationwide activities aimed at awareness of and positive attitudes toward the instrument, and an intensive 5-day programme for a self-selected sample aimed to enhance self-efficacy and use. Effects of the nationwide activities were measured in two independent representative samples of Dutch HP professionals (N = 120 and 316, respectively), while a cohort design was used to measure the effects of the training programme. The Theory of Planned Behavior was used to guide both the interventions and the study. While the nationwide implementation activities raised awareness of Preffi and contributed to a more positive attitude towards the instrument, a significant increase in its use required a more intensive training programme. Attitude was especially influenced by the perceived value and necessity of a systematic approach, and the usefulness of the instrument. Health managers in The Netherlands failed to stimulate a systematic implementation of Preffi, even though the embeddedness of Preffi in the quality system of a HP team was found to be a major predictor of its implementation. The study showed that determinants of the implementation stages vary by stage.


Biological aging alters circadian mechanisms in murine adipose tissue depots.
Biological aging alters the metabolism and volume of adipose tissue depots. Recent evidence suggests that circadian mechanisms play a role in promoting adipogenesis, obesity, and lipodystrophy. The current study compared cohorts of younger (5-9 months) and older (24-28 months) C57BL/6 mice as a function of biological age and circadian time. Advanced age significantly reduced the weight of the brown, epididymal, inguinal, and retroperitoneal adipose depots but not total body weight. The older mice reduced their physical activity by >50% and delayed their activity initiation after light offset. The expressed transcriptome in brown and white adipose depots and liver of both cohorts displayed evidence of circadian rhythmicity; however, the oscillating mRNAs differed significantly between age groups and across tissues. The amplitude of Cry1, a component of the negative arm of the circadian apparatus, and downstream regulators such as Rev-erbα were elevated in the older relative to the younger cohorts as a function of circadian time. Overall, transcript levels differed significantly for 557 (inguinal adipose), 1,016 (liver), and 1,021 (brown adipose) expressed sequences between the cohorts as a function of age. These included transcripts encoding proteins within the canonical and non-canonical Wnt pathways. Since the Wnt pathway regulates adipose stem cell differentiation and shares a critical enzyme, glycogen synthase kinase 3β, with the circadian mechanism, the intersection between these two fundamental regulatory mechanisms merits further investigation with respect to biological aging of adipose tissues.


Amelioration of ischemia-reperfusion induced functional and biochemical deficit in mice by Ocimum kilimandscharicum leaf extract.
The genus Ocimum (family Lamiaceae) has been revered for its diverse biological activities. Various species have been used traditionally to treat CNS disorders and are proven to have neuroprotective effect that is often attributed to their significant antioxidant activity. Ocimum kilimandscharicum (Karpoora Thulasi), a prominent member of this genus is reported to have marked antioxidant activity but its neuroprotective potential has not been explored. Thus, present study was designed to evaluate the cerebroprotective effect of O. kilimandscharicum leaf extract (OKLE) in mice against ischemia reperfusion (I-R) induced brain injury. Bilateral common carotid artery occlusion (BCCAO) for 15min followed by 24h reperfusion was used to induce brain damage in Swiss Albino mice. Animals were treated with OKLE (200 and 400mg/kg, po) once daily for 7days after I-R. Morris water maze and elevated plus maze tests were used to assess long and short term memory while neurological severity score was used to determine motor coordination. Histopathological evaluation (TTC staining) along with brain biochemical parameters (TBARS, reduced GSH and SOD activity) were determined to outline neuroprotective mechanism of OKLE. I-R resulted in marked cognitive impairments, motor incoordination in mice, significant brain damage and increased oxidative stress. Treatment with OKLE produced functional recovery in mice which is manifested by improved memory and motor coordination; reduced cerebral infarct size and brain oxidative stress (TBARS levels) and elevated endogenous antioxidants (reduced GSH and SOD activity). In addition, OKLE showed DPPH radical scavenging and reducing power in-vitro. These results show that O. kilimandscharicum mitigated the neurodegenerative changed induced by I-R in mice probably due to its antioxidant activity.


Rural men and mental health: their experiences and how they managed.
There is a growing awareness that a primary source of information about mental health lies with the consumers. This paper reports on a study that interviewed rural men with the aim of exploring their mental health experiences within a rural environment. The results of the interviews are a number of stories of resilience and survival that highlight not only the importance of exploring the individuals' perspective of their issues, but also of acknowledging and drawing on their inner strengths. Rural men face a number of challenges that not only increase the risk of mental illness but also decrease the likelihood of them seeking and/or finding professional support. These men's stories, while different from each other, have a common thread of coping. Despite some support from family and friends, participants also acknowledged that seeking out professional support could have made the recovery phase easier. Mental health nurses need to be aware, not only of the barrier to professional support but also of the significant resilience that individuals have and how it can be used.


The "One Shot" Diode Laser Stapedotomy.
The purpose of this study was to evaluate the effectiveness and the safety of diode laser stapedotomy, through the functional results analysis. A total of 179 primary cases of otosclerosis that had been operated on with a diode laser technique from 2004 to 2012 were retrospectively reviewed. Preoperative, 1 month postoperative, and late annual follow-up audiograms (up to 8 years) were obtained in all the cases. Mean preoperative and 1 month postoperative pure-tone average (500-1000-2000-4000 Hz) bone conduction thresholds (PTA-BCs), air conduction (AC) hearing outcomes for 8 kHz and mean postoperative air-bone gap (PTA-ABG) closure were analyzed. The mean preoperative (pre) PTA-BC was 24.22 dB (±8.7 SD) whereas the mean postoperative (post) PTA-BC was 21.11 dB (±9.1 SD). The mean preoperative 8 kHz AC was 56.41 dB (±22.86 SD) and the postoperative 8 kHz AC was 52.56 dB (±24.35 SD). A statistically significant improvement of the PTA-BC post and of the postoperative 8 kHz AC was observed. The 1 month ABG closure within 10 dB in 89.02% of the patients and within 20 dB in 97.69% of the patients was obtained with statistically significant stability over long-term follow-up. No major complications occurred in the series. The use of diode laser with high power and short time exposure as setup can be considered a safe, precise, and useful tool in stapes surgery.


Clinical utility of the Chinese Strengths and Weaknesses of ADHD-Symptoms and Normal-Behaviors questionnaire (SWAN) when compared with DISC-IV.
Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing child and adolescent psychiatric disorder. Early identification and prompt treatment are essential. Rating scales are commonly used by clinicians and researchers to assess ADHD children. In the current study, we aimed to examine the clinical utility of the Chinese version of the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviors (SWAN) questionnaire. We validated its subscale scores against the Diagnostic Interview Schedule for Children Version IV (DISC-IV) and looked into its ability to identify ADHD in a psychiatric clinic setting. We also tested age and gender effects on SWAN scores. Specific subscale cutoff scores of SWAN were subsequently determined. A total of 290 children aged 6-12 years old studying in local mainstream primary schools were recruited from a clinic setting and interviewed with the parent version of DISC-IV. Their parents and teachers completed the corresponding version of SWAN. Both parent and teacher versions of SWAN were found to have good concurrent validity with DISC-IV. It could identify ADHD well in a clinic sample. Gender-specific cutoff scores were determined. Sensitivities and specificities were found to be satisfactory. SWAN was also found to perform equally well in identifying ADHD in those with and without comorbid Autistic Spectrum Disorder. SWAN was proven to be a useful tool to aid the assessment of ADHD in a clinic sample.


Training auscultatory skills: computer simulated heart sounds or additional bedside training? A randomized trial on third-year medical students.
The present study compares the value of additional use of computer simulated heart sounds, to conventional bedside auscultation training, on the cardiac auscultation skills of 3rd year medical students at Oslo University Medical School. In addition to their usual curriculum courses, groups of seven students each were randomized to receive four hours of additional auscultation training either employing a computer simulator system or adding on more conventional bedside training. Cardiac auscultation skills were afterwards tested using live patients. Each student gave a written description of the auscultation findings in four selected patients, and was rewarded from 0-10 points for each patient. Differences between the two study groups were evaluated using student's t-test. At the auscultation test no significant difference in mean score was found between the students who had used additional computer based sound simulation compared to additional bedside training. Students at an early stage of their cardiology training demonstrated equal performance of cardiac auscultation whether they had received an additional short auscultation course based on computer simulated training, or had had additional bedside training.


Induction of liver growth in normal mice by infusion of hepatocyte growth factor/scatter factor.
Hepatocyte growth factor/scatter factor (HGF/SF) is a potent stimulator of DNA synthesis in a variety of epithelial cells, including hepatocytes, and has been implicated in liver regeneration. We show here that combining dextran sulfate with HGF/SF markedly increases the plasma concentrations of HGF/SF that are achieved during intraperitoneal infusion. Three days of administration of HGF/SF by this mechanism caused a dose-dependent increase in liver wet weight. Mitotic figures were rarely observed in control livers but were abundant in livers exposed to HGF/SF, and liver DNA content was elevated. Serum levels of triglycerides, cholesterol, total protein, and albumin were also dose dependently increased, whereas alkaline phosphatase was reduced. From these data we conclude 1) that combining HGF/SF with dextran sulfate provides a novel method for delivering HGF/SF in a continuous manner, 2) that HGF/SF can induce liver growth in an intact animal, and 3) that HGF/SF-induced liver enlargement is associated with changes in serum biochemistry.


Behavioral effects of salbutamol and/or L-(+)-ascorbic acid in the mouse after single and multiple dosing.
The acute and chronic effects of salbutamol alone and L-(+)-ascorbic acid alone and in combination were evaluated on "open-field" test in mice. Administered singly and acutely (30 min before the test), both salbutamol (0.003 mmol/kg i.p.) and L-(+)-ascorbic acid (0.35-0.71 and 1.42 mmol/kg i.p.) significantly reduced ambulation scores. This decrease was higher in L-(+)-ascorbic acid - than in salbutamol-treated mice. Rearing behavior was significantly increased only in salbutamol-treated animals. In animals treated chronically (once a day for 15 days) the depression of salbutamol-induced ambulation was more marked than in mice treated acutely. This decrease was partially reversed by L-(+)-ascorbic acid treatment. With respect to rearing scores, a significant increase was found after salbutamol and L-(+)-ascorbic acid administered alone or in combination. In conclusion, these experiments show that salbutamol induces a direct effect on behavior, that is to reduce motor activity, being the reduction more marked after chronic treatment. The association of the beta 2-agonist with L-(+)-ascorbic acid can attenuate some of the depressant effects of chronic salbutamol administration on behavior.


Efficacy of alcohols and alcohol-based hand disinfectants against human enterovirus 71.
Human enterovirus 71 (HEV71) infections are a significant public health threat in the Asia-Pacific region and occasionally cause severe neurological complications and even death in children. Although good hand hygiene is important for controlling infection, relevant data regarding the efficacy of widely used hand disinfectants against HEV71 are still lacking. To investigate the virucidal activity of alcohols and alcohol-based hand disinfectants against HEV71. A common alcohol-based hand disinfectant (0.5% chlorhexidine gluconate + 70% isopropanol) as well as different concentrations of isopropanol and ethanol were tested for virucidal activity against HEV71 using the suspension and the fingerpad tests. In suspension tests, 85% and 95% ethanol achieved a mean log10 reduction factor in HEV71 titre of >3 and nearly 6, respectively, within 10 min. By contrast, 70% and 75% ethanol and any concentration of isopropanol (70-95%) produced a factor of <1 in this test after the same exposure time. In fingerpad tests, only 95% ethanol showed a mean log10 reduction factor of >4, while both 75% ethanol and a chlorhexidine gluconate-containing formula were ineffective against HEV71 with a mean log10 reduction factor of <1 after a 30 s exposure time. Widely used alcohol-based hand disinfectants based on 70% ethanol or isopropanol have poor effectiveness against HEV71. Ninety-five percent ethanol is the most effective concentration, but still cannot fully inactivate HEV71 and may be impractical for use in many instances. Hand hygiene with alcohol-based hand disinfectants alone is not recommended for preventing HEV71 transmission.


Common and conflicting interests in the engagements between conservation organizations and corporations.
The conservation community increasingly views the corporate sector as a positive force for conservation. Collaborations between corporations and nongovernmental conservation organizations (NGOs) seek to mitigate the negative effects of corporate activities and augment positive conservation outcomes. I reviewed the establishment of corporate social responsibility (CSR) policies by corporations; the emerging focus on environmental practices and sustainability; and the history of engagement between corporations and nongovernmental organizations. I considered the ethical and reputation vulnerabilities of these collaborations, which depend especially on the financial nature of the relationship and reviewed how CSR approaches have influenced corporate practices. I concluded that whereas CSR practices can act to mitigate negative environmental impact, to date they have had limited positive effect on biodiversity conservation.


Experiences of infant-feeding decision-making among urban economically disadvantaged pregnant adolescents.
The aim of this paper is to report a pilot study of influencing factors in disadvantaged urban pregnant adolescents' decision-making about infant-feeding choices. Research related to decision-making among adolescents indicates that attitudinal, social, perceived control, and commitment factors are influential in choosing and initiating breast- or bottle-feeding. However, there is a need for further description of decision-making processes in disadvantaged teenagers before intervention research is done. Focus group interviews with the Theory of Planned Behavior guiding the questioning were used with 14 pregnant adolescents between 18 and 39 weeks of gestation and between the ages of 14 and 18 in two obstetric clinics in Midwestern USA urban teaching hospitals. The majority of adolescents were African-American and primiparae. The experiences of infant-feeding decision-making among pregnant adolescents were captured by two major themes: benefits vs. barriers of breastfeeding and bottle-feeding, and independent choice vs. social influences. A common thread in these themes was ambivalence and uncertainty. The adolescents had both positive and negative attitudes toward methods, with many expressing their desire to combine breast- and bottle-feeding. Many reported the health benefits of breastfeeding, yet identified barriers of pain, public exposure, and the complexity of breastfeeding. They viewed bottle-feeding as automatic and simple, allowing freedom to leave the infant with others. Although adolescents were adamant that choice of feeding method was their independent decision, social and family influences were evident. Consistent with the Theory of Planned Behaviour and other research, attitudes, perceived social influences, and perceived control factors were influential to adolescents when choosing infant feeding methods. The findings suggest that adolescents need education on decision-making, and are being used to fine-tune the interventions of a randomized clinical trial to investigate promoting and supporting breastfeeding among adolescent mothers.


Rifampicin is a candidate preventive medicine against amyloid-β and tau oligomers.
Amyloid-β, tau, and α-synuclein, or more specifically their soluble oligomers, are the aetiologic molecules in Alzheimer's disease, tauopathies, and α-synucleinopathies, respectively. These proteins have been shown to interact to accelerate each other's pathology. Clinical studies of amyloid-β-targeting therapies in Alzheimer's disease have revealed that the treatments after disease onset have little benefit on patient cognition. These findings prompted us to explore a preventive medicine which is orally available, has few adverse effects, and is effective at reducing neurotoxic oligomers with a broad spectrum. We initially tested five candidate compounds: rifampicin, curcumin, epigallocatechin-3-gallate, myricetin, and scyllo-inositol, in cells expressing amyloid precursor protein (APP) with the Osaka (E693Δ) mutation, which promotes amyloid-β oligomerization. Among these compounds, rifampicin, a well-known antibiotic, showed the strongest activities against the accumulation and toxicity (i.e. cytochrome c release from mitochondria) of intracellular amyloid-β oligomers. Under cell-free conditions, rifampicin inhibited oligomer formation of amyloid-β, tau, and α-synuclein, indicating its broad spectrum. The inhibitory effects of rifampicin against amyloid-β and tau oligomers were evaluated in APPOSK mice (amyloid-β oligomer model), Tg2576 mice (Alzheimer's disease model), and tau609 mice (tauopathy model). When orally administered to 17-month-old APPOSK mice at 0.5 and 1 mg/day for 1 month, rifampicin reduced the accumulation of amyloid-β oligomers as well as tau hyperphosphorylation, synapse loss, and microglial activation in a dose-dependent manner. In the Morris water maze, rifampicin at 1 mg/day improved memory of the mice to a level similar to that in non-transgenic littermates. Rifampicin also inhibited cytochrome c release from the mitochondria and caspase 3 activation in the hippocampus. In 13-month-old Tg2576 mice, oral rifampicin at 0.5 mg/day for 1 month decreased amyloid-β oligomer accumulation, tau hyperphosphorylation, synapse loss, and microglial activation, but not amyloid deposition. Rifampicin treatment to 14-15-month-old tau609 mice at 0.5 and 1 mg/day for 1 month also reduced tau oligomer accumulation, tau hyperphosphorylation, synapse loss, and microglial activation in a dose-dependent fashion, and improved the memory almost completely at 1 mg/day. In addition, rifampicin decreased the level of p62/sequestosome-1 in the brain without affecting the increased levels of LC3 (microtubule-associated protein light chain 3) conversion, suggesting the restoration of autophagy-lysosomal function. Considering its prescribed dose and safety in humans, these results indicate that rifampicin could be a promising, ready-to-use medicine for the prevention of Alzheimer's disease and other neurodegenerative diseases.


[Experience in the isolation of salmonellae in foods of different risk categories (author's transl)].
146 samples of pancreatic powder, 208 samples of pasteurized egg albumen, both deep-frozen and spray-dried, and 355 samples of frozen poultry were investigated for the presence of salmonellae. Four pre-enrichment media (lactose broth, nutrient broth, buffered peptone water and tryptone soya broth) and two direct selective enrichment media (dulcitol selenite and tetrathionate) were used. For the pre-enrichment of frozen poultry, buffered peptone water and tryptone soya broth proved to be more satisfactory than lactose broth and nutrient broth. Pre-enrichment of freeze-dried material in a non-selective medium yielded more Salmonella than were obtained by a direct selective enrichment. 16 of 146 samples of freeze-dried pancreatic powder contained salmonellae. Accordingly, tissue and organs of slaughter animals designed for the production of pharmaceutical preparations require regular bacteriological control.


Evaluation of Respiratory Motion Effect on Defect Detection in Myocardial Perfusion SPECT: A Simulation Study.
The objective of this study is to investigate the effects of respiratory motion (RM) on defect detection in Tc-99m sestamibi myocardial perfusion SPECT (MPS) using a phantom population that includes patient variability. Three RM patterns are included, namely breath-hold, slightly enhanced normal breathing, and deep breathing. For each RM pattern, six 4-D NCAT phantoms were generated, each with anatomical variations. Anterior, lateral and inferior myocardial defects with different sizes and contrasts were inserted. Noise-free SPECT projections were simulated using an analytical projector. Poisson noise was then added to generate noisy realizations. The projection data were reconstructed using the OS-EM algorithm with 1 and 4 subsets/iteration and at 1, 2, 3, 5, 7, and 10 iterations. Short-axis images centered at the centroid of the myocardial defect were extracted, and the channelized Hotelling observer (CHO) was applied for the detection of the defect. The CHO results show that the value of the area under the receiver operating characteristics (ROC) curve (AUC) is affected by the RM amplitude. For all the defect sizes and contrasts studied, the highest or optimal AUC values indicate maximum detectability decrease with the increase of the RM amplitude. With no respiration, the ranking of the optimal AUC value in decreasing order is anterior then lateral, and finally inferior defects. The AUC value of the lateral defect drops more severely as the RM amplitude increases compared to other defect locations. Furthermore, as the RM amplitude increases, the AUC values of the smaller defects drop more quickly than the larger ones. We demonstrated that RM affects defect detectability of MPS imaging. The results indicate that developments of optimal data acquisition methods and RM correction methods are needed to improve the defect detectability in MPS.


Three-dimensional evaluation of the alar cinch suture after Le Fort I osteotomy.
Orthognathic surgery has an influence on the overlying soft tissues of the translated bony maxillomandibular complex. Improvements in both function and facial appearance are the goals of surgery. However, unwanted changes to the soft tissues, especially in the nose region, frequently occur. The most common secondary change in the nasolabial region is widening of the alar base. Various surgical techniques have been developed to minimize this effect. The purpose of this study was to evaluate the changes in the nasal region due to orthognathic surgery, especially the alar width and nasal volume, using combined cone beam computed tomography (CBCT) and three-dimensional (3D) stereophotogrammetry datasets. Twenty-six patients who underwent a Le Fort I advancement osteotomy between 2006 and 2013 were included. From 2006 to 2010, no alar base cinch sutures were performed. From 2010 onwards, alar base cinch sutures were used. Preoperative and postoperative documentation consisted of 3D stereophotogrammetry and CBCT scans. 3D measurements were performed on the combined datasets, and the alar base width and nose volume were analyzed. No difference in alar base width or nose volume was observed between patients who had undergone an alar cinch and those who had not. Postoperatively the nose widened and the volume increased in both groups.


Suppression of human synovial cell proliferation by dihomo-gamma-linolenic acid.
Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo-gamma-linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin-1 beta (rIL-1 beta), ASC proliferate and produce PGE. DGLA-enriched medium suppressed both baseline and rIL-1 beta-stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL-1 beta-stimulated cells that were incubated with DGLA exhibited a 14-fold increase in PGE1 (to 25.2 +/- 6.0 ng/ml, mean +/- SD) and a 70% decrease in PGE2 (to 25.2 +/- 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 x 10(-7) M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 +/- 2.0 pmoles versus 4.3 +/- 1.9 pmoles, mean +/- SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acid-enriched cultures (17.8 +/- 3.3 pmoles versus 2.1 +/- 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.


Evaluation of the role of endomyocardial biopsy in 851 patients with unexplained heart failure from 2000-2009.
Endomyocardial biopsy (EMB) is often considered when the pathogenesis of heart failure cannot be determined by noninvasive testing. Uncertainty remains about the diagnostic and clinical use of EMB in various clinical scenarios. We examined the characteristics of a cohort of patients with unexplained heart failure who underwent EMB at a tertiary care medical center. We categorized each patient into a clinical scenario as outlined by the 2007 AHA/ACC/ESC guidelines and determined the number of times EMB provided a diagnosis or altered the clinical course. A total of 851 patients underwent EMB from 2000-2009. Overall, 25.5% of EMBs provided a diagnosis and 22.7% of EMBs changed clinical course. Heart failure associated with unexplained restrictive cardiomyopathy was the most common clinical scenario, comprising 33.6% (286/851) of EMBs, and 84 (29.4%) of these EMBs were diagnostic. EMB for unexplained heart failure of <2 weeks duration had a diagnostic yield at 35% (39/109). There were 4 uncommon scenarios where EMB had a high diagnostic and clinical yield. There were 16 complications for an overall rate of 1.9%. We confirm that EMB is useful in acute onset unexplained cardiomyopathy. We demonstrate a role for EMB in suspected infiltrative disease and in the management of rare clinical scenarios, such as suspected hypersensitivity myocarditis, anthracycline cardiomyopathy, cardiac tumors, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Our results suggest low use of EMB in chronic heart failure that responds to usual care.


Pharmacist-led, primary care-based disease management improves hemoglobin A1c in high-risk patients with diabetes.
We developed and evaluated a comprehensive pharmacist-led, primary care-based diabetes disease management program for patients with Type 2 diabetes and poor glucose control at our academic general internal medicine practice. The primary goal of this program was to improve glucose control, as measured by hemoglobin A1c (HbA1c). Clinic-based pharmacists offered support to patients with diabetes through direct teaching about diabetes, frequent phone follow-up, medication algorithms, and use of a database that tracked patient outcomes and actively identified opportunities to improve care. From September 1999, to May 2000, 159 subjects were enrolled, and complete follow-up data were available for 138 (87%) patients. Baseline HbA1c averaged 10.8%, and after an average of 6 months of intervention, the mean reduction in HbA1c was 1.9 percentage points (95% confidence interval, 1.5-2.3). In predictive regression modeling, baseline HbA1c and new onset diabetes were associated with significant improvements in HbA1c. Age, race, gender, educational level, and provider status were not significant predictors of improvement. In conclusion, a pharmacist-based diabetes care program integrated into primary care practice significantly reduced HbA1c among patients with diabetes and poor glucose control.


Dermatosis neglecta: a report of two cases.
Few cases of dermatosis neglecta have been reported in the medical literature, although the diagnosis is well-known to dermatologists. Recognizing this condition avoids unnecessary, aggressive diagnostic and therapeutic procedures. This case report discusses two cases of this condition in female patients in whom the dermatosis developed as a result of deliberate or unconscious neglect of personal hygiene.


Obesity and inflammation: the effects of weight loss.
Following the discovery of TNF-alpha and leptin as secretory products of adipocytes in the early 1990s, subsequent obesity research focused on the new functional role of adipose tissue, as an active endocrine organ. Many more inflammatory peptides have been linked to adiposity, which ultimately characterised obesity as a state of low-grade systemic inflammation, or 'metaflammation' which may link obesity to its co-morbidities. The aim of the present review is to examine the effects of weight loss on inflammation in overweight and obese, but otherwise healthy, populations. Studies were broadly classified into four types (diet, physical activity, diet and physical activity combined, and surgical interventions) and discussed according to the method used to induce weight loss. All studies measured at least one obesity-related inflammatory marker (ORIM). The overall finding from the present review is that weight loss does improve inflammation in terms of both the inflammatory (C-reactive protein, TNF-alpha, IL-6 and leptin) and anti-inflammatory (adiponectin) ORIM. Within this, the greatest improvements in ORIM are observed in studies achieving a weight loss of at least 10 %. However, a number of methodological issues have been identified as potential limitations within the literature including the sex and age of subjects, sample size, study duration and the assessment of body composition. In conclusion, although a period of weight loss per se is capable of reversing the unfavourable inflammatory profile evident in the obese state, further studies are required to determine the time needed, in which a reduced weight is maintained, in order to benefit from improved inflammatory status long term.


Comparison of Flavobacterium and Sphingobacterium species by enzyme profiles, with use of pattern recognition of two-dimensional fluorescence data.
Enzyme profiles of eight Flavobacterium species and one Sphingobacterium species were compared after using a two-dimensional fluorescence technique. Enzyme contents and corresponding activities were rapidly determined for whole-cell preparations after incubation with a mixture of preselected fluorogenic substrates. A two-dimensional fluorescence spectrum of the resulting product mixture, measured with a video fluorometer, provided a characteristic "fingerprint" for each organism. Comparison of fluorescent spectra was facilitated by a Fourier-transform-based pattern-recognition algorithm and by a clustering technique involving the Pearson product-moment correlation coefficient. F. multivorum, F. thalpophilum, and S. mizutae formed one cluster; F. indologenes, F. spiritivorum, F. odoratum, and F. balustinum formed a second. F. meningosepticum was intermediate between the first and second cluster, whereas F. breve was different from all other strains examined, based on their spectral dissimilarity indices and correlation coefficients.


Impact of single room design on the spread of multi-drug resistant bacteria in an intensive care unit.
Cross-transmission of nosocomial pathogens occurs frequently in intensive care units (ICU). The aim of this study was to investigate whether the introduction of a single room policy resulted in a decrease in transmission of multidrug-resistant (MDR) bacteria in an ICU. We performed a retrospective study covering two periods: between January 2002 and April 2009 (old-ICU) and between May 2009 and March 2013 (new-ICU, single-room). These periods were compared with respect to the occurrence of representative MDR Gram-negative bacteria. Routine microbiological screening, was performed on all patients on admission to the ICU and then twice a week. Multi-drug resistance was defined according to a national guideline. The first isolates per patient that met the MDR-criteria, detected during the ICU admission were included in the analysis. To investigate the clonality, isolates were genotyped by DiversiLab (bioMérieux, France) or Amplified Fragment Length Polymorphism (AFLP). To guarantee the comparability of the two periods, the 'before' and 'after' periods were chosen such that they were approximately identical with respect to the following factors: number of admissions, number of beds, bed occupancy rate, per year and month. Despite infection prevention efforts, high prevalence of MRD bacteria continue to occur in the original facility. A marked and sustained decrease in the prevalence of MDR-GN bacteria was observed after the migration to the new ICU, while there appear to be no significant changes in the other variables including bed occupancy and numbers of patient admissions. Single room ICU design contributes significantly to the reduction of cross transmission of MRD-bacteria.


Cost-Effectiveness of Device-Aided Therapies in Parkinson's Disease: A Structured Review.
Despite optimal dopaminergic treatment most patients in moderate to advanced stages of Parkinson's disease (PD) experience progressively increasing disabilities, necessitating a shift from oral medication to device-aided therapies, including deep brain stimulation (DBS), intrajejunal levodopa-carbidopa infusion (IJLI), and continuous subcutaneous apomorphine infusion (CSAI). However, these therapies are costly, limiting their implementation. To perform a systematic review on cost-effectiveness analyses for device-aided therapies in PD. References were identified by performing a systematic search in the PubMed and Web of Science databases in accordance with the PRISMA statement. In the absence of universal cost-effectiveness definitions, the gross domestic product per capita (GDP) in the country where a study was performed was used as a cut-off for cost-effectiveness based on cost per quality adjusted life year (QALY) gained. In total 30 studies were retrieved. All device-aided therapies improved quality of life compared to best medical treatment, with improvements in QALYs between 0.88 and 1.26 in the studies with long temporal horizons. For DBS, nearly all studies showed that cost per QALY was below the GDP threshold. For infusion therapies only three studies showed a cost per QALY below this threshold, with several studies with long temporal horizons showing costs below or near the GDP threshold. Of the device-aided therapies, DBS can be considered cost-effective, but the majority of infusion therapy studies showed that these were less cost-effective. However, long-term use of the infusion therapies appears to improve their cost-effectiveness and in addition, several strategies are underway to reduce these high costs.


Autophagy Gene Panel-Based Prognostic Model in Myelodysplastic Syndrome.
Abnormal autophagy is related to the pathogenesis and clinical symptoms of myelodysplastic syndrome (MDS). However, the effect of autophagy-related genes (ARGs) on the prognosis of MDS remains unclear. Here, we examined the expression profile of 108 patients with MDS from the GSE58831 dataset, and identified 22 genes that were significantly associated with overall survival. Among them, seven ARGs were screened and APIs were calculated for all samples based on the expression of the seven ARGs, and then, MDS patients were categorized into high- and low-risk groups based on the median APIs. The overall survival of patients with high-risk scores based on these seven ARGs was shorter than patients with low-risk scores in both the training cohort (P = 2.851e-06) and the validation cohort (P = 9.265e-03). Additionally, API showed an independent prognostic indicator for survival in the training samples [hazard ratio (HR) = 1.322, 95% confidence interval (CI): 1.158-1.51; P < 0.001] and the validation cohort (HR = 1.05, 95% CI: 1-1.1; P < 0.01). The area under the receiver operating characteristic curve (AUROC) of API and IPSS were 43.0137 and 66.0274 in the training cohorts and the AUC of the validation cohorts were 41.5361 and 72.0219. Our data indicate these seven ARGs can predict prognosis in patients with MDS and could guide individualized treatment.


Influence of tongue muscle contraction and transmural pressure on nasopharyngeal geometry in the rat.
The mammalian pharynx is a hollow muscular tube that participates in ingestion and respiration, and its size, shape, and stiffness can be altered by contraction of skeletal muscles that lie inside or outside of its walls. MRI was used to determine the interaction between pharyngeal pressure and selective stimulation of extrinsic tongue muscles on the shape of the rat nasopharynx. Pressure (-9, -6, -3, 3, 6, and 9 cmH₂O) was applied randomly to the isolated pharyngeal airway of anesthetized rats that were positioned in a 4.7-T MRI scanner. The anterior-posterior (AP) and lateral diameters of the nasopharynx were measured in eight axial slices at each level of pressure, with and without bilateral hypoglossal nerve stimulation (0.1-ms pulse, 1/3 maximal force, 80 Hz). The rat nasopharynx is nearly circular, and positive pharyngeal pressure caused similar expansion of AP and lateral diameters; as a result, airway shape (ratio of lateral to AP diameter) remained constant. Negative pressure did not change AP or lateral diameter significantly, suggesting that a negative pressure reflex activated the tongue or other pharyngeal muscles. Stimulation of tongue protrudor muscles alone or coactivation of protrudor and retractor muscles caused greater AP than lateral expansion, making the nasopharynx slightly more elliptical, with the long axis in the AP direction. These effects tended to be more pronounced at negative pharyngeal pressures and greater in the caudal than rostral nasopharynx. These data show that stimulation of rodent tongue muscles can adjust pharyngeal shape, extending previous work showing that tongue muscle contraction alters pharyngeal compliance and volume, and provide physiological insight that can be applied to the treatment of obstructive sleep apnea.


Irradiation of GAPDH: a model for environmentally induced protein damage.
Environmental factors, including sunlight, are able to induce severe oxidative protein damage. The modified proteins are either repaired, degraded or escape from degradation and aggregate. In the present study we tested the effect of different sunlight components such as UV-A, UV-B, and infrared radiation on protein oxidation in vitro. We chose glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a model enzyme and analyzed the irradiation-induced enzyme activity loss, fragmentation and aggregation, and quantified various oxidative amino acid modifications. Since gamma-irradiation was used in numerous studies before, we used it for comparative purposes. Infrared radiation was unable to damage GAPDH in the dose range tested (0-1000 J/cm(2)). UV-A led to a decrease in free thiol content, which was connected with a loss in enzyme activity, while only at very high doses could moderate protein aggregation and fragmentation be observed. UV-B (0-2 J/cm(2)) and gamma-irradiation (0-500 Gy) led to a dose-dependent increase in protein modification. Interestingly, UV-B acted on specific amino acids, such as arginine, proline, and tyrosine, whereas gamma-irradiation acted more randomly. The possibility of using the amino acid oxidation pattern as a biomarker of the source of damage is discussed.


Rubidibacter lacunae gen. nov., sp. nov., a unicellular, phycoerythrin-containing cyanobacterium isolated from seawater of Chuuk lagoon, Micronesia.
A unicellular cyanobacterium, designated KORDI 51-2(T), was isolated from surface seawater of Chuuk lagoon, Micronesia. The cells were wine-coloured rods and emitted red fluorescence under green excitation of an epifluorescence microscope. Thus, morphologically, the strain resembled Synechococcus species. However, based on 16S rRNA gene sequence similarities between strain KORDI 51-2(T) and related strains belonging to cyanobacteria, the novel strain was distantly related to members of the 'Halothece' cluster. However, sequence similarities between strain KORDI 51-2(T) and members of the 'Halothece' cluster were very low, ranging from 90.7 to 92.1 %, and phylogenetic analyses showed that the strain formed a distinct branch. Therefore, a polyphasic characterization including morphology, physiology and pigment composition was conducted to elucidate the taxonomic position of strain KORDI 51-2(T). The strain grew within a temperature range of 25-35 degrees C and a salinity range of 2-7 %. The optimal temperature and salinity were about 30 degrees C and 5 %, respectively. Strain KORDI 51-2(T) contained phycoerythrin, and the dominant carotenoid pigments were zeaxanthin, beta-carotene and echinenone. The DNA G+C content was 60.5 mol%. Based on phylogenetic analysis of the 16S rRNA gene sequence, and the physiological data and pigment compositions, strain KORDI 51-2(T) is considered to represent a new genus and novel species of cyanobacteria for which the name Rubidibacter lacunae gen. nov., sp. nov. is proposed. The type strain is KORDI 51-2(T) (=KCTC 40015(T)=UTEX L2944(T)).


Investigation into the seasonal salmonellosis in lactating dairy cattle.
Sporadic salmonellosis has been reported in mature lactating dairy cattle in the southwestern United States and is an intriguing problem in that Salmonella can be cultured from faecal samples of these cattle throughout the year. However, it is pathogenic only during late summer/early autumn and in certain years. We sampled apparently healthy (n=10) and diarrhoeic (n=10) cattle during an outbreak on a 2000 head dairy in 2003. The following year, monthly faecal (from the same 30 head), total mixed ration, water, and pen soil samples were collected for Salmonella culture. No serogroup, serotype, genetic, or antimicrobial susceptibility differences were observed in comparison of isolates from healthy and sick cattle. During year 2 of the study, Salmonella was routinely cultured (although highly variable from month to month) from the cattle and the environment, although no outbreak of salmonellosis was observed.


Epithelial Sodium Channel in Aldosterone-Induced Endothelium Stiffness and Aortic Dysfunction.
Enhanced activation of the endothelial mineralocorticoid receptor contributes to the development of arterial stiffness, which is an independent predictor of cardiovascular disease. Previously, we showed that enhanced endothelium mineralocorticoid receptor signaling in female mice prompts expression and translocation of the α-subunit of the epithelial sodium channel to the endothelial cell (EC) surface (EnNaC) inducing vascular fibrosis and stiffness. Further, amiloride, an epithelial sodium channel antagonist, inhibits vascular fibrosis, remodeling, and stiffness induced by feeding a Western diet high in saturated fat and refined carbohydrates. However, how this occurs remains unknown. Thereby, we hypothesized that endothelial cell-specific EnNaC activation is necessary for aldosterone-mediated endothelium stiffness. To address this notion, EnNaC α-subunit knockout (EnNaC-/-) and wild-type littermate female mice were administrated aldosterone (250 µg/kg per day) via osmotic minipumps for 3 weeks beginning at 25 to 28 weeks of age. In isolated mouse endothelial cells, inward sodium currents were significantly reduced in amiloride controls, as well as in EnNaC-/-. Likewise, aldosterone-induced endothelium stiffness was increased and endothelium-dependent relaxation less in EnNaC-/- versus wild-type. Further, EnNaC-/- mice exhibited attenuated responses to aldosterone infusion, including aortic endoplasmic reticulum stress, endothelium nitric oxide synthase activation, endothelium permeability, expression of proinflammatory cytokines, oxidative stress, and aortic collagen 1 deposition, supporting the notion that αEnNaC subunit activation contributes to these vascular responses.


Antecedents of the attitude towards inter-group reconciliation in a setting of armed conflict.
The concept of Reconciliation as applied to inter-group conflict has come into use only recently. Throughout the history of Psychology, Reconciliation was mostly understood at the individual and inter-personal level. In the present study we shall analyse the roles played by trust, negotiating attitude, legitimacy and ethnocentric attitude over the attitude towards social reconciliation. To this end we studied a group of 188 Colombian civilians living under conditions of real socio-political conflict. A path analysis was performed using the statistical program AMOS whose fit indexes indicate a good fit of the model and a variance of .36. The results show that the variables of trust, negotiating attitude and legitimacy have a significant and positive effect on the reconciliation variable, and significant negative effect on the ethnocentric attitude variable. This study contributes to the integration of a number of variables that facilitate process of social reconciliation, as it explicitly deals with some of the perceptions, attitudes and beliefs which could change the course of a confrontation.


[Pancreas divisum, chronic pancreatitis and diabetes mellitus. Improvement by pancreaticojejunostomy].
The relationship between pancreas divisum and chronic pancreatitis is controversial. We report the cases of two patients aged 40 and 53 years suffering from recurrent pancreatitis and known to have histologically proven idiopathic chronic pancreatitis. One patient had insulin dependent diabetes. Pancreatography demonstrated in these two cases a pancreas divisum with a dilated dorsal pancreatic duct. A pancreatico-jejunostomy was performed, associated in one case with splenopancreatectomy for pseudo-cyst. With a follow-up of 32 and 78 months, both patients were free of symptoms and the diabetic patient had normal blood glucose levels with diet alone. The clinical history of the patients suggests a relationship between pancreas divisum and chronic pancreatitis and that pancreatico-jejunostomy may improve pancreatic pain and pancreatic function.


Enhanced Secretion of Beta-Defensins in Endometrial Tissues and Epithelial Cells by Soy Isoflavones.
This study aimed to investigate whether endometrial tissues and endometrial epithelial cells were capable of secreting beta-defensin (BD)-1 and -2, and soy isoflavones genistein or daidzein could promote these BD secretions. The effect of genistein on Cl- secretion in correlation with the BD secretion was also examined. Endometrial tissues or glandular epithelial cell monolayer were mounted in Ussing chamber for measurement of electrical parameters. The sample solutions from apical and basolateral compartments were collected before and after genistein or daidzein addition for the measurement of BD-1 and-2 levels by using ELISA technique. Endometrial tissues and epithelial cells constitutively secreted both BD-1 and -2 mostly at the apical compartment. Both genistein and daidzein induced BDs secretion which reached a peak at 5-15 min. The apical secretion of BDs was coincidence with increased Cl- secretion induced by genistein. Endometrial tissues and epithelial cells contributes to basal host defense against infection by secretion of BD-1 and -2, which could be enhanced by genistein or daidzein. This finding implies that these potent constituents of soy isoflavones may be useful to promote the innate immune function of human endometrium.


Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.
Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and vinblastine compared to Flp-In-293/Mock cells although the four guanidine alkaloids exhibited cytotoxicity against the two Flp-In-293 cells. Furthermore, the four guanidine alkaloids were also found to stimulate the ATPase activity of ABCB1 in ATPase assays. These results suggest that ABCB1 can confer the resistance to the cytotoxic guanidine alkaloids by transporting them.


Hand-foot-and-mouth disease: report of a case in Texas.
Coxsackie virus infections are highly contagious and can occur at epidemic levels within low socioeconomic populations. Since these diseases spread by contact, summer and fall occurrences increase significantly. A low grade fever and malaise are often related to non-specific viral infections. Hand-foot-and mouth disease (HFMD) is specifically caused by coxsackie virus.


Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis.
Divers breathe higher partial pressures of oxygen at depth than at the surface. The literature and diving community are divided on whether or not oxygen is narcotic. Conversely, hyperbaric oxygen may induce dose-dependent cerebral hyperexcitability. This study evaluated whether hyperbaric oxygen causes similar narcotic effects to nitrogen, and investigated oxygen's hyperexcitability effect. Twelve human participants breathed "normobaric" air and 100% oxygen, and "hyperbaric" 100% oxygen at 142 and 284 kPa, while psychometric performance, electroencephalography (EEG), and task load perception were measured. EEG was analyzed with functional connectivity and temporal complexity algorithms. The spatial functional connectivity, estimated using mutual information, was summarized with the global efficiency network measure. Temporal complexity was calculated with a "default-mode-network (DMN) complexity" algorithm. Hyperbaric oxygen-breathing caused no change in EEG global efficiency or in the psychometric test. However, oxygen caused a significant reduction of DMN complexity and a reduction in task load perception. Hyperbaric oxygen did not cause the same changes in EEG global efficiency seen with hyperbaric air, which likely related to a narcotic effect of nitrogen. Hyperbaric oxygen seemed to disturb the time evolution of EEG patterns that could be taken as evidence of early oxygen-induced cortical hyperexcitability. These findings suggest that hyperbaric oxygen is not narcotic and will help inform divers' decisions on suitable gas mixtures.


Affinity modulation in platelet alpha 2 beta 1 following ligand binding.
In order to test for ligand-induced change in the affinity of platelet alpha 2 beta 1 to collagen we passaged labeled viable platelets through a column of fibrillar collagen and used stringent lysis conditions to remove all low-affinity receptors. A high affinity fraction left on the collagen could be eluted with DTT and 2% SDS. Antibodies raised against it Western-blotted alpha 2 beta 1. Functional tests performed with the antibodies confirmed the involvement of the high affinity proteins in platelet-collagen interactions attributed to alpha 2 beta 1: inhibition of collagen-specific platelet adhesion and aggregation. EDTA, chaotropic agents or low pH did not elute the high affinity fraction of alpha 2 beta 1. However, DTT followed by acetic acid did. Our data suggest that 1) ligand binding induces the formation of a new disulfide bond in a fraction of alpha 2 beta 1, 2) that this bond is intrareceptor and 3) that this change increases the affinity of the receptor to its ligand.


[Role of inflammation mediators in the pathogenesis of heart failure].
A number of factors are involved in congestive heart failure pathogenesis. Among these, inflammatory mediators could have a crucial role. Patients with congestive heart failure show increased plasma levels of "proinflammatory cytokines", in particular tumor necrosis factor-alpha and interleukin-6. Clinical and experimental models have demonstrated that these cytokines induce left ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the possibility that increased plasma concentration of cytokines could not be just an epiphenomenon, but an effective pathogenetic mechanism of disease progression. Additional inflammatory proteins involved in the acute phase response could play a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long pentraxin, structurally related, although with different functions, to C-reactive protein, is produced by immune system cells, fibroblasts and particularly by cardiac endothelial cells and myocytes, as demonstrated in murine and human models. Its synthesis is rapidly induced after exposition to bacterial lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the acute local inflammatory response to myocardial injury (e.g. necrosis) and in heart failure pathogenetic mechanisms, but its exact role is not yet settled. Defining the specific part played by these molecules in the pathogenesis of heart failure could lead to new therapeutic approaches in the treatment of cardiac insufficiency.


Ground states, excited states, and metal-ligand bonding in rare earth hexachloro complexes: a DFT-based ligand field study.
Metal (4f)-ligand (Cl 3p) bonding in LnCl(6)(3-) (Ln = Ce to Yb) complexes has been studied on the basis of 4f-->4f and Cl,3p-->4f charge-transfer spectra and on the analysis of these spectra within the valence bond configuration interaction model to show that mixing of Cl 3p into the Ln 4f ligand field orbitals does not exceed 1%. Contrary to this, Kohn-Sham formalism of density functional theory using currently available approximations to the exchange-correlation functional tends to strongly overestimate 4f-3p covalency, yielding, for YbCl(6)(3-), a much larger mixing of Cl 3p-->4f charge transfer into the f(13) ionic ground-state wave function. Thus, ligand field density functional theory, which was recently developed and applied with success to complexes of 3d metals in our group, yields anomalously large ligand field splittings for Ln, the discrepancy with experiment increasing from left to the right of the Ln 4f series. It is shown that eliminating artificial ligand-to-metal charge transfer in Kohn-Sham calculations by a procedure described in this work leads to energies of 4f-4f transitions in good agreement with experiment. We recall an earlier concept of Ballhausen and Dahl which describes ligand field in terms of a pseudopotential and give a thorough analysis of the contributions to the ligand field from electrostatics (crystal field) and exchange (Pauli) repulsion. The close relation of the present results with those obtained using the first-principles based and electron density dependent effective embedding potential is pointed out along with implications for applications to other systems.


Cardiac connexins, mutations and arrhythmias.
Connexins are the pore forming subunits of gap junction channels. They are essential for cardiac action potential propagation. Connexins are modified at the transcriptional or posttranslational levels under pathological states such as cardiac hypertrophy or ischemia, thus contributing to the arrhythmogenic substrate. However, the relation between nucleotide substitutions in the connexin gene and the occurrence of cardiac arrhythmias remains largely unexplored. Recent studies have reported an association between nucleotide substitutions in the connexin40 (Cx40) and connexin43 (Cx43) genes (GJA5 and GJA1, respectively) and cardiac arrhythmias. Of note, however, germline mutations in Cx43 are considered causative of oculodentodigital dysplasia, a pleiotropic syndrome wherein cardiac manifestations are notoriously absent. Here, we review some of the current knowledge on the association between cardiac connexins and inherited arrhythmias.


Airborne remote sensing of tropospheric water vapor with a near-infrared differential absorption lidar system.
A near-infrared airborne differential absorption lidar (DIAL) system has become operational. Horizontal and vertical water vapor profiles of the troposphere during summer (nighttime) conditions extending from the top of the planetary boundary layer (PBL) up to near the tropopause are investigated. These measurements have been performed in Southern Bavaria, Germany. The system design, the frequency control units, and an estimation of the laser line profile of the narrow-band dye laser are discussed. Effective absorption cross sections in terms of altitude are calculated. Statistical and systematic errors of the water vapor measurements are evaluated as a function of altitude. The effect of a systematic range-dependent error caused by molecular absorption is investigated by comparing the DIAL data with in situ measurements. Typical horizontal resolutions range from 4 km in the lower troposphere to 11 km in the upper troposphere, with vertical resolutions varying from 0.3 to 1 km, respectively. The lower limit of the sensitivity of the water vapor mixing ratio is calculated to be 0.01 g/kg. The total errors of these measurements range between 8% and 25%. A sine-shaped wave structure with a wavelength of 14 km and an amplitude of 20% of its mean value, detected in the lower troposphere, indicates an atmospheric gravity wave field.