Simian hemorrhagic fever virus (SHFV) variant NIH LVR42-0/M6941 is the only remaining SHFV in culture, and only a single genome sequence record exists in GenBank/RefSeq. We compared the genomic sequence of NIH LVR42-0/M6941 acquired from the ATCC in 2011 to NIH LVR42-0/M6941 genomes sequenced directly from nonhuman primates experimentally infected in 1989. Arterivirus , causes viral hemorrhagic fever (VHF) in captive Asian macaques (reviewed in reference Macaca mulatta) inoculated with a whole blood suspension from a deceased SHFV-infected stump-tailed macaque (Macaca arctoides) (Simian hemorrhagic fever virus (SHFV), a member of the genus ctoides) . Resultsctoides) . Anotherctoides) .Chlorocebus aethiops; A095 and A230) and one rhesus monkey (I-618) on different days (d) postinoculation . Briefly, RNA was isolated with the omission of carrier RNA , and randomly primed double-stranded cDNA was synthesized , as previously described  by Vatter et al. . FurtherKM373784, KM371111, KM371105, KM371106, KM371107, KM371108, KM371109, and KM371110, respectively.The GenBank accession numbers of SHFV variant NIH LVR42-0/M6941 isolates KS_06_17_11, RJ_03_26_10, A095-d5, A095-d7, A230_d5, A230_d7, I618_d3, and I-618_d5 are


Migraine remains poorly treated with few effective preventive medications available.We evaluated the efficacy and safety of LY2951742, a fully humanized monoclonal antibody to Calcitonin Gene-Related Peptide (CGRP) for migraine prevention.Eligible subjects with 4-14 migraine headache days (MHD) per month were randomized in a double-blind manner to LY2951742 or placebo, administered subcutaneously, every other week over a 12-week period. The primary endpoint was the mean change from baseline in number of MHD in the last 28 day period (month three); secondary end points included the mean change in headache days, migraine attacks, and the 50% responder rate at month 3.Mean change in MHD (primary) was -4.2 vs. -3.0 for LY2951742 (n=107) and placebo (n=110), respectively (p = 0.003). LY2951742 was superior to placebo for all secondary endpoints including headache days -4.9 vs. -3.7 (p = 0.0117), migraine attacks -3.1 vs. -2.3 (p = 0.0051), and 50% responder rate, 70% vs. 45% . An exploratory endpoint of complete response (100% reduction in MHD in month 3) was 31.6% vs. 17.3%  for LY2951742 and placebo, respectively. Adverse events reported by approximately ≥5% of LY2951742-treated patients and more frequently with LY2951742 than placebo included upper respiratory tract infections, injection site pain, neck pain, abdominal pain, dizziness, injection site erythema, rash, hypertension and pain in extremity.Treatment with LY2951742 demonstrated significant separation from placebo on the primary and secondary endpoints. LY2951742 appeared to be safe and well-tolerated.


Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in HIV/TB co-infected patients. Data on ART outcome for HIV/TB co-infected patients managed in primary health care in low-income regions is limited. We compared virological suppression rates, mortality and retention in care in HIV-positive adults receiving care in five Ethiopian health centres with regard to TB co-infection.HIV-positive ART-naïve adults eligible for ART initiation were prospectively recruited from October 2011 until March 2013. At inclusion, all patients submitted sputum for microbiological TB testing . Virological suppression rates after six months of ART  with regard to TB status was the primary outcome. The impact of HIV/TB co-infection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models.Among 812 participants , 678 started ART during the follow-up period . Median CD4 cell counts at ART initiation were 161 cells/µL  and 184  for TB and non-TB patients, respectively (p=0.05). No difference in retention in care between TB and non-TB patients was observed during follow-up; 25 (3.7%) patients died and 17 (2.5%) were lost to follow-up . Overall rates of VS at six months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB co-infection (<40 copies/mL: 65/92 (70.7%) vs. 304/420 (72.4%), p=0.74; <400 copies/mL: 77/92 (83.7%) vs. 377/420 (89.8%), p=0.10, respectively). CD4 cell count increase during treatment was 87  and 103 cells/µL  for TB and non-TB patients, respectively, with no significant difference between the two groups (p=0.49).High rates of VS were achieved in adults receiving ART at Ethiopian health centres managed by non-physician clinicians, with no significant difference with regard to TB co-infection. These findings demonstrate the feasibility of combined ART and anti-TB treatment at primary health care level in low-income countries. This study is registered with clinicaltrial.gov, NCT01433796.


Long-term prognosis after coronary artery bypass grafting (CABG) is related to the patency of coronary grafts, and pathogenesis of graft closure is linked to platelet aggregation. We analyzed the effect on late outcomes of postoperative dual antiplatelet treatment (DAT), maintained during the first year, compared to single antiplatelet treatment (SAT).A) Primary: Evaluation of adverse cardiovascular events: Hospital admission for acute coronary syndromes (ACS), unplanned target-vessel revascularization (UTVR), stroke and death of cardiovascular origin. B) Secondary: Evaluation of safety: analysis of bleeding events (BE).Retrospective study including all CABG patients during the years 2009-2010, with two years of clinical follow-up. Patients were classified in: A) SAT: daily 100 mg ASA. B) DAT: daily 100 mg ASA plus daily 75 mg clopidogrel.The study included 452 patients: 287 SAT (63.5%); 165 DAT (36.5%). 11.9% suffered a primary end-point event; 6.6% ACS; 4.4% UTVR; 1.5% stroke; 3.8% died during follow-up. Safety: 2 (0.4%) suffered a major BE, and 10 (2.2%) minor BE.DAT was associated with a reduction of the primary end-point from 14.6% to 7.3% (p = 0.020). ACS were reduced from 8.7% to 3.0% (p = 0.020). There were no differences in UTVR nor stroke. Mortality during follow-up was lower in DAT .A multivariate Cox proportional-hazards regression was performed; DAT was independently associated with the reduction of events .The greatest benefit of DAT was seen after Off-pump CABG  and in diabetic patients .DAT is associated with a reduction of late adverse cardiovascular events after CABG, especially in Off-pump CABG and in diabetic patients. DAT did not increase the risk of BE.


Klebsiella pneumoniae strain IIEMP-3, isolated from Indonesian tempeh, is a vitamin B12-producing strain that exhibited a different genetic profile from pathogenic isolates. Here we report the draft genome sequence of strain IIEMP-3, which may provide insights on the nature of fermentation, nutrition, and immunological function of Indonesian tempeh. Klebsiella pneumoniae in Indonesian tempeh is intriguing since it produces vitamin B12 in tempeh   method showed that K. pneumoniae strain IIEMP-3 was determined employing a HiSeq 2000 platform  through a commercial service provider . A 350-bp paired-end library was constructed and sequenced, producing 10 million paired-end reads with read lengths of 100 bp.The nucleotide sequence of De novo assembly was processed using Velvet version 1.2.07 (n 1.2.07  with k-mn 1.2.07  resultedn 1.2.07  with 5 tn 1.2.07  with agghttp://www.ncbi.nlm.nih.gov/genome/annotation_prok). A total of 5,285 genes, 5,096 coding sequences (CDSs), 106 pseudogenes, 5 rRNAs, 77 tRNAs, and 1 noncoding RNA (ncRNAs) were identified.Genome annotation was performed employing the NCBI Prokaryotic Genome Annotation Pipeline (Klebsiella pneumoniae IIEMP-3 has been deposited in GenBank under the accession number LMAP00000000.The genome sequence of


A peer-reviewed Formal Comment by Prof. Backert and colleagues discussing results relating to this work has been published as Tegtmeyer N, Lind J, Schmid B, Backert S (2014) Helicobacter pylori CagL Y58/E59 Mutation Turns-Off Type IV Secretion-Dependent Delivery of CagA into Host Cells. PLOS ONE 9(6): e97782. doi:10.1371/journal.pone.0097782Following discussion among Associate Editor Matt Hodgkinson, the authors, and the handling editor Jun Sun, and in response to the issues raised in the Formal Comment, we are posting a correction to address: 1) confirmation of the strain mutations by PCR, sequencing, and RT-PCR; 2) clarification of the availability of the strains.The authors have provided DNA sequencing and RT-PCR data in supporting information files:cagL mutant (A), revertant, and amino acid replacement mutants (B).cagL mutant, revertant, and amino acid replacement mutants using PCR.H. pylori clinical strain Hp1033 wild type, cagL insertion mutant, revertant, and amino acid replacement mutants.cagL expression for Hp1033 wild type, cagL mutant and replacement mutants co-cultured with AGS cells at pH 7.4 for 1 hour.CagL antibody, and so they are not able to show protein expression.The authors have no Anti-H. pylori reported in the manuscript may be done following a formal request. This application is necessary to comply with the regulatory processes in the authors' institution and the customs/export regulations between Taiwan and other countries.Sharing of the strains/isolates of Table S1Primers used for sequencing and RT-PCR.Click here for additional data file.Figure S1cagL mutant (A), revertant, and amino acid replacement mutants (B).The diagram of construction of Click here for additional data file.Figure S2cagL mutant, revertant, and amino acid replacement mutants by using PCR. PCR Amplicons from wild type, revertants, and amino acid replacement mutants are 1.1kb (using primer cagL-5 & cagL-6) or 1.4kb (using primer cagIL-1 & cagL-6), from cagL insertion mutants are 2kb. (A) M: marker; w: Hp1033 wild type; lane1-16: Hp1033 cagL::cat. (B) lane1-12: 26695 cagL::cat; lane 13-23: J99 cagL::cat; lane 24: Hp1033 cagL-Y58/E59 revertant. (C) lane 25-29: Hp1033 cagL-Y58D/E59 amino acid replacement mutants; lane 30: Hp1033 cagL::cat ; lane 31: Hp1035 cagL::cat. (D) lane 32-35: Hp1033 cagL-Y58/E59K amino acid replacement mutants. (E) lane 36-39: Hp1033 cagL-Y58D/E59K amino acid replacement mutants ; lane 40: Hp1035 cagL-Y58D/E59K amino acid replacement mutants. Arrows indicate the clones selected in this study.Confirming Click here for additional data file.Figure S3H. pylori clinical strain Hp1033 wild type, cagL insertion mutant, revertant, and amino acid replacement mutants. Multiple Alignments were processed by MAFFT L-INS-1 (v6.850b) from EMBL-EBI website. The blue blocks indicate the region of chloramphenicol resistance gene. The yellow block indicates the position of amino acid 58 and 59 residues.The sequencing results of Click here for additional data file.Figure S4cagL mutant and replacement mutants co-cultured with AGS cells at pH 7.4 for 1 hour, cagL expression was examined by RT-PCR. There was no difference in CagL expressions among Hp1033 wild type, revertant, and amino acid replacement mutants. The 3rd lane indicated there was no RNA contamination.After Hp1033 wild type, Click here for additional data file.


The publisher apologizes for the error.The word “Alleviating” is misspelled in the title. The correct title is: Penehyclidine Hydrochloride Pretreatment Ameliorates Rhabdomyolysis-Induced AKI by Activating the Nrf2/HO-1 Pathway and Alleviating Endoplasmic Reticulum Stress in Rats. The correct citation is: Zhao W, Huang X, Zhang L, Yang X, Wang L, Chen Y, et al. (2016) Penehyclidine Hydrochloride Pretreatment Ameliorates Rhabdomyolysis-Induced AKI by Activating the Nrf2/HO-1 Pathway and Alleviating Endoplasmic Reticulum Stress in Rats. PLoS ONE 11(3): e0151158. doi:


A. baumannii, K. pneumonia and P. aeruginosa strains, isolated from critically ill patients in a Greek ICU.The emergence of multidrug-resistant (MDR) pathogens is a major cause of infection-related mortality among critically ill patients. The synergistic effect between commonly used antibiotics against difficult to treat nosocomial MDR Gram-negative strains, if present, could provide a viable option as an alternative therapy. The aim of this study was to investigate the potential of antibiotic synergy against MDR A. baumannii, 41 K. pneumoniae and 64 P. aeruginosa strains, isolated during the period 2010 to 2013. All strains were resistant to carbapenems and showed reduced susceptibility or resistance to tigecycline or colistin (MIC >2), in accordance with CLSI guidelines. We evaluated double-drug combinations of carbapenem (CRB)/colistin (COL), tigecycline (TG)/COL, rifampicin (RIF)/COL, CRB/ gentamicin (GEN), CRB/amikacin (AMK) for A. baumannii, TG/COL, CRB/COL, piperacillin-tazobactam (PIP/TAZ)/GEN, CRB/GEN for K. pneumoniae and AMK/(PIP/TAZ), AMK/aztreonam (AZT), AMK/cefepime (CEF), AMK/CRB and CRB/COL for P. aeruginosa strains. In order to perform synergy tests, the E-test methodology  was used. Synergy was defined as a fraction inhibitory concentration (FIC) index ≤0.5, additive effect 0.5 to 1, indifferent or antagonistic effect >2 (Lorian definition).We tested 59 A. baumannii strains, the synergy effect of CRB/ COL was 55.9%, RIF/COL 38.9%, CRB/GEN 22%, CRB/AMK 20.3% and TG/COL 16.9%, respectively. Against 41 K. pneumoniae strains, synergy rates were: CRB/COL 43.9%, CRB/GEN 31.7%, PIP/TAZ/GEN 29.2% and TG/COL 24.4% respectively. Against 64 P. aeruginosa strains, synergy rates were: AMK/PIP/TAZ 64.6%, AMK/AZT 64.6%, AMK/CEF 58.3%, CRB/ COL 52%, AMK/CRB 25%.Against 59 MDR A. baumannii and K. pneumoniae strains tested was CRB/COL. The next most effective combination was RIF/COL and CRB/GEN respectively. No competitive effect was observed for RIF/COL combination in all cases tested. The most effective combinations for P. aeruginosa strains were AMK plus PIP/TAZ or AZT or CEF. The next most effective combination was CRB/ COL. We recommend implementation of an antibiotic synergy test for MDR pathogens as a routine antimicrobial test in the hospitals' microbiology laboratories, especially for critically ill patients, since some combinations seem to excel. Further studies are needed for the correlation of these combinations with clinical efficacy.The most effective combination for both the


A 48-year-old female presented with intermittent high-grade fever, chills, and severe myalgia for 4 days. There was no lymphadenopathy or hepatosplenomegaly. Investigations revealed hemoglobin concentration of 142 g/L; leucocyte count of 3.5x109/L with 54% neutrophils, 40% lymphocytes, 1% eosinophils, and 5% monocytes; and thrombocytopenia (platelet count of 55x109/L). Peripheral smear revealed numerous plasmacytoid lymphocytes and occasional cells with eccentrically placed nucleipacked with multiple prominent cytoplasmic vacuoles, morphologically consistent with Mott cells . MeanwhiNonmalignant reactive peripheral blood plasmacytosis can occur in tumors, autoimmune conditions, and infections . Polyclo


Delftia tsuruhatensis MTQ3 is a plant growth-promoting rhizobacterium (PGPR) isolated from tobacco rhizosphere. Here, we report the draft genome sequence of D. tsuruhatensis MTQ3. Several functional genes related to antimicrobial activity and environment adaption have been found in the genome. This is the first genome sequence of D. tsuruhatensis related to PGPR. Delftia tsuruhatensis, the type species of Delftia, is considered a plant growth-promoting rhizobacterium (PGPR)  –3, an or (PGPR) –, 5, and  (PGPR) –, 7. D. tD. tsuruhatensis MTQ3. Genomic DNA was extracted and sequenced using the Illumina HiSeq 2500 platform. The whole shotgun sequencing produced 8,206,833 paired-end reads with an average insert size of 580 bp (over 780-fold coverage). Another mate-paired (MP) library containing 3- to 5-kb inserts was constructed, and 13,462,994 paired-end reads were produced. All these raw data were then filtered by Trimmomatic v 0.30  (http://www.ncbi.nlm.nih.gov/genome/annotation_prok/).Here, we report the draft genome sequence of c v 0.30 , and Gapc v 0.30 . Final aD. tsuruhatensis MTQ3 is phylogenetically related to D. tsuruhatensis 391 (98.34%) (GenBank accession no. JNWH00000000), D. acidovorans CCUG 274B (97.96%) (AGYX00000000), D. acidovorans SPH-1 (94.94%) (NC_010002), Delftia sp. 670 (94.30%) (JNWI00000000), D. acidovorans CCUG 15835 (92.70%) (AGYY00000000), and Delftia sp. Cs1-4 (91.37%) (NC_015563).The genome consists of 6.27 Mb, with a G+C content of 66.79%. A total of 5,005 coding sequences (CDS), 13 pseudogenes, 72 tRNA genes, 1 noncoding RNA (ncRNA), and 10 rRNA genes were identified. Average nucleotide identity (ANI) analysis  revealedD. tsuruhatensis MTQ3 were identified in the genome, such as the bacteriocin gene (AA671_02705), polyketide synthase (PKS) gene (AA671_12420), nonribosomal peptide synthetase (NRPS) gene (AA671_12430), balhimycin synthesis gene (AA671_12395), quinolinate synthesis gene (AA671_01765), and phenazine synthesis gene (AA671_00865). Some genes responsible for the processing and transport of antibiotics were identified in the genome, including antibiotic biosynthesis monooxygenase gene , macrolide transporter gene (AA671_00980), and antibiotic ABC transporter substrate-binding gene (AA671_25335).Many genes involved in the antimicrobial activity of D. tsuruhatensis MTQ3 possesses genes with likely relevance to rhizosphere competence and adaptation in polluted environments. Specifically, quercetin dioxygenase  is likely a plant microbe-signaling bacterium involved in degrading plant-produced antimicrobial root exudates (In addition, exudates , 14. Proexudates . Genes rD. tsuruhatensis MTQ3 has been deposited in DDBJ/ENA/GenBank under the accession number LCZH00000000. The version described in this paper is the first version, LCZH01000000.The whole-genome shotgun project of


Chondroitin sulfate proteoglycan 4 (CSPG4) is a membrane bound proteoglycan, composed of an N-linked 280kDa glycoprotein, and a single 450kDa chondroitin sulfate linked proteoglycan . CSPG4 e16 pediatric tumor lines were assessed for CSPG4 expression. CSPG4 was detected by flow cytometry in 69% of the cell lines assessed: osteosarcomas: 143b,HOS-MNNG,MG63; synovial sarcomas: SYO-I,HSSY-II, alveolar/embryonal rhabdomyosarcomas: Rh18c,Rh30/Rh36, medulloblastoma: DAOY, melanoma: Mel624,Mel1300. CSPG4 expression site density was estimated with BD PE Quantibrite beads by flow cytometry.Using two different single chain variable fragments (scFv) known to target CSPG4 (225.28 and TP41.2), two anti-CSPG4 second generation CAR constructs were synthesized by transient transfection of retroviral packaging lines. Both constructs have identical intracellular signaling components . Healthy donor T cells were transduced with viral supernatants, and assessed for CAR expression. Anti-tumor activity was measured by cytokine release and tumor specific lysis. Cell surface expression of the CSPG4-based CARs was detected by flow cytometry using conjugated Protein L to target the expressed scFv light chain. 225.28 and TP41.2 based CAR T cells induced 25% and 31% lysis of target pediatric tumor lines, respectively (E:T ratio of 20:1). On further investigation, TP41.2 based CAR T cells were able to specifically lyse CSPG+ cell lines 143b, Rh30, and Rh18c at 40%, 37%, and 16%, respectively (E:T ratio of 30:1). Additionally, the TP41.2 and 225.28 CAR T cells were assessed for Interferon gamma (IFNy) production by flow cytometry. Compared to mock T cells coincubated with varying tumor lines , the TP41.2 and 225.28 CAR+ T cells had significantly positive populations for IFNy production (p < 0.0001), predominantly in the CD8+ population.in vitro at significant levels (p = 0.01). Targeting CSPG4 with CAR redirected T cells represents a new strategy for eliminating these pediatric malignancies in an antigen specific, cell-mediated manner.High levels of CSPG4 are present on a variety of pediatric solid tumors. TP41.2 CSPG4-based CAR T cells target, generate significant levels of IFNy, and lyse osteosarcoma


Porphyromonas gingivalis is strongly associated with periodontitis. P. gingivalis strain trafficking and tissue homing differ widely, even among presumptive closely related strains, such as W83 and A7436. Here, we present the genome sequence of A7436 with a single contig of 2,367,029 bp and a G+C content of 48.33%. Porphyromonas gingivalis is an oral bacterium that is associated with periodontal disease  and grown as previously described (escribed . Genomicescribed  (Roche).https://www.ebi.ac.uk/~zerbino/velvet/) (http://www.phrap.org/consed/consed.html) (–http://metagenomics.anl.gov) (http://img.jgi.doe.gov/er) (https://geneprimp.jgi-psf.org) (GS-20 reads were assembled using Velvet version 0.7.63 (velvet/)  and Newbed.html) –24 and banl.gov)  and IMG-.gov/er) , then ampsf.org) .P. gingivalis A7436 has approximately 57-fold coverage and contains a single contig of 2,367,029 bp (G+C content of 48.33%). A total of 2,078 genes were annotated, which included 2,011 predicted coding sequences (CDSs), 53 tRNAs, 12 rRNAs, and 1 transfer-messenger (tmRNA). There are 234 subsystems in the genome. 169 protein metabolism, 164 cofactors, vitamins, prosthetic groups, and pigments, 74 RNA metabolism, 87 DNA metabolism, 96 carbohydrates, and 19 membrane transport subsystem features were observed.The genome of P. gingivalis A7436 genome was compared to P. gingivalis strains W83, ATCC 33277, and TDC60 using RAST (The annotated ing RAST  and IMG-ing RAST . All-to-ing RAST , 17. HowP. gingivalis strains.The availability of the A7436 genome expands our ability to compare observed behavior with genotype in a growing number of CP011995. The version described is the first version.This genome sequencing project was deposited in GenBank under accession no.


We also accessed the proliferative role and downstream targets of Pak1 in endometrial cancer. Pak1 was expressed in cytoplasm whereas Pak4 and p-Pak4 were expressed in both cytoplasm and nucleus of endometrial tissues. In normal endometrium, significantly higher Pak1 (P = 0.028) and cytoplasmic p-Pak2 (P = 0.048) expression was detected in proliferative endometrium than secretory endometrium. Pak1, cytoplasmic and nuclear Pak4 and nuclear p-Pak4 was significantly overexpressed in endometrial cancer when compared to atrophic endometrium . Moreover, type I endometrioid carcinomas showed significantly higher Pak1 expression than type II non-endometrioid carcinomas (P<0.001). On the other hand, Pak1, Pak4 and p-Pak4 expression negatively correlated with histological grade  while p-Pak2 and cytoplasmic Pak4 expression inversely correlated with myometrial invasion . Furthermore, patients with endometrial cancers with lower cytoplasmic Pak4 expression showed poorer survival (P = 0.026). Multivariate analysis showed cytoplasmic Pak4 is an independent prognostic factor. Functionally, knockdown of Pak1, but not Pak4, in endometrial cancer cell line led to reduced cell proliferation along with reduced cyclin D1, estrogen receptor (ERα) and progestogen receptor (PR) expression. Significant correlation between Pak1 and PR expression was also detected in clinical samples. Our findings suggest that Pak1 and cytoplasmic p-Pak2 may promote cell proliferation in normal endometrium during menstral cycle. Pak1, cytoplasmic and nuclear Pak4 and nuclear p-Pak4 are involved in the pathogenesis of endometrial cancer especially in postmenopausal women. Pak1 promote endometrial cancer cell proliferation, particular in type I endometrioid carcinoma. Cytoplasmic Pak4 can be potential prognostic marker in endometrial cancer.p21-activated kinases (Paks) are serine/threonine protein kinases involved in biological events linked to malignant tumor progression. In this study, expression of Pak1, p-Pak2 Ser Endometrial cancer is the most common gynecological malignancy worldwide  and its p21-activated serine/threonine kinases (Paks) are effectors for the small Rho GTPases Rac1 and Cdc42 that play important roles in a variety of cellular functions, including cell morphogenesis, motility, survival, anchorage-independent growth and angiogenesis, all of which are prerequisite steps for tumor formation and tumor invasion . Based oSer20 expression in ovarian cancer was also detected , and cleared by centrifugation at 4°C. Protein concentration was determined by DC (detergent compatible) protein assay . 20 μg protein was resolved by SDS-PAGE, transferred to polyvinylidene difluoride membrane, and hybridized with corresponding antibodies . Mann-Whitney test was applied for comparison between two groups. Kruskal-Wallis rank test was applied for comparison among multiple groups. Survival analysis was performed by Kaplan-Meier analysis and log-rank test. P = 0.001) and secretory (P = 0.004) endometrium, atypical hyperplasia (P = 0.042) and endometrial cancers (P = 0.044) (P<0.05) was observed  . Signifiobserved . Althougobserved . SimilarP<0.05) except complex hyperplasia whereas nuclear p-Pak2 only showed significantly higher expression in proliferative endometrium than atrophic (P = 0.046) and secretory (P = 0.028) endometrium and endometrial cancers (P = 0.007) (P = 0.007) and pure atypical hyperplasia (P = 0.013) showed significant higher cytoplasmic p-Pak2 expression  and pure atypical hyperplasia   . Althougpression . Furtherctively) .P<0.05) (P = 0.047) and endometrial cancers (P = 0.036) (P = 0.026)  (P<0.05)  . SignifiUp-regulation of Pak1 and Pak4 mRNA and protein expression was also found in cancer cell lines  compared with normal endometrial cells by qPCR  and WestP<0.05), but not with other clinical parameters (P<0.05) (P<0.05) (P<0.05)  and patients’ age at diagnosis  . There w(P<0.05) . Higher (P<0.05) . No signP = 0.026), but not Pak1, nuclear and cytoplasmic p-Pak2, nuclear Pak4, nuclear and cytoplasmic p-Pak4, resulted in a poorer survival in endometrial cancer patients .Kaplan-Meier-survival analyses revealed that lower expression of cytoplasmic Pak4 Click here for additional data file.S2 Table(DOC)Click here for additional data file.S3 Table(DOC)Click here for additional data file.


Postoperative morbidity after sleeve gastrectomy is decreasing, but remains significant. Bleeding and surgical fistules remain the leading causes of morbidity and mortality. In several studies in postoperative care of obese patients, non-invasive positive pressure ventilation (NPPV) reduced the risk of lower respiratory tract infection and pneumonia , thereby2 above 90%. After period: standard treatment plus NPPV - all patients were submitted to a systematic postoperative protocol: NPPV was provided using an oxygen CIPAP system with 5 cmH2O. Statistical analysis: complication rates were compared using the chi-square test. P < 0.05 was considered statistically significant.A 4-year before-after study was conducted in a 19-bed intermediate care unit of a private hospital. Before period: standard treatment - all patients received oxygen supplementation to achieve SaOP <5%.A total of 857 patients were included. Inclusion characteristics were similar in the two groups: Before group - noNPPV: 352 patients, 2010 to 2011. Age: 40.58 ± 10.94, BMI: 42.79 ± 5.51, sex ratio F/M: 0.81. After group - NPPV: 504 patients, 2012 to 2013. Age: 40.81 ± 11.24, BMI: 42.92 ± 5.09, sex ratio F/M: 0.77. There is a significant between-group difference in the complication rate: Before group - noNPPV: 10 surgical fistula (2.84%) and six postoperative bleeding (1.70%); After group - NPPV: seven surgical fistula (1.39%) and three postoperative bleeding (0.6%). The overall complication rate fell from 4.54% to 1.98%. The chi-square statistic = 4.58. The number of degrees of freedom is 1. The value returned from the chi-square statistic is Systematic use of NPPV significantly improves morbidity in the postoperative care of sleeve gastrectomy.


Burkholderia sp. strain MP-1 was isolated from pesticide-contaminated soil. Herein, we report the draft genome sequence of strain MP-1, which contains 168 contigs of 8,611,053 bp, with a G+C content of 62.55% and 7,631 protein-coding genes. Burkholderia spp. are widely distributed in nature and include a large variety of related environmental, clinical, and agribiotechnological species (Burkholderia now comprises 78 species (http://www.bacterio.net/burkholderia.html). A methyl parathion (MP)-degrading bacterial strain, designated as Burkholderia sp. strain MP-1 (LMG 27927 = MCCC 1K00250), was isolated from the contaminated soil of a former pesticide-manufacturing company in Jiangsu province of China. The 16S rRNA sequence of the newly isolated strain showed the highest similarity to that of Burkholderia grimmiae DSM 25160T (98.45%)  of 8,611,053 bp (131-fold coverage), with an average G+C content of 62.55%. Automatic gene annotation was performed by the NCBI Prokaryotic Genomes Automatic Annotation Pipeline (PGAAP) (http://www.ncbi.nlm.nih.gov/genomes/static/Pipeline.html). The genome comprises 7,791 genes, including 55 tRNA genes for all 20 amino acids, 3 rRNA genes, 1 small noncoding RNA gene, 101 pseudogenes, and 7,631 protein-coding genes (CDS) (with an average length of 950 bp), which give a coding intensity of 84.2%. In all, 4,853 proteins were assigned to Clusters of Orthologous Groups (COG) families , with a MiSeq system using paired-end sequencing technology. A total of 3,758,646 pair reads and 9,573 clean single reads  were assembled using Newbler 2.6. The genome of Burkholderia strains were investigated, such as that of Burkholderia pyrrocinia CH-67, whose genome contains genes encoding enzymes for aromatic compound degradation .The draft genome sequence of strain MP-1 has been deposited at GenBank under the accession no.


Oncotarget. 2015; 6:15594-15609doi:10.18632/oncotarget.3709Present Figure 2: During the assembly of figure 2C, the same image was inadvertently used for both the non-transfected and empty vector control.Corrected Figure 2:


As the eighth leading cause of annual mortality in the USA, influenza A viruses are a major public health concern. In 20% of patients, severe influenza progresses to acute lung injury (ALI). However, pathophysiological mechanisms underlying ALI development are poorly defined. We reported that, unlike wild-type (WT) C57BL/6 controls, influenza A virus-infected mice that are heterozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (HETs) did not develop ALI. This effect was associated with higher IL-6 and alveolar macrophages (AMs) at 6 days postinfection (d.p.i.) in HET bronchoalveolar lavage fluid (BALF). In the present study, we found that HET AMs were an important source of IL-6 at 6 d.p.i. Infection also induced TGF-β production by HET but not WT mice at 2 d.p.i. TGF-β neutralization at 2 d.p.i. (TGF-N) significantly reduced BALF IL-6 in HETs at 6 d.p.i. Neither TGF-N nor IL-6 neutralization at 4 d.p.i. (IL-6-N) altered postinfection weight loss or viral replication in either mouse strain. However, both treatments increased influenza A virus-induced hypoxemia, pulmonary edema, and lung dysfunction in HETs to WT levels at 6 d.p.i. TGF-N and IL-6-N did not affect BALF AM and neutrophil numbers but attenuated the CXCL-1/keratinocyte chemokine response in both strains and reduced IFN-γ production in WT mice. Finally, bone marrow transfer experiments showed that HET stromal and myeloid cells are both required for protection from ALI in HETs. These findings indicate that TGF-β-dependent production of IL-6 by AMs later in infection prevents ALI development in influenza A virus-infected HET mice. It has been estimated that seasonal influenza infections result in 12 influenza-related deaths per 100,000 persons per year in the United States, most of which occur in the elderly , which is associated with poor prognosis . Once AL+ absorption via epithelial Na+ channels (ENaC) and Cl− absorption or secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel  were intranasally infected with 10,000 plaque-forming units (pfu)/mouse of egg-grown influenza A/WSN/33 (H1N1) in 50 μl PBS with 0.1% BSA  wk old w. In our Thin sections (3 μm) were prepared from formalin-fixed, paraffin-embedded lung tissue . IL-6 wail-6 mRNA was determined by the ΔΔCt method and normalized to the endogenous control 18s rrna, which was not altered by infection  at 2 d.p.i. by intraperitoneal (i.p.) injection . To neut137Cs irradiator (6/mouse) (in 0.5 ml PBS) were then transplanted by tail vein injection into recipient mice, which were placed on Baytril antibiotic water bottles for 2–3 wk peri-irradiation. This protocol resulted in no outward clinical signs.As in our previous studies, bone marrow-recipient mice were irradiated with 1,000 cGy given in two doses by a 2 saturation, heart rate, lung homogenate viral titers, lung wet:dry weight ratios, lung mechanics, and BALF inflammatory mediators were performed as in our previous studies . Gaussian data distribution was verified by the method of Kolmogorov and Smirnov. Differences between group means were analyzed by one-way ANOVA, with Tukey-Kramer multiple-comparison posttests. il-6 gene expression in AMs isolated from HET mice than AMs from WT mice at 6 d.p.i. (We reported previously that attenuation of cardiopulmonary dysfunction in HETs infected with the A/WSN/33 H1N1) influenza strain  was associated with exaggerated AM and IL-6 responses at 6 d.p.i. N1 influeA. In con6 d.p.i. C.Given the known role of TGF-β as an anti-inflammatory cytokine  and an iTo determine whether the exaggerated IL-6 response to infection in HET mice was TGF-β dependent, influenza A virus-infected mice were treated with a single dose of a neutralizing antibody to TGF-β at 2 d.p.i. (TGF-N) . ControlTo determine whether altered TGF-β and IL-6 responses to infection contribute to protection from influenza A virus-induced ALI, we examined the effects of TGF-N and IL-6-N on weight loss, viral replication, and cardiopulmonary function in influenza A/WSN/33 virus-infected mice at 6 d.p.i. We selected this time point because it would allow us to directly compare the downstream effects of treatment with anti-TGF-β at 2 d.p.i. with those of treatment with anti-IL-6 at 4 d.p.i. Postinfection weight loss at 6 d.p.i. did not differ between untreated WT and HET mice A. IgG trIn the absence of treatment, lung water content (wet:dry weight) remained normal  in HET mice at 6 d.p.i. but was significantly elevated in WT controls . Both TGIn the absence of treatment or after treatment with IgG, static and dynamic lung compliance were both significantly higher  in infected HETs at 6 d.p.i. B. ProtecAs in our earlier studies, BALF from influenza A/WSN/33 virus-infected HET mice contained far greater numbers of AMs than WT controls at 6 d.p.i. A. HoweveWe previously reported that BALF IFN-γ, IL-10, CC chemokine ligand 2 (CCL-2)/monocyte chemotactic protein 1 (MCP-1), CCL-5/RANTES, and CXCL-10/inducible protein 10 content did not differ between WT and HET mice at 6 d.p.i. . However, both treatments significantly reduced BALF CXCL-1/KC content in both mouse strains. In WT mice, both TGF-N and IL-6-N also significantly reduced BALF IFN-γ but increased IL-12 at 6 d.p.i. TGF-N, but not IL-6-N, also reduced BALF CCL-5/RANTES in WT mice at this time point. In contrast, neither treatment impacted BALF IFN-γ or CCL-5/RANTES in HET mice, and only IL-6-N significantly increased BALF IL-12 at 6 d.p.i. Treatment with nonspecific IgG had no effect on CXCL-1/KC, IFN-γ, IL-12, or CCL-5/RANTES in either mouse strain.We previously demonstrated that HET AMs were necessary for protection from influenza A virus-induced ALI in HET mice . To deteDespite a 50% reduction in cell-surface CFTR expression and anion transport , we and Previous investigators have reported that an attenuated AM response contributes to increased influenza severity , 59, 64.We found no differences in viral replication kinetics and BALF neutrophil counts between WT mice, untreated or IgG-treated HETs, and antibody-treated HETs at 6 d.p.i. This indicates that, in our model, influenza-induced ALI is independent of these factors. Moreover, we did not find that development of ALI in HETs following TGF-N and IL-6-N was associated with development of a so-called “cytokine storm” , 33, 62.Some investigators have reported an association between high BALF IL-6 and increased influenza mortality , 39, 56.Greater influenza severity has also been linked to inadequate anti-inflammatory responses. TGF-β is a potent inflammatory regulator , and inc1-subtype adenosine receptors, which induces increased CFTR-mediated Cl− secretion . A. Amer was supported by a Cystic Fibrosis Foundation Research Grant and The Ohio State University Public Health Preparedness in Infectious Diseases Program. I. Davis was supported by The Ohio State University Public Health Preparedness in Infectious Diseases Program and The National Heart Lung and Blood Institute at the National Institutes of Health (R01-HL102469).P. Woods was supported by No conflicts of interest, financial or otherwise, are declared by the authors.Author contributions: P.S.W., M.F.T., and N.M.C. performed experiments; P.S.W., M.F.T., N.M.C., and I.C.D. analyzed data; P.S.W. and I.C.D. interpreted results of experiments; P.S.W. and I.C.D. prepared figures; A.O.A. and I.C.D. edited and revised manuscript; A.O.A. and I.C.D. approved final version of manuscript; I.C.D. conception and design of research; I.C.D. drafted manuscript.


This study was undertaken to determine virulence factors among clinical Enterococcus species by phenotypic and molecular methods.Enterococci are opportunistic pathogens causing severe urinary tract infections, surgical wound infections, bacteremia and bacterial endocarditis. Aggregation substance  was the predominant species obtained, followed by E. faecalis (73/157). 72/157(45.85%) strains were positive for hemolysin, 61/157(38.85%) gelatinase, 16/157(10.19%) strong and 66/157(42%) were moderate biofilm producers phenotypically. PCR results showed, 37/157(23.56%) cylA, 81(51.59%) gelE, 10(6.36%) hyl, 87(55.41%) asa1 and 78(49.68%) isolates were positive for esp genes. Only 25/72, 32/61, 6/16 and 7/16 isolates were phenotypically and genotypically positive for cylA +hemolysin, gelE +gelatinase, esp +biofilm and asa1 +biofilm, respectively. Interestingly, E. faecalis carried multiple virulent genes (>4 genes) when compared with E. faecium among our study isolates.asa1>gelE>esp were the predominant genes observed. Majority of E. faecalis isolates were strong and E. faecium were moderate biofilm producers.Hemolysin and gelatinase were the predominant virulence factors expressed phenotypically whereas,


Feature tracking strain (FTS) is a new technique to evaluate myocardial deformation from routinely acquired cardiac magnetic resonance (CMR) cine images, however, it has not been validated in single ventricle patients. The purpose of this study is to validate FTS against myocardial tagged harmonic phase (HARP) images, considered the reference standard in non-invasive deformation analysis.We retrospectively analyzed CMRs of 15 consecutive single ventricle Fontan patients  between HARP and FTS, Pearson r = 0.67, p = 0.006. Average GCS was -19 (95% CI -4.3 to -33.8) from HARP and -16.7 (95% CI -6.4 to -26.9) from FTS. FTS yielded lower values (bias -2.3) than HARP (Figure Feature tracking analysis has moderate agreement with grid-tagged HARP measurements of circumferential strain in Fontan patients, with a trend towards lower strain values via FTS. Further validation of FTS in a large sample is warranted.Dr Kevin K. Whitehead: NIH K23 Grant HL089647 from the National Heart, Lung and Blood Institute. Dr. Mark Fogel: NIH R01HL098252-01, "Understanding mechanisms of Fontan failure and key predictors for patient outcome."


The asymmetric unit consists of one-quarter of the molecule (S site symmetry 2) and the complete molecule has 2/m (Ch2) point symmetry with the C=C bond in an E conformation. The geometry of the title compound is compared to those of a chloro derivative and a mercury complex.The title compound, C DOI: 10.1107/S1600536814023319/hb7285Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S1600536814023319/hb7285Isup3.cmlSupporting information file. DOI: Click here for additional data file.10.1107/S1600536814023319/hb7285fig1.tif. DOI: The molecular structure of DTCDD with displacement ellipsoids drawn at the 30% probability level. Symmetry codes: (i) 1-x, y, z; (ii) x, 1-y, 1-z; (iii) 1-x, 1-y, 1-z.Click here for additional data file.10.1107/S1600536814023319/hb7285fig2.tif. DOI: The unit-cell packing in DTCDD viewed down the b-axis.1030564CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Hepatitis C virus (HCV) represents one of the persistent viral infections afflicting humankind, and a significant proportion of chronic HCV disease progresses over time through liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). One potential mechanism underlying the chronic disease is believed to be viral escape from immune surveillance via upregulation of inhibitory molecules on immune cells by HCV. We investigated the diverse expression of various inhibitory molecules in PBMCs of healthy non-HCV controls and chronically HCV infected patients.The expression of inhibitory molecules on PBMCs was investigated in chronic HCV infected patients relative to healthy non-HCV controls using standard immunological and molecular methods. The serum levels of indoleamine 2, 3 deoxygenase (IDO) and cyclooxygenase-2 (COX-2) were also investigated.p≤0.01), PD-1 (p≤0.01), FOXP-3 (p≤0.01), BLIMP-1 (p≤0.01), CD160 (p≤0.01), CTLA-4 (p≤0.01), TRAIL (p≤0.01), BTLA (p≤0.01) and LAG-3 (p≤0.01) with fold change of 1.3, 0.4, 14.6, 0.87, 6.6, 0.4, 14.7, 10.9 and 2.5 respectively in chronically HCV infected patients. The plasma IDO and COX-2 levels were significantly higher (p=0.001) in chronically HCV infected subjects relative to healthy control.The gene expression profile of chronically HCV infected patients was significantly different from control individuals. Our results showed upregulation of TIM-3 (The upregulation of inhibitory molecules on PBMCs in chronically HCV infected patients suggest the contribution of these molecules to immune cells impairment in HCV infection. Viral persistence and eventual progression following potential evasion of the host immune armory via viral impregnation of inhibitory immune biosignatures in HCV disease pathogenesis warrants further elucidation.


Recenortality . We repoWe assessed outcome for HO patients at CC (primary outcome) and hospital discharge, and at 6-month and 1-year follow- up. Single variable logistic regression analyses, adjusted by age, gender and haematological diagnosis, and multivariate analyses were performed to identify independent predictors of outcome using STATA.P < 0.001), number of organs supported , P/F ratio , inotropic requirement , and IMV status  influenced unit survival at single variable analyses. At multivariate analysis, the P/F ratio  and IMV status  independently predicted outcome.A total of 225 HO patients were admitted to CC. Median age was 59 (interquartile range (IQR) 46 to 66) years. The most common haematological diagnoses on admission were acute myeloid leukaemia in 57 (25.3%) cases, non-Hodgkin lymphoma in 54 (24%) cases and multiple myeloma in 42 (18.7%) patients. Median APACHE II score was 21 (IQR 17 to 26). A total of 164 patients (72.9%) had at least one organ supported. Unit and hospital mortality rates were 34.7% (78 patients) and 49.3% (111 patients), respectively. At 6-month and 1-year follow-up, mortality increased to 63.1% (142 patients) and 70.5% (153 patients), respectively. The APACHE II score (OR = 0.93, 95% CI = 0.89 to 0.97, Organ failures and need for organ support correlated with outcome. P/F ratio and need for IMV were independent predictors of mortality, in agreement with previously published data . The CC


The two symmetry-related iodide anions bridge two LiI cations, forming an inversion dimer in which the Li2I2 plane is nearly perpendicular to the imidazol-2-ylidene ring, with a dihedral angle of 85.5 (3)°. No hydrogen bonding is observed in the crystal.In the title binuclear complex, [Li DOI: 10.1107/S2056989015009822/xu5851Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989015009822/xu5851fig1.tif. DOI: The molecular structure of the title compound with the atom-numbering scheme and 30% probability displacement ellipsoids.Click here for additional data file.10.1107/S2056989015009822/xu5851fig2.tifa . DOI: a axis.The packing diagram viewed along the 1402139CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


The increasing prevalence of ESBL-E in the community is a cause of concern for hospitals. Early detection of ESBL-E carriers on admission could allow timely implementation of control measures or appropriate selection of antimicrobials.To describe the current prevalence of ESBL-E rates upon admission to 4 different services at HUG, in the context of a multicenter European study (R-Gnosis).Patients admitted to 4 different services were screened by rectal swabs on admission. From January 2014 through January 2015, patients admitted to 4 wards, including: Ortho1 (sport traumatology), Ortho 2 (septic); Geriatrics (2 wards) and patients undergoing elective colorectal surgery (ECS) were screened from April 2013-October 2014.E. coli ; K. pneumoniae  and other Enterobacteriaceae . Among K. pneumonia carriers on admission, 24/26 (92.3%), had a previous hospitalization less than 12 months before admission screening and 21/26 (80.8%) had the previous hospitalization within 3 months only. ESBL-E carriage was 83/981 (8.4%) and 61/430 (14.2%) for Ortho 1 and 2 respectively; Geriatrics, 42/371 (11.3%); and ECS, 41/354 (11.6%).Overall, from 2394 admitted patients, 2136 were screened on admission (89.2%). Median age was 67.3 years (SD±20.9); 51.6% were male. Only 92/2136 (4.3%) had a previously known status of ESBL carriage. A total of 226/2136 (10.6%) patients were found to be ESBL-E carriers: E. coli. Patients admitted to septic orthopedics, geriatrics and ECS had a higher prevalence on admission. The majority of ESBL- Klebsiella pneumonia carriers had a recent history of hospitalization.Overall 10.6% of patients screened were ESBL-E carriers upon admission at HUG, mostly due to ESBL-producing None declared.


Pediatric chronic nonbacterial osteomyelitis (CNO) is a sterile inflammatory bone disorder in which innate and adaptive immunity dysfunction involved. Unifocal and multifocal disease courses are known. The modern treatment modalities include non-steroid anti-inflammatory drugs (NSAIDs), steroids, sulfasalazine (SSZ), methotrexate (MTX), bisphosphonates and biologic drugs - TNFα and IL1β-antagonists, with limited data.The aim of our study was to assess children with CNO and to evaluate efficacy of treatment modalities.Our cohort of CNO patients included 22 children, 8 boys and 14 girls. Monofocal disease course was in 9/22 children (40.9), multifocal in 13/22 (59.1) with mean 6 foci per patient. Histological confirmation was made in 13/22. Repeated MRI, CT and bone scintigraphy was performed in all patients. 3 patients have family history of autoimmunity  had comorbid autoimmune diseases (different types of JIA): 5 had monoarthritis, 1 arthritis with uveitis, 1 - psoriatic arthritis, 1 - polyarthritis PF neg, 6 had enthesitis-related arthritis (3 had ankylosing spondyloarthritis) and 1 had Crohn's disease. Spine involvement was in 5/22 (22.7). Onset age was 8.5  years, the right diagnosis delay was 3.6  months.Fever at onset, high painVAS and parental VAS scores highly correlated with risk of relapse disease course. Treatment: effectiveness of NSAID only 3/10 (30%), SSZ - 1/5 (20%), corticosteroids - 0/3 (short-term effect only), MTX - 4/7 (57.1%), pamidronate (PAM) with partial response 2/12 (16.7%) and with complete response - 10/12 (83.3%). Biologics - adalimumab and etanercept were effective in 3/4 (75%) patients, who fail to NSAID, MTX, PAM and SSZ. During disease course treatment lead to decreasing sings of disease activity, such as: parental VAS (p = 0.015), pain VAS (p = 0.026), MDVAS (p = 0.026), CRP (p = 0.0008), WBC (p = 0.006), ESR (p = 0.00024), PLT (0.014). The main effectiveness belonged to PAM (p = 0.003) and biologics (p = 0.07) in decreasing of pain VAS (-100% and -80%), parental VAS (-92% and -74%) and MD VAS . We calculated the cumulative probability of survival (event of interest: CNO flare) in the entire patient sample, depending the kind of treatment  obtained by the Kaplan-Meier method. Significant difference was proved comparing 3 therapeutical branches (p = 0.028). MTX treatment was effective (p = 0.04), as well as PAM (p = 0.01) than NSAID. Only flu-like syndrome during PAM treatment was in 10/12 (83.3%). No any others side effects were reported. All patients who had flu-like syndrome on first infusion had complete response to PAM, vice verse patients, who had no such complication had only partial response to this treatment.CNO is a group of chronic inflammatory conditions associated with different rheumatic diseases. The most effective treatment modalities were PAM, biologics and MTX. PAM was safety and can reach the rapid response and maintain long sustained remission.None declared.


Nevirapine (NVP) induces cytochrome P450 3A4 by which rilpivirine (RPV) is metabolized. Switching NVP to RPV could result in decreased RPV exposure with subsequent virological failure and dyslipidemia because NVP is regarded as the least dyslipidemic, non-nucleoside, reverse transcriptase inhibitor. This trial evaluated the efficacy, pharmacokinetics, safety and cardiovascular risks of switching NVP to RPV.Prospective open label controlled trial. HIV-1 patients with HIV-1 RNA <50 copies/mL on once daily NVP, emtricitabine/tenofovir (FTC/TDF) switched to single tablet RPV/FTC/TDF. Eligible patients on NVP, FTC/TDF were controls. Primary endpoint was week 12 HIV-1 RNA <50 copies/mL by intention to treat analysis. Secondary endpoints were week 24 HIV-1 RNA <50 copies/mL, NVP and RPV pharmacokinetics, safety and fasting lipids, Framingham risk scores (FRS) and Adult Treatment Panel III (ATP-III) lipid goals.Of 189 eligible patients, we included 50 RPV switchers and 139 NVP controls. Week 12 HIV-RNA was <50 copies/mL in 46/50 switchers (92.0%) which was not different from the hypothesized 90% week 12 suppression rate (p=.431). Forty-four of 50 switchers had week 24 HIV-1 RNA <50 copies/mL compared to 126/139 controls . NVP plasma concentrations were below detection level in all at week 3. Mean week 1 RPV trough concentration was 0.083 mg/L and comparable to phase III trial data (p=0.747). Adverse events occurred in 36 switchers, the majority (82.0%) were grade one. Two switchers discontinued RPV for side effects. Significant changes over 24 weeks (p<0.001) were observed in switchers on total cholesterol , low density lipoprotein (LDL)-C  and high density lipoprotein (HDL)-C . The TC/HDL-C ratio increased 0.20  and systolic blood pressure decreased 6.0 mmHg . The median FRS did not change over 24 weeks . More patients achieved LDL-C  and TC  ATP-III treatment goals at week 24 on RPV.A NVP to RPV switch does not influence RPV exposure and results in adequate ongoing HIV-1 suppression. RPV could be an option for patients at risk for cardiovascular diseases.


Mesorhizobium ciceri strain CC1192, an efficient nitrogen-fixing microsymbiont of Cicer arietinum (chickpea). The genome consists of 6.94 Mb distributed between a single chromosome (6.29 Mb) and a plasmid (0.65 Mb).We report the complete genome sequence of  Cicer arietinum (chickpea), a globally important grain legume, forms a N2-fixing symbiosis with soil bacteria (rhizobia) in the genus Mesorhizobium   , 7. Thushttp://www.dpi.nsw.gov.au/content/agriculture/resources/soils/australian-inoculants-research-group) and confirmed to fix N2 effectively with C. arietinum, using established methods (http://www.bioinformatics.babraham.ac.uk/projects/fastqc), and adaptors were removed by comparison against a comprehensive in-house adaptor sequence library. PacBio subreads were assessed using in-house software, and reads were automatically error-corrected in the assembly process.Strain CC1192 was sourced from the Australian inoculant industry mother culture ( methods . CC1192  methods . Whole-gde novo using the hybrid approach of SPAdes assembler version 3.6.2 (http://www.ncbi.nlm.nih.gov/genomes/static/Pipeline.html). The genome consists of 6,943,628 bp with an average GC content of 62.49%. There are 6,642 coding sequences distributed between a single circular chromosome of 6,295,397 bp and a single plasmid of 648,231 bp.The filtered Illumina and PacBio reads were assembled on 3.6.2 , with thon 3.6.2 . The asson 3.6.2  and annoM. loti R7A (nif and fix) appear to be located on a 419-kb symbiosis island integrated within the chromosome of CC1192 . This region also harbors a type IV secretion system, conjugative relaxase, biotin and nicotinate biosynthetic clusters, proteins known to control excision and transfer of ICEMlSymR7A  and CP015063 (plasmid pMc1192).The nucleotide sequence of the complete genome of CC1192 has been deposited in GenBank under the accession numbers


E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti-tumor activity.CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with  Clostridium  (E. coli (lux) and E. coli (lux/βG) in tumors reached a plateau from days 3 to 7  or E. coli (lux/βG) displayed splenomegaly (E. coli induced an immune response. This immune response may cause the transient body weight loss (9.2%) on day 3 observed after systematic administration of E. coli (The time course of lux/βG)] . The lums 3 to 7 , demonst tissues . Determiectively . Mice innomegaly , suggest E. coli .E. coli and beta-glucuronidase in tumor sections from E. coli (lux/βG), E. coli (lux), or PBS-treated mice. DAPI (blue) stained DNA in both live tumor cells and E. coli. DAPI-stained E. coli were observed as tiny spots that formed a dense cluster under UV excitation (E. coli further confirmed the location of the bacteria. Anti-E. coli beta-glucuronidase antibody staining showed that E. coli (lux/βG) but not E. coli (lux) expressed beta-glucuronidase in the tumor microenvironment. 72.4% ±13.9% of E. coli (lux) and 84.9% ± 9.2% of E. coli (lux/βG) were located in necrotic areas of tumors as distinguished by DAPI staining. E. coli (lux) and E. coli (lux/βG) didn’t show significant differences in localization to tumor necrotic areas  could enhance the anti-tumor activity of CPT-11, NOD/SCID mice bearing established HCT116 human colon tumors were i.v. injected with PBS or E. coli. Four days later, the mice were i.v. injected with 10 mg/kg CPT-11 or vehicle on two consecutive days. Treatment of mice with either CPT-11 or E. coli (lux/βG) alone significantly suppressed tumor growth as compared to treatment with vehicle alone (E. coli (lux/βG) produced significantly greater antitumor activity that either individual treatment. However, this effect did not depend on bacterial expression of beta-glucuronidase because treatment of mice with CPT-11 and E. coli (lux) suppressed tumor growth to a similar extent (E. coli (lux/βG) or E. coli (lux) produced significant but similar suppression of tumor growth (E. coli (lux/βG).To determine whether le alone . Combinar extent . Similarr growth , indicatE. coli (lux/βG) or E. coli (lux) could be caused by in vivo induction of endogenous beta-glucuronidase expression in E. coli (lux) or by in vivo loss of beta-glucuronidase expression in E. coli (lux/βG), we i.v. injected E. coli (lux/βG) or E. coli (lux) into mice bearing established HCT116 tumors and then i.v. injected a fluorescence glucuronide probe, FDGlcU, to measure in vivo beta-glucuronidase activity (E. coli (lux/βG) displayed similar luminescence emission but higher fluorescence emission than E. coli (lux) (E. coli (lux/βG) expressed significantly more beta-glucuronidase activity in tumors than did E. coli (lux). We conclude that E. coli (lux/βG) and E. coli (lux) displayed the expected high and low beta-glucuronidase activity in tumors.To investigate if the similar anticancer activity observed for treatment with CPT-11 and either activity . FDGlcU li (lux) , indicatE. coli therapy failure. To investigate differences between bacterial and adenoviral beta-glucuronidase therapy, we first compared the enzymatic activities of E. coli beta-glucuronidase (produced in E. coli (lux/βG) and murine beta-glucuronidase (produced by Ad/mβG). E. coli beta-glucuronidase hydrolyzed the glucuronidase substrate 4-Nitrophenyl β-D-glucopyranoside (pNPG) faster than did murine beta-glucuronidase at pH 7 [E. coli beta-glucuronidase displayed about 250 fold greater enzymatic activity for the hydrolysis of SN-38G compared to murine beta-glucuronidase at pH 7 (E. coli (lux/βG) or intratumoral injection of Ad/mβG. Again, the total beta-glucuronidase activity in tumors was significantly greater in mice treated with E. coli (lux/βG) than those treated with Ad/mβG (E. coli (lux/βG) can deliver more beta-glucuronidase activity to tumors as compared to direct injection of tumors with Ad/mβG.We previously showed that intratumoral injection of Ad/mβG, which allows expression of murine beta-glucuronidase as a membrane-anchored form on the surface of infected cells, can enhance the anti-tumor activity of CPT-11 . Therefo at pH 7 . Similar at pH 7 . Next, wh Ad/mβG . These rE. coli (lux/βG) or i.t. with Ad/mβG. Fluorescence signals were apparent in the tumors of mice receiving either treatment (E. coli (lux/βG)  (E. coli (lux/βG) produced more beta-glucuronidase activity in tumors, the beta-glucuronidase activity generated by Ad/mβG can more effectively hydrolyze a systemically administered glucuronide probe in the tumors.To assess the functional accessibility of beta-glucuronidase to systemically administered drugs, we i.v. injected the fluorescent glucuronide probe FDGlcU and then imaging the fluorescence intensity in tumors of mice treated i.v. with reatment , but mic(lux/βG) . A relatnce from  by the bnce from . Tumors (lux/βG) . We concE. coli (lux/βG) suggested that the chemical probe delivered via the tumor blood supply may not effectively contact beta-glucuronidase in the tumor. To test this idea, we compared the fluorescence in tumors after systemic (i.v.) or direct intratumoral (i.t.) injection of FDGlcU to mice previously treated with E. coli (lux/βG) or Ad/mβG. The dose of FDGlcU was decreased by 100 fold for intratumoral injection groups to prevent saturation of beta-glucuronidase in the tumors. While mice treated with Ad/mβG displayed similar fluorescence after either i.v. or i.t. injection of FDGlcU, the mice treated with E. coli (lux/βG) exhibited more tumor fluorescence after i.t. injection of FDGlcU (E. coli (lux/βG) was significantly greater when FDGlcU was directly injected into tumors as opposed to after i.v, administration  to allow tumor colonization and then directly injected a mixture of lysozyme/DNase I into tumors to break the bacteria cell wall. This approach was used to release beta-glucuronidase from the bacteria because the enzyme is too large (~280 kDa) to be efficiently secreted (results not shown). Mice were first i.v. injected with FDGlcU on day 4 to measure the fluorescence generated by hydrolysis of FDGlcU by intact bacteria in the tumors. After 48 h, the lysozyme/DNase I mixture was injected into tumors and then FDGlcU was again i.v. injected and tumor fluorescence was imaged. Imaging of bacterial luminescence showed the number of bacteria in tumors on days 4 and 6 were not significantly different  slow uptake of glucuronide compounds into E. coli may reduce the rate of prodrug hydrolysis and 2) the preferential accumulation of E. coli in necrotic regions of tumors may hamper efficient contact of systematically administered drugs with beta-glucuronidase. Our study suggests that both the cellular and spatial distribution of beta-glucuronidase, and possibly other therapeutic enzymes, might be an important barrier for effective bacteria-based prodrug cancer therapy.Methods to enhance the selectivity and efficacy of cancer chemotherapy are needed to improve patient outcome. Bacteria that have been modified to express enzymes for tumor-selective activation of proactive anticancer agents have been investigated as a promising approach to achieve more selective cancer therapy ,48. Heree CPT-11 ,35. Conve CPT-11 ,37. ThesE. coli was selected in our study to deliver beta-glucuronidase to tumors. There are two major advantages of using E. coli as a delivery vehicle for prodrug activation. First, E. coli can selectively colonize solid tumors, providing high tumor/normal tissue colonization ratios of around 10,000 fold [E. coli to mice. By contrast, Salmonella provides tumor/liver and tumor/spleen bacterial ratios of 100~1000 [E. coli for tumors may help reduce prodrug activation in normal tissues. Second, unlike liposomes, antibodies or replication deficient viruses, bacteria can proliferate in tumors [E. coli. These advantages have been recognized as indicated by the increasing number of papers investigating E. coli for tumor imaging and tumor therapy [E. coli used in our study (DH5α) does not express enterotoxins or lipopolysaccharides and is considered to be non-pathogenic [E. coli were also able to accumulate in murine tumors in immune-competent mice with similar toxicity as observed in immune deficient mice, suggesting that E. coli (DH5α) may be a suitable delivery vehicle for clinical applications.000 fold ,18,38. I100~1000 ,14. Like100~1000 –24. The n tumors –51. The  therapy ,20,38,52thogenic . We usedE. coli [E. coli. We constitutively expressed E. coli beta-glucuronidase in E. coli (lux/βG). These bacteria expressed about 60 ng beta-glucuronidase per 107 c.f.u. of bacteria and could convert cytotoxic concentrations of SN-38 from SN-38G. Because E. coli beta-glucuronidase can hydrolyze SN-38G to SN-38 about 250-fold faster than murine beta-glucuronidase  as compared to mice treated with Ad/mβG (E. coli beta-glucuronidase did not increase CPT-11 antitumor activity beyond that achievable by treating tumors with wild-type E. coli (E. coli (lux/βG)  .E. coli (lux/βG) therapy differ in several important facets as indicated in E. coli preferred to colonize the margins between necrotic regions and live cells (E. coli (lux/βG) with systemically-administered drugs. Second, the enzyme location in the cells differs. Ad/mβG was designed to express beta-glucuronidase on the cell membrane of infected cells whereas E. coli (lux/βG) expresses beta-glucuronidase in the periplasmic space of the bacteria. Glucuronide drugs can directly interact with membrane-anchored beta-glucuronidase but require receptor-mediated transport into E. coli to interact with beta-glucuronidase [E. coli (lux/βG) expresses E. coli beta-glucuronidase. The enzymatic activity of E. coli beta-glucuronidase is much greater than mouse beta-glucuronidase  as compared to Ad/mβG. First, beta-glucuronidase is expressed intracellularly in E. coli (lux/βG) but is present on the surface of cells as a membrane anchored form after infection with Ad/mβG. Thus, glucuronide substrates must enter bacteria, presumably via a glucuronide transporter complex present on E. coli [et al [E. coli preferentially accumulated at the border between viable cancer cells and necrotic regions  significantly increased probe hydrolysis (E. coli (lux/βG) in the tumor by intratumoral injection of lysozyme and DNase I to release beta-glucuronidase also significantly increased hydrolysis of the glucuronide probe (We identified two impediments that may account for the relatively poor performance of  E. coli , to cont E. coli . The seci [et al , we obse regions . Salmonef tumors , suggestf tumors –58 whichf tumors ,60. The drolysis , consistde probe . Taken tE. coli, other bacteria such as Salmonella and Shigella also prefer to colonize in the necrotic regions of tumors [Besides f tumors . Thus, df tumors –67 or inf tumors  might re


AbstractSymplanella Fennah, S. hainanensissp. n., S. recurvatasp. n. and S. zhongtuasp. n., are described and illustrated from South China. A checklist and a key to species of genus Symplanella are provided.Three new species of the Oriental caliscelid planthopper genus  PageBreakSymplanella was erected by Symplanella breviceps Fennah, 1987) and was placed in the subtribe Augilina of the tribe Ommatidiotini of the family Issidae. Recently, the genus was transferred to the family Caliscelidae by Caliscelidae. Symplanella from China and described one new species, Symplanella unipuncta Zhang & Wang, 2009, and proposed one new combination, Symplanella brevicephala  (transferred from Symplana Kirby). To date, only three species, Symplanella brevicephala (China: Yunnan), Symplanella breviceps (Burma: Dawna Hills) and Symplanella unipuncta (China: Hainan), are included in the genus Symplanella.The genus Symplanella are described and illustrated from South China . The generic characteristics are redefined. A checklist and a key to known species of Symplanella are provided.In this paper three new species of the genus Terminology follows Fennah, 1987http://species-id.net/wiki/SymplanellaSymplanella Fennah, 1987: 244; Symplanella breviceps Fennah, 1987, by original designation.PageBreaktriangular, venation as shown in Vertex , 15, 27 Oriental Region (China and Burma).Symplanella brevicephala ; China (Yunnan).Symplanella breviceps Fennah, 1987; Burma (Dawna Hills).Symplanella hainanensis sp. n.; China (Hainan).Symplanella recurvata sp. n.; China (Guangdong and Guangxi).Symplanella unipuncta Zhang & Wang, 2009; China (Hainan).Symplanella zhongtua sp. n.; China (Yunnan)http://zoobank.org/FA3249B6-4106-4928-9201-F444D3E76BEDhttp://species-id.net/wiki/Symplanella_recurvataBody length including forewing: male 5.78–5.98 mm (N = 6), female 6.15–6.25 mm (N = 12); forewing length: male 4.90–5.15 mm (N = 6), female 5.30–5.40 mm (N = 12).PageBreakPageBreaksegment. Central area of vertex and pronotum, base of mesonotum with somewhat pale yellowish red. Procoxae, mesocoxae, metapleura, abdominal sternites laterally and pregenital sternite of female fuscous.General color light yellowish brown with somewhat green. Ocelli reddish brown, eyes black brown. Antennae with one black spot at apex of second Vertex including eyes narrower than pronotum (0.86:1). Vertex shorter in middle line than broad at base (0.60:1). Frons 1.28 times longer in middle line than widest part. Pronotum slightly longer in middle line than vertex (1.21:1). Mesonotum 1.24 times as long as vertex and pronotum together in middle line. Forewing longer in middle line than broad at widest part (4.71:1). Hindwing longer in middle line than broad at widest part (2.01:1), venation as shown in Anal segment of male in posterior view  nearly l23°08'N, 113°14'E), on bamboo , 22 Nov. 2006, X.-S. Chen; paratypes: 5 ♂♂, 11 ♀♀, data same as holotype; 1 ♀, Guangxi, Daxin, Encheng, 4 May 2009, H.-R. Li.Holotype: ♂, China: Guangdong, Guangzhou, Huanan Botanical Garden .Bamboo (South China (Guangdong and Guangxi) .Symplanella unipuncta Zhang & Wang, 2009 but differs in: i) anal segment in lateral view with one stout process at apical margin ventrally, which curves cephalad apically ; ii) posterior margin of pygofer without process (with one process in Symplanella unipuncta); iii) aedeagus without process at base .This new species is closely related to The new species is named after the strongly recurved tip of the anal tube.http://zoobank.org/C12B4D8F-BF4B-4939-977B-D13F7CEDDF9Fhttp://species-id.net/wiki/Symplanella_hainanensisBody length including forewing: male 5.45–5.62 mm (N = 2), female 6.00–6.30 mm (N = 8); forewing length: male 4.40 mm (N = 2), female 4.65–4.95 mm (N = 8).PageBreakPageBreakGeneral color dirty yellowish brown. Ocelli reddish brown, eyes black brown. Antennae with one black spot at apex of second segment. Frons and clypeus mostly dark brown. Central area of vertex and pronotum, base of mesonotum with somewhat pale yellowish red. Procoxae, mesocoxae, metapleura, abdominal sternites laterally and pregenital sternite of female, fuscous.Vertex including eyes as wide as pronotum. Vertex longer in middle line than broad at base (1.24:1). Frons 1.67 times longer in middle line than widest part. Pronotum shorter in middle line than vertex (0.74:1). Mesonotum 0.87 times as long as vertex and pronotum together in middle line. Forewing longer in middle line than broad at widest part (4.00:1).Anal segment of male in dorsal view  with med18°47'N, 109°52'E), on bamboo, 9–12 Apr. 2009, X.-H. Hou; paratypes: 1 ♂, 8 ♀♀, data same as holotype.Holotype: ♂, China: Hainan, Diaoluoshan National Natural Reserve (Bamboo.South China (Hainan) .Symplanella breviceps Fennah, 1987, but can be distinguished from the latter in: i) frons mostly dark brown (stramineous in Symplanella breviceps); ii) vertex with anterior margin rounded (angulated in Symplanella breviceps); iii) posterior margin of pygofer with one spinous process dorsally (absent in Symplanella breviceps); iv) genital style in posterior view broad and short (narrow and long in Symplanella breviceps).This new species is similar to the type species from Burma, The new species is named after the type locality, Hainan Province, China.http://zoobank.org/B8FADA9C-2202-4485-928A-E17811BB1A59http://species-id.net/wiki/Symplanella_zhongtuaBody length including forewing: male 6.10–6.35 mm (N = 4), female 6.30–6.50 mm (N = 2); forewing length: male 5.15–5.30 mm (N = 4), female 5.20–5.40 mm (N = 2).PageBreakPageBreakGeneral color dirty yellowish brown. Ocelli reddish brown, eyes black brown. Antennae with one black spot at apex of second segment. Frons and clypeus mostly blackish brown. Central area of vertex and pronotum, base of mesonotum with somewhat pale yellowish red. Procoxae, mesocoxae, metapleura, abdominal sternites laterally and pregenital sternite of female fuscous.Vertex including eyes narrower than pronotum (0.98:1). Vertex shorter in middle line than broad at base (0.65:1). Frons 1.41 times longer in middle line than widest part. Pronotum as long in middle line as vertex. Mesonotum 1.45 times as long as vertex and pronotum together in middle line. Forewing longer in middle line than broad at widest part (4.45:1).PageBreakapical third abruptly narrowed, stick-like, apical margin rounded, each side with one spine-like process; phallobase lobe-like, each with one small spine at apex; aedeagus in lateral view , on bamboo, 28 July 2011, W.-B. Zheng and Z.-M. Chang; paratypes: 3 ♂♂, 2 ♀♀, data same as holotype.Holotype: ♂, China: Yunnan, Xishuangbanna, Menglun (Bamboo.Southwest China (Yunnan) .Symplanella brevicephala , but can be distinguished by: i) frons and clypeus mostly black ; ii) posterior margin of male pygofer having one stout spinous process at middle, directed ventro-caudad ; iii) genital style in lateral view dorso-apical angle broadly rounded ; iv) aedeagal shaft mostly straight .This new species is similar to The name is derived from transliteration of the Chinese “zhongtu”, meaning posterior margin of male pygofer having one stout spinous process at middle.Diversity of bamboo-feeding planthoppers. The current authors paid particular attention to the species of bamboo planthopper in field research and collected large quantities of specimens in the past twelve years. A number of new taxa or new records were found and some of them have been published (Bambusoideae (Delphacidae (78 species in 15 genera), Caliscelidae (three species in two genera), Cixiidae (two species in one genus) and Tropiduchidae (one species in one genus). The genus Symplanella with three known species and three new species described in this paper, represents the second bamboo-feeding genus in the tribe Augilini after Pseudosymplanella Che, Zhang & Webb, 2009  and the International Science and Technology Cooperation Program of Guizhou (No. 20107005).


A 10-year-old girl developed an enlargement of parotid and submandibular salivary glands and lymph nodes up to 2.5 cm associated with edema of her upper eyelids. In further follow-up, she developed non-palpable, vasculitic skin lesions. She received cephixime, that co-incided with partial regression of lymph nodes. Re-occurrence of vasculitic lesions with bilateral edema of upper eyelids resembling Miculitz disease was observed. At 7 years of age, she developed asthma requiring the use of bronchodilators. Clinical examination: a 10-year-old girl, pale skin, at the both calves irregularly shaped, livid, painless, vasculitic lesions, 2-3 cm in size. The upper eyelids are swollen. Parotid and submandibular salivary glands and submandibular lymph nodes are enlarged.To present clinical and laboratory investigations in IgG4-related disease in childhood.Routine laboratory tests including serum Ig concentrations, autoantibody screen, and histopathologic examination.Serum proteins were 101 g/l, albumins,38 g/l. Serum immunoglobulin IgA 1.92, IgM 0.38, IgG 42.2 g/l; IgG subclasses: IgG1 18.9 g/l (4.32-10.2), IgG2 17.05 g/l (0.72-4.3), IgG3 6.35 g/l (0.13-0.85), IgG4 9.02 g/l (0.02-0.93). Serum IgE 900 IU/ml . Coombs test negative. Autoantibody screening was negative. Serologic tests to HSV, EBV, CMV, hepatitis B and C, HIV were negative. Serum ACE was normal, 57 U/l. Neck ultrasound showed an enlargement of both parotid glands, lymph nodes and submandibular salivary glands up to 2.5 cm.Histopathathologic evaluation of lymph nodes, submandibular and parotid gland: the enclosed lymph node profiles show retained architecture with prominent reactive follicular hyperplasia. The intervening paracortex focally appears prominently hypovascular and contains a polymorphous lymphoid infiltrate comprising small lymphocytes, scattered immunoblasts, some plasma cells and focally prominent eosinophils.The salivary gland tissue shows abundant mononuclear inflammatory infiltrate with focal prominence of plasma cells and significant patchy sclerosis. The immunostainings including CD3, CD20 and CD79a show retained lymph node architecture. There is a reactive pattern of expression of Ki67, CDI0, bcl-2, bCl-G, CD21 and CD23. The immunostains also highlight fragmentation of some of the germinal centres. Most of the IgG staining plasma cells were of IgG4 positive phenotype.Bilateral, symmetrical, painless swelling of their lacrimal and salivary (parotid and submandibular) glands should raise suspicion on IgG4-related disease in childhood.None declared.


After an acute myocardial infarction with ST-segment elevation (STEMI) treated with percutaneous coronary intervention (PCI), the left ventricle (LV) can undergo negative remodeling (R-). We aimed to investigate whether global longitudinal strain (SGL) of the left ventricle (LV) predicts remodeling.Transthoracic echocardiography with speckle tracking imaging (TTE-STI) was performed 2 to 3 days after primary PCI and 6 months later in patients with diagnosis of STEMI. LV R- criteria were: LVEF increase ≤5% and end-diastolic volume increase ≥15%. Logistic regression and ROC curve analysis was used for the statistical analysis.n = 35, 42%) and no LV R- patients . Diabetes mellitus  and TnI levels  showed higher incidence in LV R- patients. SGL was -12.5 ± 5.6% in no LV R- patients and -6.5 ± 3.4 in LV R- patients. In the regression analysis just LV SGL and SL in left anterior descending territory remained significant, OR: 1.85 (1.24 to 2.76) (P < 0.001) and OR: 1.63 (1.15 to 2.31) (P < 0.001), respectively. The analysis of ROC curves revealed that at the cutoff level of -12.46%, SGL identifies LV R- with a sensibility of 81% and a specificity of 86%   with STEMI at any LV localization and subjected to primary PCI were studied during 2012: LV R- patients (1 years wSGL assessment in the first days after primary PCI is useful in the prediction of LV R- independently of the myocardial infarction localization.


Erratum: Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms1,2, Guoan Chen3, Hong Chang1,2,4Jahangir Abdi2186-2207Oncotarget. 2013; 4:PMID: 24327604http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1497&path%5B%5D=1760The affiliation of the first author is incorrect in the published paper.1 Division of Immunopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsThe corrected affiliation is provided here.1 Dept. of Laboratory Medicine & Pathobiology, University of Toronto, Ontario, Canada


Enterobacteriaceae-producing extended-spectrum β-lactamases (ESBLs). A retrospective case-control study was conducted to identify independent risk factors for ESBL-producing Escherichia coli and Klebsiella pneumoniae in non-hospitalized KTPs with UTI. Forty-nine patients suffering from UTI by ESBL-producing bacteria (ESBL-P) as case group and the same number of patients with UTI by ESBL negative (ESBL-N) as control-group were compared. Clinical data, renal function parameters during UTI episodes, UTI recurrence and relapsing rate, as well as risk factors for recurrence, molecular characterization of isolates and the respective antimicrobial susceptibility profile were evaluated. Diabetes mellitus (p <0.007), previous antibiotic prophylaxis (p=0.017) or therapy (p<0.001), previous UTI (p=0.01), relapsing infection (p=0.019) and patients with delayed graft function after transplant (p=0.001) represented risk factors for infection by ESBL positive Enterobacteriaceae in KTPs. Interestingly, the period of time between data of transplantation and data of UTI was shorter in case of ESBL-P case-group (28.8 months) compared with ESBL-N control-group (50.9 months). ESBL-producing bacteria exhibited higher resistance to fluoroquinolones (p=0.002), trimethoprim-sulfamethoxazole (p<0.001) and gentamicin (p<0.001). Molecular analysis showed that blaCTX-M was the most common ESBL encoding gene (65.3%), although in 55.1% of the cases more than one ESBL gene was found. In 29.4% of K. pneumoniae isolates, three bla-genes (blaCTX-M-blaTEM-blaSHV) were simultaneously detected. Low estimated glomerular filtration rate (p=0.009) was found to be risk factor for UTI recurrence. Over 60% of recurrent UTI episodes were caused by genetically similar strains. UTI by ESBL-producing Enterobacteriaceae in KTPs represent an important clinical challenge regarding not only hospitalized patients but also concerning outpatients.Urinary tract infection (UTI) is a common complication after kidney transplantation, often associated to graft loss and increased healthcare costs. Kidney transplant patients (KTPs) are particularly susceptible to infection by  Urinary tract infections (UTI) affect 5 to 36% of kidney transplant patients (KTPs), being the main infectious complication among such patient population –4, and oblaCTX-M [ESBLs are a large, rapidly evolving group of plasmid-enzymes that confer resistance to penicillins, first-, second-, and third generation cephalosporins, and aztreonam. They are inhibited by beta-lactamase inhibitors such as clavulanic acid –10. DurilaCTX-M . The prelaCTX-M –17. TherlaCTX-M –20, howeE. coli and K. pneumoniae comparatively to the respective non ESBL-producing counterparts. ESBLs encoding genes were identified. E. coli and K. pneumoniae isolates sequentially recovered from each patient were genotyped to assess about re-infection or bacterial persistence.The aim of this study was to identify risk factors, the susceptibility profile and recurrence associated to UTI caused by ESBL-producing This study was approved by Comissão de Etica para a Saúde (CES) do Centro Hospitalar de São João , signed by Prof. Manuel Pestana (Director of Nephrology Department). Patient records/information was anonymized and de-identified prior to analysis.E. coli and K. pneumoniae ESBL-producing bacteria (ESBL-P), as case-group, and 49 outpatients with UTI by the same species but ESBL negative (ESBL-N), as a control-group, was performed. All patients were kidney transplant patients (KTPs) from Centro Hospitalar São João, Porto  with documented UTI between January 2012 and August 2012.A retrospective case-control study enrolling 49 outpatients with UTI by 2) was registered [Demographic data  and clinical variables such as delayed graft function, the presence of urinary tract obstruction, bacteremia, fungemia, previous urinary tract infection, creatinine blood level (reference range 0.6–1.1 mg/dL), and the percentage of patients with low estimated glomerular filtration rate (eGFR) during UTI  and K. pneumoniae (n = 32) were recovered from 49 KTPs (case-group): 25 patients yielded each a single isolate, 16 patients two isolates each, 7 patients three isolates each, one single patient yielding four isolates. Forty-nine ESBL negative isolates (32 E. coli and 17 K. pneumoniae) were recovered from the 49 patients of control group. All isolates were analyzed by Vitek2 System  using GN card for identification and the AST-60 for antimicrobial susceptibility profile. ESBL presence was confirmed by disc diffusion method, according to the recommendations of Clinical Laboratory Standard Institute [Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC700603 type strains, as recommended by CLSI protocol [Eighty-two isolates of ESBL-producing nstitute ; a doublprotocol  and plasblaCTX-M,blaTEM, and blaSHV) were screened by PCR multiplex, as previously described [blaSHV: 5´-ATCCACTATCGCCAGCAGG-3´ and 5´-TCATTCAGTTCCGTTTCCCAG-3´; blaTEM: 5´-GAGTATTCAACATTTCCGTGTC-3´ and 5´-GGGCGAAAACTCTCAAGGATC-3´; blaCTX-M: 5´-GTTGTTAGGAAGTGTGCCGC-3´ and 5´-GCCCGAGGTGAAGTGGTATC-3´. Primers amplified the internal fragments of ESBLs genes possessing different sizes. Multiplex PCR was performed in a 25 μl reaction mixture containing 1x Dream Taq buffer (Fermentas), 2.5 mM MgCl2, 10 mM dNTPs, 2.5–40 pmol of specific-group primers, 50–150 ng plasmid DNA and 1 U of Dream Taq Polymerase (Fermentas). Amplification reactions were carried out in Mastercycler Realplex2 (Eppendorf) under the following conditions: initial denaturation at 95°C for 2 min, followed by 30 cycles of denaturation (95°C for 30 sec), annealing (59°C for 30 sec), extension (72° for 30 sec) and a final extension step (72°C for 10 min). PCR products were run at 80 V, during 1 hour in a 2.5% agarose gel containing 0.002% Ethidium Bromide . ESBLs bacteria exhibiting well-characterized ESBL genes kindly gift by Dr. Rafael Cantón  were used as positive controls.The most frequently ESBL genes , and involved the following steps: initial denaturation at 94°C for 1 min, followed by 45 cycles of denaturation (94°C at 1 min), annealing (34°C at 1 min), extension (72°C at 2 min), and a final extension step (72°C at 10 min). PCR products were separated by electrophoresis (60 V for 3 hours) in a 2.5% agarose gel. DNA fingerprints were compared by visual inspection with the Molecular Imager ChemiDoc XRS (BioRad). Clonality was assessed by visual inspection of the different fragments obtained, in a range of 2000–200 bp for E. coli and 3000–250 bp for K. pneumoniae. According to Wong et al. [Sequential isolates from case-group (ESBL-P)- 2 or more isolates (24 patients)—were genotyped by RAPD. Distinct primers were used for E. coli   version 20. Continuous variables were summarized as mean value and standard deviation (SD). Categorical variables, summarized as percentages, were compared using Chi-square test (or Fishers ‘exact test whenever was necessary) and Student´s Patient clinical data, including demographic characteristics, co-morbidities, clinical laboratory data, immunosuppressive therapeutic regimen, previous UTI and antibiotic exposure are summarized in Regarding immunosuppression, all patients showed adequate therapeutic levels; mean values were: 8.1 ng/mL for tacrolimus, 190.5 ng/mL for cyclosporine and 6.28 ng/mL for everolimus. Patient death occurred solely among ESBL-P group, during the 3 months after infection . No bactK. pneumoniae susceptibility to amikacin between both study groups  were detected by PCR multiplex in isolates from ESBL-P group (blaCTX-M (65.3%), either alone (18.4%) or in combination with another ESBL gene (46.9%), followed by blaTEM (61.2%) and blaSHV (40.8%). More than half of the case- group express more than one ESBL gene, being the association blaCTX-M- blaTEM the most frequent (28.5%), particularly among E. coli strains (37.5%). Among K. pneumoniae isolates, blaCTX-M-blaTEM-blaSHV (29.4%) was the most frequent association, followed by blaCTX-M-blaSHV (23.5%). Strains expressing a single ESBL gene, blaCTX-M (25%) and blaTEM (18.8%) corresponded most often to E. coli, while blaSHV was more common among K. pneumoniae isolates (17.6%) (ESBL genes (-P group . Interes (17.6%) . No corrE. coli and 63.6% in the case of K. pneumoniae) (see representative examples in Although the level of recurrence found for both groups was similar (around 40%), the relapsing percentage was significantly higher on control-group . The 48 Kidney transplant recipients display many risk factors for UTI and are considered a particular vulnerable population to such infections . Severalet al. study [blaCTX-M,blaTEM, and blaSHV) in E. coli and K. pneumoniae revealed that blaCTX-M was the most common ESBL gene. A higher predominance of blaCTX-M enzyme among ESBL positive E. coli was reported in Greece [blaCTX-M and blaTEM [E. coli and K. pneumoniae (57.3%) isolates exhibiting two or three genes was previously reported [blaSHV and blaTEM types of ESBLs have traditionally been responsible for serious health care related infections [blaCTX-M types have been mainly associated with community-onset UTI [blaCTX-M-producing bacteria and resistance to fluoroquinolones [Similar to Linares study  impairmel. study . Remarkan Greece . Conversn Greece . In Port blaTEM ,36. Repo blaTEM . A high reported , similarfections  while blnset UTI . The epinset UTI , being tinolones  such corE. coli and K. pneumoniae. Molecular epidemiology showed that blaCTX-M was the most common ESBL encoding gene, either alone or in association with other genes. Low eGFR and high blood creatinine are risk factors for UTI recurrence. The high co-resistance to other antibiotics (non-β-lactams) found from ESBL producing bacteria in UTI from KTPs, remains a serious clinical challenge.In conclusion, we have demonstrated that delayed graft function, diabetes mellitus, previous antibiotic exposure, antibiotic prophylaxis and relapsing UTI are independent risks factors for acquiring infections by ESBL-producing


Their structures and relative configurations were established by extensive spectroscopic analysis. A possible biosynthetic pathway for 1–4 was also proposed.Guajadials C-F (Supplementary material is available for this article at 10.1007/s13659-012-0102-4 and is accessible for authorized users. Supplementary material, approximately 2.05 MB.


The correct citation is: Seed Ahmed M, Pelletier J, Leumann H, Gu HF, Östenson C-G (2015) Expression of Protein Kinase C Isoforms in Pancreatic Islets and Liver of Male Goto-Kakizaki Rats, a Model of Type 2 Diabetes. PLoS ONE 10(9): e0135781. doi:


MEDI4736 is an engineered human IgG1 that blocks PD-L1 binding to PD-1 and allows T-cells to recognize and kill tumor. MEDI4736 has single-agent activity and potential for further increased activity in combination. A comprehensive development programme is underway in NSCLC, as monotherapy and in combination.NSCLC data from 2 multicentre, open-label Phase I studies are reported. NCT01693562 evaluates safety and efficacy of MEDI4736 administered every 2 or 3 weeks. NCT02000947 evaluates safety and efficacy of MEDI4736 in combination with tremelimumab, a human IgG2 anti-CTLA-4 mAb, at 4-week intervals.NCT01693562: As of May 2014, NSCLC cohort included 155 patients (pts) . Median follow-up: 6 weeks (range 0-67). Treatment-related adverse events (TRAEs): 29% (Grade [Gr] ≥3: 3%); none led to treatment discontinuation. Most frequent TRAEs: fatigue (7%), nausea (5%), and vomiting (5%). No treatment-related colitis any Gr. No treatment-related Gr 3/4 pneumonitis or dyspnea. 58 pts had ≥12 weeks follow-up: 16% had partial response (as early as 6 weeks), duration of response ranged 5-54+ weeks, disease control rate 35%. PD-L1 positivity appears to enrich for response.NCT02000947: As of April, 2014, 12 pts treated at 4 dose-levels . No DLTs observed in any cohort during DLT observation period. Most frequent TRAEs: -↑amylase, abdominal pain, arthralgia, colitis, diarrhea, epigastric discomfort, fatigue and nausea. TRAEs ≥Gr 3 noted in 3 pts: Gr 3 - ↑AST/ALT & Gr 5 myasthenia (MG) (n = 1), Gr 3 diarrhea/colitis (n = 1), Gr 4 - ↑amylase (n = 1). TRAEs led to discontinuation in two subjects: Gr 5 MG and Gr3 colitis. In 12 response-evaluable pts  support continued development in NSCLC. Additional monotherapy NSCLC studies: Phase II 'ATLANTIC' (NCT02087423), Phase III 'PACIFIC' following chemo-radiotherapy (NCT02125461), Combination: Phase I + gefitinib (NCT02088112), and Phase Ib + AZD9291 (NCT02143466). Monotherapy and combination: Phase III 'ARCTIC' vs standard-of-care.