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Berlin Brandenburg

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  • 1
    Language: English
    In: PloS one, 2015, Vol.10(4), pp.e0124373
    Description: Haemophilus ducreyi resists the cytotoxic effects of human antimicrobial peptides (APs), including α-defensins, β-defensins, and the cathelicidin LL-37. Resistance to LL-37, mediated by the sensitive to antimicrobial peptide (Sap) transporter, is required for H. ducreyi virulence in humans. Cationic APs are attracted to the negatively charged bacterial cell surface. In other gram-negative bacteria, modification of lipopolysaccharide or lipooligosaccharide (LOS) by the addition of positively charged moieties, such as phosphoethanolamine (PEA), confers AP resistance by means of electrostatic repulsion. H. ducreyi LOS has PEA modifications at two sites, and we identified three genes (lptA, ptdA, and ptdB) in H. ducreyi with homology to a family of bacterial PEA transferases. We generated non-polar, unmarked mutants with deletions in one, two, or all three putative PEA transferase genes. The triple mutant was significantly more susceptible to both α- and β-defensins; complementation of all three genes restored parental levels of AP resistance. Deletion of all three PEA transferase genes also resulted in a significant increase in the negativity of the mutant cell surface. Mass spectrometric analysis revealed that LptA was required for PEA modification of lipid A; PtdA and PtdB did not affect PEA modification of LOS. In human inoculation experiments, the triple mutant was as virulent as its parent strain. While this is the first identified mechanism of resistance to α-defensins in H. ducreyi, our in vivo data suggest that resistance to cathelicidin LL-37 may be more important than defensin resistance to H. ducreyi pathogenesis.
    Keywords: Bacterial Proteins -- Genetics ; Drug Resistance, Bacterial -- Genetics ; Ethanolaminephosphotransferase -- Genetics ; Haemophilus Ducreyi -- Genetics ; Lipid A -- Metabolism
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: PLoS ONE, 2012, Vol.7(5), p.e36298
    Description: Lactobacillus- dominated vaginal microbiotas are associated with reproductive health and STI resistance in women, whereas altered microbiotas are associated with bacterial vaginosis (BV), STI risk and poor reproductive outcomes. Putative vaginal taxa have been observed in male first-catch urine, urethral swab and coronal sulcus (CS) specimens but the significance of these observations is unclear. We used 16 S rRNA sequencing to characterize the microbiota of the CS and urine collected from 18 adolescent men over three consecutive months. CS microbiotas of most participants were more stable than their urine microbiotas and the composition of CS microbiotas were strongly influenced by circumcision. BV-associated taxa, including Atopobium , Megasphaera , Mobiluncus , Prevotella and Gemella , were detected in CS specimens from sexually experienced and inexperienced participants. In contrast, urine primarily contained taxa that were not abundant in CS specimens. Lactobacilllus and Streptococcus were major urine taxa but their abundance was inversely correlated. In contrast, Sneathia , Mycoplasma and Ureaplasma were only found in urine from sexually active participants. Thus, the CS and urine support stable and distinct bacterial communities. Finally, our results suggest that the penis and the urethra can be colonized by a variety of BV-associated taxa and that some of these colonizations result from partnered sexual activity.
    Keywords: Research Article ; Biology ; Medicine ; Public Health And Epidemiology ; Infectious Diseases ; Microbiology ; Urology
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: Pediatrics, February 2011, Vol.127(2), pp.e336-44
    Description: We assessed differences in chlamydia screening rates according to race/ethnicity, insurance status, age, and previous sexually transmitted infection (STI) or pregnancy. A retrospective cohort study was performed using electronic medical record and billing data for women 14 to 25 years of age in 2002-2007, assessing differences in the odds of a chlamydia test being performed at that visit. Adjusted odds of a chlamydia test being performed were lower among women 14 to 15 years of age (odds ratio: 0.83 [95% confidence interval: 0.70-1.00]) and 20 to 25 years of age (20-21 years, odds ratio: 0.78 [95% confidence interval: 0.70-0.89]; 22-23 years, odds ratio: 0.76 [95% confidence interval: 0.67-0.87]; 24-25 years, odds ratio: 0.64 [95% confidence interval: 0.57-0.73]), compared with women 18 to 19 years of age. Black women had 3 times increased odds (odds ratio: 2.96 [95% confidence interval: 2.66-3.28]) and Hispanic women nearly 13 times increased odds (odds ratio: 12.89 [95% confidence interval: 10.85-15.30]) of testing, compared with white women. Women with public (odds ratio: 1.74 [95% confidence interval: 1.58-1.91]) and public pending (odds ratio: 6.85 [95% confidence interval: 5.13-9.15]) insurance had increased odds of testing, compared with women with private insurance. After first STI diagnosis, differences according to race/ethnicity persisted but were smaller; after first pregnancy, differences persisted. Despite recommendations to screen all sexually active young women for chlamydia, providers screened women differently according to age, race/ethnicity, and insurance status, although differences were reduced after first STI or pregnancy.
    Keywords: Chlamydia Infections -- Diagnosis ; Health Personnel -- Standards ; Mass Screening -- Methods
    ISSN: 00314005
    E-ISSN: 1098-4275
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  • 4
    Language: English
    In: Disease models & mechanisms, 01 April 2017, Vol.10(4), pp.425-437
    Description: Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 h post-exposure demonstrated 〉5000 genes to be differentially expressed (twofold change) between strains with early versus late onset of disease. An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis, DNA replication and cell division. At 24 h post-WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains but microscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with the macroscopic expression of injury manifesting weeks to months after exposure. Understanding the mechanisms underlying development of RILD might lead to more rational selection of therapeutic interventions to mitigate healthy tissue damage.
    Keywords: Gene Expression Profiling ; Lung Fibrosis ; Murine Strain Differences ; Radiation Pneumonitis ; Disease Progression ; Gene Expression Profiling ; Lung Diseases -- Genetics ; Radiation Injuries -- Genetics
    ISSN: 17548403
    E-ISSN: 1754-8411
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  • 5
    Language: English
    In: BMC Microbiology, Sept 22, 2011, Vol.11, p.208
    Description: Background Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein) operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF). A tadA mutant is attenuated in its ability to cause disease in human volunteers and in the temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits. Whether a flp deletion mutant would cause disease in humans is not clear. Results We constructed 35000HP[DELTA]flp1-3, a deletion mutant that lacks expression of all three Flp proteins but has an intact tad secretion system. 35000HP[DELTA]flp1-3 was impaired in its ability to form microcolonies and to attach to HFF in vitro when compared to its parent (35000HP). Complementation of the mutant with flp1-3 in trans restored the parental phenotype. To test whether expression of Flp1-3 was necessary for virulence in humans, ten healthy adult volunteers were experimentally infected with a fixed dose of 35000HP (ranging from 54 to 67 CFU) on one arm and three doses of 35000HP[DELTA]flp1-3 (ranging from 63 to 961 CFU) on the other arm. The overall papule formation rate for the parent was 80% (95% confidence interval, CI, 55.2%-99.9%) and for the mutant was 70.0% (95% CI, 50.5%-89.5%) (P = 0.52). Mutant papules were significantly smaller (mean, 11.2 mm.sup.2.sup.) than were parent papules (21.8 mm.sup.2.sup.) 24 h after inoculation (P = 0.018). The overall pustule formation rates were 46.7% (95% CI 23.7-69.7%) at 30 parent sites and 6.7% (95% CI, 0.1-19.1%) at 30 mutant sites (P = 0.001). Conclusion These data suggest that production and secretion of the Flp proteins contributes to microcolony formation and attachment to HFF cells in vitro. Expression of flp1-3 is also necessary for H. ducreyi to initiate disease and progress to pustule formation in humans. Future studies will focus on how Flp proteins contribute to microcolony formation and attachment in vivo.
    Keywords: Hemophilus Infections -- Genetic Aspects ; Hemophilus Infections -- Health Aspects ; Hemophilus Infections -- Research
    ISSN: 1471-2180
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: BMC Microbiology, Sept 22, 2011, Vol.11, p.208
    Description: Background Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein) operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF). A tadA mutant is attenuated in its ability to cause disease in human volunteers and in the temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits. Whether a flp deletion mutant would cause disease in humans is not clear. Results We constructed 35000HP[DELTA]flp1-3, a deletion mutant that lacks expression of all three Flp proteins but has an intact tad secretion system. 35000HP[DELTA]flp1-3 was impaired in its ability to form microcolonies and to attach to HFF in vitro when compared to its parent (35000HP). Complementation of the mutant with flp1-3 in trans restored the parental phenotype. To test whether expression of Flp1-3 was necessary for virulence in humans, ten healthy adult volunteers were experimentally infected with a fixed dose of 35000HP (ranging from 54 to 67 CFU) on one arm and three doses of 35000HP[DELTA]flp1-3 (ranging from 63 to 961 CFU) on the other arm. The overall papule formation rate for the parent was 80% (95% confidence interval, CI, 55.2%-99.9%) and for the mutant was 70.0% (95% CI, 50.5%-89.5%) (P = 0.52). Mutant papules were significantly smaller (mean, 11.2 mm.sup.2.sup.) than were parent papules (21.8 mm.sup.2.sup.) 24 h after inoculation (P = 0.018). The overall pustule formation rates were 46.7% (95% CI 23.7-69.7%) at 30 parent sites and 6.7% (95% CI, 0.1-19.1%) at 30 mutant sites (P = 0.001). Conclusion These data suggest that production and secretion of the Flp proteins contributes to microcolony formation and attachment to HFF cells in vitro. Expression of flp1-3 is also necessary for H. ducreyi to initiate disease and progress to pustule formation in humans. Future studies will focus on how Flp proteins contribute to microcolony formation and attachment in vivo.
    Keywords: Hemophilus Infections -- Genetic Aspects ; Hemophilus Infections -- Health Aspects ; Hemophilus Infections -- Research
    ISSN: 1471-2180
    Source: Cengage Learning, Inc.
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  • 7
    Language: English
    In: BMC microbiology, 24 June 2014, Vol.14, pp.166
    Description: Bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. Such lipoproteins are viable vaccine candidates. Haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. One such lipoprotein, OmpP4, is homologous to the outer membrane lipoprotein e (P4) of H. influenzae. In H. influenzae, e (P4) stimulates production of bactericidal and protective antibodies and contributes to pathogenesis by facilitating acquisition of the essential nutrients heme and nicotinamide adenine dinucleotide (NAD). Here, we tested the hypothesis that, like its homolog, H. ducreyi OmpP4 contributes to virulence and stimulates production of bactericidal antibodies. We determined that OmpP4 is broadly conserved among clinical isolates of H. ducreyi. We next constructed and characterized an isogenic ompP4 mutant, designated 35000HPompP4, in H. ducreyi strain 35000HP. To test whether OmpP4 was necessary for virulence in humans, eight healthy adults were experimentally infected. Each subject was inoculated with a fixed dose of 35000HP on one arm and three doses of 35000HPompP4 on the other arm. The overall parent and mutant pustule formation rates were 52.4% and 47.6%, respectively (P = 0.74). These results indicate that expression of OmpP4 in not necessary for H. ducreyi to initiate disease or progress to pustule formation in humans. Hyperimmune mouse serum raised against purified, recombinant OmpP4 did not promote bactericidal killing of 35000HP or phagocytosis by J774A.1 mouse macrophages in serum bactericidal and phagocytosis assays, respectively. Our data suggest that, unlike e (P4), H. ducreyi OmpP4 is not a suitable vaccine candidate. OmpP4 may be dispensable for virulence because of redundant mechanisms in H. ducreyi for heme acquisition and NAD utilization.
    Keywords: Bacterial Outer Membrane Proteins -- Metabolism ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Pathogenicity ; Virulence Factors -- Metabolism
    E-ISSN: 1471-2180
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  • 8
    Language: English
    In: BMC medicine, 06 November 2014, Vol.12, pp.204
    Description: Nearly 1 in 5 people living with HIV in the United States are unaware they are infected. Therefore, it is important to develop and evaluate health communication messages that clinicians can use to encourage HIV testing. The objective was to evaluate health communication messages designed to increase HIV testing rates among women and evaluate possible moderators of message effect. We used a randomized four-arm clinical trial conducted at urban community outpatient health clinics involving 1,919 female patients, 18 to 64 years old. The four health message intervention groups were: i) information-only control; ii) one-sided message describing the advantages of HIV testing; iii) two-sided message acknowledging a superficial objection to testing (i.e., a 20 minute wait for results) followed by a description of the advantages of testing; and iv) two-sided message acknowledging a serious objection (i.e., fear of testing positive for HIV) followed by a description of the advantages of testing. The main outcome was acceptance of an oral rapid HIV test. Participants were randomized to receive the control message (n = 483), one-sided message (n = 480), two-sided message with a superficial objection (n = 481), or two-sided message with a serious objection (n = 475). The overall rate of HIV test acceptance was 83%. The two-sided message groups were not significantly different from the controls. The one-sided message group, however, had a lower rate of testing (80%) than the controls (86%) (OR, 0.66; 95% CI, 0.47-0.93; P = 0.018). "Perceived obstacles to HIV testing" moderated this effect, indicating that the decrease in HIV test acceptance for the one-sided message group was only statistically significant for those who had reported high levels of obstacles to HIV testing (OR, 0.36; 95% CI, 0.19-0.67; P = 0.001). None of the messages increased test acceptance. The one-sided message decreased acceptance and this effect was particularly true for women with greater perceived obstacles to testing, the very group one would most want to persuade. This finding suggests that efforts to persuade those who are reluctant to get tested, in some circumstances, may have unanticipated negative effects. Other approaches to messaging around HIV testing should be investigated, particularly with diverse, behaviorally high-risk populations. Clinicaltrials.gov Identifier: NCT00771537. Registration date: October 10. 2008.
    Keywords: HIV Infections -- Diagnosis ; Mass Screening -- Statistics & Numerical Data ; Patient Acceptance of Health Care -- Statistics & Numerical Data ; Patient Education As Topic -- Methods
    E-ISSN: 1741-7015
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  • 9
    Language: English
    In: Sports medicine (Auckland, N.Z.), July 2018, Vol.48(7), pp.1761
    Description: The article Test-Retest Reliability and Interpretation of Common Concussion Assessment Tools.
    Keywords: Medicine & Public Health ; Sports Medicine ; Medicine;
    ISSN: 01121642
    E-ISSN: 1179-2035
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  • 10
    Language: English
    In: Sports Medicine, 2018, Vol.48(5), pp.1255-1268
    Description: Background Concussion diagnosis is typically made through clinical examination and supported by performance on clinical assessment tools. Performance on commonly implemented and emerging assessment tools is known to vary between administrations, in the absence of concussion. Objective To evaluate the test-retest reliability of commonly implemented and emerging concussion assessment tools across a large nationally representative sample of student-athletes. Methods Participants ( n  = 4874) from the Concussion Assessment, Research, and Education Consortium completed annual baseline assessments on two or three occasions. Each assessment included measures of self-reported concussion symptoms, motor control, brief and extended neurocognitive function, reaction time, oculomotor/oculovestibular function, and quality of life. Consistency between years 1 and 2 and 1 and 3 were estimated using intraclass correlation coefficients or Kappa and effect sizes (Cohen’s d ). Clinical interpretation guidelines were also generated using confidence intervals to account for non-normally distributed data. Results Reliability for the self-reported concussion symptoms, motor control, and brief and extended neurocognitive assessments from year 1 to 2 ranged from 0.30 to 0.72 while effect sizes ranged from 0.01 to 0.28 (i.e., small). The reliability for these same measures ranged from 0.34 to 0.66 for the year 1–3 interval with effect sizes ranging from 0.05 to 0.42 (i.e., small to less than medium). The year 1–2 reliability for the reaction time, oculomotor/oculovestibular function, and quality-of-life measures ranged from 0.28 to 0.74 with effect sizes from 0.01 to 0.38 (i.e., small to less than medium effects). Conclusions This investigation noted less than optimal reliability for most common and emerging concussion assessment tools. Despite this finding, their use is still necessitated by the absence of a gold standard diagnostic measure, with the ultimate goal of developing more refined and sound tools for clinical use. Clinical interpretation guidelines are provided for the clinician to apply with a degree of certainty in application. Electronic supplementary material The online version of this article (10.1007/s40279-017-0813-0) contains supplementary material, which is available to authorized users.
    Keywords: Original Research Article;
    ISSN: 0112-1642
    E-ISSN: 1179-2035
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