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Berlin Brandenburg

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  • 2012  (18)
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  • 2012  (18)
  • 1
    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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  • 2
    Language: English
    In: The Journal of infectious diseases, November 2012, Vol.206(9), pp.1407-14
    Description: Haemophilus ducreyi encounters several classes of antimicrobial peptides (APs) in vivo and utilizes the sensitive-to-antimicrobial-peptides (Sap) transporter as one mechanism of AP resistance. A mutant lacking the periplasmic solute-binding component, SapA, was somewhat more sensitive to the cathelicidin LL-37 than the parent strain and was partially attenuated for virulence. The partial attenuation led us to question whether the transporter is fully abrogated in the sapA mutant. We generated a nonpolar sapBC mutant, which lacks both inner membrane permeases of the Sap transporter, and tested the mutant for virulence in human volunteers. In vitro, we compared LL-37 resistance phenotypes of the sapBC and sapA mutants. Unlike the sapA mutant, the sapBC mutant was fully attenuated for virulence in human volunteers. In vitro, the sapBC mutant exhibited significantly greater sensitivity than the sapA mutant to killing by LL-37. Similar to the sapA mutant, the sapBC mutant did not affect H. ducreyi's resistance to human defensins. Compared with the sapA mutant, the sapBC mutant exhibited greater attenuation in vivo, which directly correlated with increased sensitivity to LL-37 in vitro. These results strongly suggest that the SapBC channel retains activity when SapA is removed.
    Keywords: Drug Resistance, Bacterial ; Antimicrobial Cationic Peptides -- Pharmacology ; Haemophilus Ducreyi -- Enzymology ; Membrane Transport Proteins -- Metabolism ; Virulence Factors -- Metabolism
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 3
    Language: English
    In: Infection and immunity, December 2012, Vol.80(12), pp.4426-34
    Description: During microbial infection, macrophages are polarized to classically activated (M1) or alternatively activated (M2) cells in response to microbial components and host immune mediators. Proper polarization of macrophages is critical for bacterial clearance. To study the role of macrophage polarization during Haemophilus ducreyi infection, we analyzed a panel of macrophage surface markers in skin biopsy specimens of pustules obtained from experimentally infected volunteers. Lesional macrophages expressed markers characteristic of both M1 and M2 polarization. Monocyte-derived macrophages (MDM) also expressed a mixed M1 and M2 profile of surface markers and cytokines/chemokines upon infection with H. ducreyi in vitro. Endogenous interleukin 10 (IL-10) produced by infected MDM downregulated and enhanced expression of several M1 and M2 markers, respectively. Bacterial uptake, mediated mainly by class A scavenger receptors, and activation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathways were required for H. ducreyi-induced IL-10 production in MDM. Compared to M1 cells, IL-10-polarized M2 cells displayed enhanced phagocytic activity against H. ducreyi and similar bacterial killing. Thus, IL-10-modulated macrophage polarization may contribute to H. ducreyi clearance during human infection.
    Keywords: Chancroid -- Immunology ; Haemophilus Ducreyi -- Immunology ; Interleukin-10 -- Immunology ; Macrophage Activation -- Immunology ; Macrophages -- Classification
    E-ISSN: 1098-5522
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  • 4
    Language: English
    In: Infection and Immunity, 2012, Vol. 80(2), p.679
    Description: Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and self-recognition. The sialic acid preferentially expressed in human tissues is N-acetylneuraminic acid (Neu5Ac). In a process called molecular mimicry, many bacterial pathogens decorate their cell surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial glycolipids promotes bacterial interactions with host cell receptors called Siglecs. These interactions affect bacterial adherence, resistance to serum killing and phagocytosis, and innate immune responses. Haemophilus ducreyi, the etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are highly sialylated. However, an H. ducreyi sialyltransferase (lst) mutant, whose LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers. Recently, a second sialyltransferase gene (Hd0053) was discovered in H. ducreyi, raising the possibility that Hd0053 compensated for the loss of lst during human infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase (neuA) mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to its wild-type parent in several models of pathogenesis. In human inoculation experiments, the neuA mutant formed papules and pustules at rates that were no different than those of its parent. When grown in media with and without Neu5Ac supplementation, the neuA mutant and its parent had similar phenotypes in bactericidal, macrophage uptake, and dendritic cell activation assays. Although we cannot preclude a contribution of LOS sialylation to ulcerative disease, these data strongly suggest that sialylation of LOS is dispensable for H. ducreyi pathogenesis in humans.
    Keywords: Bacterial Proteins -- Metabolism ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Metabolism ; Lipopolysaccharides -- Metabolism ; N-Acetylneuraminic Acid -- Metabolism;
    ISSN: 1098-5522
    ISSN: 10985522
    ISSN: 00199567
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  • 5
    Language: English
    In: Patient Education and Counseling, October 2012, Vol.89(1), pp.184-190
    Description: To evaluate (PC), a program that employed lay health workers to motivate antiretroviral adherence among persons living with HIV with coverage from Indiana's high-risk insurance pool. Four hundred and forty nine participants living in the greater Indianapolis area were randomly allocated to treatment ( = 91) or control ( = 358) groups and followed for one year. Compared to control subjects, PC subjects were more likely to adhere to HIV medications (medication possession ratio adherence ≥0.95, OR = 1.83, = 0.046), and to achieve undetectable viral load (〈50 copies/mL, OR = 2.01, = 0.011) in the 12 months following introduction of PC. There were no significant differences observed between groups in any of self-reported health status indicators. Estimates suggest that PC clients were 16% more likely to have undetectable viral loads than clients in standard care. The incremental program cost was approximately $10,000 for each additional person who achieved an undetectable viral load. As persons living with HIV experience greater longevity and healthcare reform expands coverage to these high-risk populations, greater demands will be placed on the HIV-care workforce. Results suggest lay health workers may serve as effective adjuncts to professional care providers.
    Keywords: Lay Health Workers ; Medication Adherence ; HIV ; Medicine ; Public Health
    ISSN: 0738-3991
    E-ISSN: 1873-5134
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  • 6
    In: Radiation Research, 2012, Vol.179(1), p.89-100
    Description: Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n 22) or filgrastim-treated (n 24) cohorts. Filgrastim (10 g/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was 〉1,000/L for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P 〈 0.004) reduced 60 day overall mortality 20.8 (5/24) compared to the controls 59.1 (13/22). Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC 〈500/L and body temperature 103F) was experienced by 90.9 (20/22) of controls compared to 79.2 (19/24) of filgrastim-treated animals (P 0.418). Survival was significantly increased by 38.3 over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome.
    Keywords: Engineering ; Biology ; Physics;
    ISSN: 0033-7587
    E-ISSN: 19385404
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  • 7
    In: Health Physics, 2012, Vol.103(4), pp.383-399
    Description: ABSTRACT: The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing, and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources, and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data, the authors have generated dose response data in adult male mice maintained under identical conditions and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow, and lung) in the surviving mice. Lethal dose (LD30, LD50, and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. These data can be used to aid the design of good laboratory practice (GLP)-compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure.
    Keywords: Acute Radiation Syndrome -- Etiology ; Gastrointestinal Diseases -- Etiology ; Radiation Injuries, Experimental -- Etiology ; Whole-Body Irradiation -- Adverse Effects;
    ISSN: 0017-9078
    E-ISSN: 15385159
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  • 8
    Language: English
    In: Sexual health, September 2012, Vol.9(4), pp.299-303
    Description: This study examined young women's actual timing of use of a microbicide surrogate gel (vaginal moisturiser (VM)) compared with assigned timing conditions. Participants used a VM with coitus during 4-week cycles over a 3-year period in random timing sequences: 1h before coitus, 10 min before coitus and 10 min after coitus. Daily diaries collected information related to coital behaviours, VM use and timing, and participants' and partners' VM assessments. Descriptive and mixed-effects model analyses were conducted. At least three VM timing conditions were completed by 109 women aged 18-22 years old. Of 17?772 diary days collected, coitus was reported on 2128 (1252 with VM use; 59%). Median times between VM application and coitus were: 60 min before coitus (mean=68.2; s.d.=76.9) for the 1-h pre-coital group, 13.5 min before coitus (mean=44.9; s.d.=117.1) for the 10-min pre-coital group and 5 min before coitus (mean=24.5; s.d.=205.1) for the 10-min post-coital group. Women reported that the VM was very easy to use (68%), it was somewhat messy (61%), they were very wet during sex (81%), sex was very good (80%) and their partners liked using the VM (38%). Overall, the VM was rated positively. There was substantial deviation in application time across timing conditions, with significantly greater variability in the post-coital group. These findings contribute to understanding of how VMs are accepted and used, with implications for HIV prevention with microbicides requiring specific application timing.
    Keywords: Coitus ; Anti-Infective Agents, Local -- Administration & Dosage ; HIV Infections -- Prevention & Control ; Sexually Transmitted Diseases -- Prevention & Control
    ISSN: 1448-5028
    E-ISSN: 14498987
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  • 9
    In: Health Physics, 2012, Vol.103(4), pp.356-366
    Description: ABSTRACT: Residual bone marrow damage (RBMD) persists for years following exposure to radiation and is believed to be due to decreased self-renewal potential of radiation-damaged hematopoietic stem cells (HSC). Current literature has examined primarily sublethal doses of radiation and time points within a few months of exposure. In this study, the authors examined RBMD in mice surviving lethal doses of total body ionizing irradiation (TBI) in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS). Survivors were analyzed at various time points up to 19 mo post-TBI for hematopoietic function. The competitive bone marrow (BM) repopulating potential of 150 purified c-Kit+ Sca-1+ lineage- CD150+ cells (KSLCD150+) remained severely deficient throughout the study compared to KSLCD150+ cells from non-TBI age-matched controls. The minimal engraftment from these TBI HSCs is predominantly myeloid, with minimal production of lymphocytes both in vitro and in vivo. All classes of blood cells as well as BM cellularity were significantly decreased in TBI mice, especially at later time points as mice aged. Primitive BM hematopoietic cells (KSLCD150+) displayed significantly increased cell cycling in TBI mice at all time points, which may be a physiological attempt to maintain HSC numbers in the post-irradiation state. Taken together, these data suggest that the increased cycling among primitive hematopoietic cells in survivors of lethal radiation may contribute to long-term HSC exhaustion and subsequent RBMD, exacerbated by the added insult of aging at later time points.
    Keywords: Acute Radiation Syndrome -- Etiology ; Hematopoietic Stem Cells -- Radiation Effects ; Radiation Injuries, Experimental -- Etiology ; Whole-Body Irradiation -- Adverse Effects;
    ISSN: 0017-9078
    E-ISSN: 15385159
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  • 10
    In: Health Physics, 2012, Vol.103(4), pp.367-382
    Description: ABSTRACT: The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min. Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.
    Keywords: Radiation ; Health Physics ; Disease Management ; Primates ; Morbidity ; Mortality;
    ISSN: 0017-9078
    E-ISSN: 15385159
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