382 research outputs found

    Dual Orientation of the Outer Membrane Lipoprotein P6 of Nontypeable Haemophilus influenzae

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    The majority of outer membrane (OM) lipoproteins in Gram-negative bacteria are tethered to the membrane via an attached lipid moiety and oriented facing in toward the periplasmic space; a few lipoproteins have been shown to be surface exposed. The outer membrane lipoprotein P6 from the Gram-negative pathogenic bacterium nontypeable Haemophilus influenzae (NTHi) is surface exposed and a leading vaccine candidate for prevention of NTHi infections. However, we recently found that P6 is not a transmembrane protein as previously thought (L. V. Michel, B. Kalmeta, M. McCreary, J. Snyder, P. Craig, M. E. Pichichero, Vaccine 29:1624–1627, 2011). Here we pursued studies to show that P6 has a dual orientation, existing infrequently as surface exposed and predominantly as internally oriented toward the periplasmic space. Flow cytometry using three monoclonal antibodies with specificity for P6 showed surface staining of whole NTHi cells. Confocal microscopy imaging confirmed that antibodies targeted surface-exposed P6 of intact NTHi cells and not internal P6 in membrane-compromised or dead cells. Western blots of two wild-type NTHi strains and a mutant NTHi strain that does not express P6 showed that P6 antibodies do not detect a promiscuous epitope on NTHi. Depletion of targets to nonlipidated P6 significantly decreased bactericidal activity of human serum. Protease digestion of surface-exposed P6 demonstrated that P6 is predominantly internally localized in a manner similar to its homologue Pal in Escherichia coli. We conclude that P6 of NTHi is likely inserted into the OM in two distinct orientations, with the predominant orientation facing in toward the periplasm

    Unregulated Custody Transfers: Why the Practice of Rehoming Should Be Considered a Form of Illegal Adoption and Human Trafficking

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    In this work, the authors prepared and characterized two different graphene oxides: one chemically synthesized (GO sample) and the other one electrochemically synthesized (GO(LiCl)). Both samples were fully characterized with atomic force microscopy (AFM), Raman and Fourier transform infrared (FTIR) spectroscopies, X-ray photo electron spectroscopy (XPS), thermal analysis (TG/DTA), and Z-potential. The antibacterial properties of both graphene oxides were studied using Gram-negative Escherichia coli ATCC 25922 and Gram-positive Staphylococcus aureus ATCC 25923 by spectrophotometer and viable cell count as indirect and direct methods, respectively. Results demonstrated that the GO(LiCl) exhibited a significant antibacterial activity compared to GO that showed a bacteriostatic effect on both pathogens. Electron microscopy analysis confirmed the antibacterial effects of both graphene oxides toward the pathogens, especially working at 80 μg/mL, for 24 h. Additional studies were also performed and both GO samples were not cytotoxic at 2 μg/mL toward neuroblastoma cells. Moreover, 2 μg of GO was suitable to carry the minimum effective dose (5.74 ng/mL) of kinase inhibitor S29 (1-(2-chloro-2-(4-chlorophenyl)ethyl)-N-(4-fluorobenzyl)-1H-pyrazolo[3,4-d] pyrimidin-4-amine), providing negligible side effects related to the S29 treatment (this latter being specifically active on the neuroblastoma cell lines (SK-N-BE(2)))

    Safety and Efficacy of Gatifloxacin Therapy for Children with Recurrent Acute Otitis Media (AOM) and/or AOM Treatment Failure

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    Background. Because of concerns about arthrotoxicity, fluoroquinolones are restricted for use in children. This study describes the safety and efficacy of gatifloxacin when used for treatment of children with recurrent acute otitis media (ROM) or acute otitis media (AOM) treatment failure (AOMTF). Methods. We performed an analysis of 867 children included in 4 clinical trials who had ROM and/or AOMTF and were treated with gatifloxacin (10 mg/kg once daily for 10 days). Results. Gatifloxacin had adverse event rates that were similar overall to those of a comparator antibiotic (amoxicillin-clavulanate), except for increased diarrhea in children !2 years old receiving amoxicillin-clavulanate. There was no evidence of arthrotoxicity, hepatotoxicity, alteration of glucose homeostasis, or central nervous system toxicity acutely or during 1 year follow-up in any child. Regarding efficacy, in 2 noncomparative trials, the gatifloxacin cure rate of AOM was 89% (95% confidence interval [CI], 83%-95%) at the test of cure (TOC) visit, 3-10 days after completion of therapy. In 2 comparative trials of gatifloxacin versus amoxicillin-clavulanate, the efficacy of gatifloxacin was 88% (95% CI, 82%-94%). Gatifloxacin led to better clinical outcomes than amoxicillinclavulanate for AOMTF (91% vs. 81%; ), for AOMTF and age !2 years old (89% vs. 69%; ), P p .029 P p .009 and for severe AOM in children !2 years old (90% vs. 75%; ). Among children with AOMTF previously P p .012 treated with amoxicillin-clavulanate or ceftriaxone injections, gatifloxacin cure rates were high (88% and 75%, respectively). Conclusions. Gatifloxacin appears to be safe for children, with no evidence of producing arthrotoxicity in 867 children exposed to the antibiotic when used as treatment for ROM and AOMTF

    Honey as a complementary medicine

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    The beneficial effects of honey on human health have long been recognized. Today, many of those positive effects have been studied to elucidate its mode of action. This review briefly summarizes the best studied features of honey, highlighting it as an appealing alternative medicine. In these reports, the health benefits of honey range from antioxidant, immunomodulatory, and anti-inflammatory activity to anticancer action, metabolic and cardiovascular benefits, prebiotic properties, human pathogen control, and antiviral activity. These studies also support that the honey's biological activity is mainly dependent on its floral or geographic origin. In addition, some promising synergies between honey and antibiotics have been found, as well as some antiviral properties that require further investigation. Altogether, these studies show that honey is effectively a nutraceutical foodstuff.info:eu-repo/semantics/publishedVersio

    Antimicrobial-Drug Prescription in Ambulatory Care Settings, United States, 1992–2000

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    During the 1990s, as antimicrobial resistance increased among pneumococci, many organizations promoted appropriate antimicrobial use to combat resistance. We analyzed data from the National Ambulatory Medical Care Survey, an annual sample survey of visits to office-based physicians, and the National Hospital Ambulatory Medical Care Survey, an annual sample survey of visits to hospital emergency and outpatient departments, to describe trends in antimicrobial prescribing from 1992 to 2000 in the United States. Approximately 1,100–1,900 physicians reported data from 21,000–37,000 visits; 200–300 outpatient departments reported data for 28,000–35,000 visits; ~400 emergency departments reported data for 21,000–36,000 visits each year. In that period, the population- and visit-based antimicrobial prescribing rates in ambulatory care settings decreased by 23% and 25%, respectively, driven largely by a decrease in prescribing by office-based physicians. Antimicrobial prescribing rates changed as follows: amoxicillin and ampicillin, –43%; cephalosporins, –28%; erythromycin, –76%; azithromycin and clarithromycin, +388%; quinolones, +78%; and amoxicillin/clavulanate, +72%. This increasing use of azithromycin, clarithromycin, and quinolones warrants concern as macrolide- and fluoroquinolone-resistant pneumococci are increasing

    Diagnostic accuracy of non-specialist versus specialist health workers in diagnosing hearing loss and ear disease in Malawi.

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    OBJECTIVE: To determine whether a non-specialist health worker can accurately undertake audiometry and otoscopy, the essential clinical examinations in a survey of hearing loss, instead of a highly skilled specialist (i.e. ENT or audiologist). METHODS: A clinic-based diagnostic accuracy study was conducted in Malawi. Consecutively sampled participants ≥ 18 years had their hearing tested using a validated tablet-based audiometer (hearTest) by an audiologist (gold standard), an audiology officer, a nurse and a community health worker (CHW). Otoscopy for diagnosis of ear pathologies was conducted by an ENT specialist (gold standard), an ENT clinical officer, a CHW, an ENT nurse and a general nurse. Sensitivity, specificity and kappa (κ) were calculated. 80% sensitivity, 70% specificity and kappa of 0.6 were considered adequate. RESULTS: Six hundred and seventeen participants were included. High sensitivity (>90%) and specificity (>85%) in detecting bilateral hearing loss was obtained by all non-specialists. For otoscopy, sensitivity and specificity were >80% for all non-specialists in diagnosing any pathology except for the ENT nurse. Agreement in diagnoses for the ENT clinical officer was good (κ = 0.7) in both ears. For other assessors, moderate agreement was found (κ = 0.5). CONCLUSION: A non-specialist can be trained to accurately assess hearing using mobile-based audiometry. However, accurate diagnosis of ear conditions requires at least an ENT clinical officer (or equivalent). Conducting surveys of hearing loss with non-specialists could lower costs and increase data collection, particularly in low- and middle-income countries, where ENT specialists are scarce

    Primary and booster vaccination in Latin American children with a DTPw-HBV/Hib combination: a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and <it>Haemophilus influenzae </it>type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (<it>Tritanrix</it>™-HBV/Hib).</p> <p>Methods</p> <p>This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months.</p> <p>Results</p> <p>One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses.</p> <p>Conclusions</p> <p>Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs.</p> <p>Trial registration</p> <p><url>http://www.clinicaltrials.gov</url> NCT00332566</p

    Non-capsulated and capsulated Haemophilus influenzae in children with acute otitis media in Venezuela: a prospective epidemiological study

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    <p>Abstract</p> <p>Background</p> <p>Non-typeable <it>Haemophilus influenzae </it>(NTHi) and <it>Streptococcus pneumoniae </it>are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age.</p> <p>Methods</p> <p>Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes).</p> <p>Results</p> <p>Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (<it>S. pneumoniae, H. influenzae, S. pyogenes </it>or <it>M. catarrhalis</it>) was cultured from 65.9% (60/91) of episodes. <it>H. influenzae </it>(55.5%; 35/63 episodes) and <it>S. pneumoniae </it>(34.9%; 22/63 episodes) were the most frequently reported bacteria. Among <it>H. influenzae </it>isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for <it>H. influenzae </it>was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six <it>H. influenzae </it>positive samples (66.7%) from recurrent episodes.</p> <p>Conclusions</p> <p>We found <it>H. influenzae </it>and <it>S. pneumoniae </it>to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.</p
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