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BACKGROUND: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. RESULTS: Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers. CONCLUSIONS: The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.
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Due to their widespread use and subsequent release, engineered nanomaterials (ENMs) will create complex mixtures and emergent systems in the natural environment where their chemical interactions may cause toxic stress to microorganisms. We previously showed that under dark conditions n-TiO2 attenuated bacterial stress caused by low concentrations of n-Ag (<20 µg L-1) due to Ag+ adsorption, yet, since both n-Ag and n-TiO2 are photoactive, their photochemistries may play a key role in their interactions. In this work, we study the chemical interactions of n-Ag and n-TiO2 mixtures in a natural aqueous medium under simulated solar irradiation to investigate photoinduced stress. Using ATP levels and cell membrane integrity as probes, we observe that n-Ag and n-TiO2 together exert synergistic toxic stress in Escherichia coli. We find increased production of hydrogen peroxide by the n-Ag/n-TiO2 mixture, revealing that the enhanced photocatalytic activity and production of ROS likely contribute to the stress response observed. Based on STEM-EDS evidence, we propose that a new composite Ag/TiO2 nanomaterial forms under these conditions and explains the synergistic effects of the ENM mixture. Overall, this work reveals that environmental transformations of ENM mixtures under irradiation can enhance biological stress beyond that of individual components.
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Nanoestructuras , Plata , Bacterias , Escherichia coli , Luz , TitanioRESUMEN
BACKGROUND: Currently there is an urgent need to develop new classes of antimicrobial agents with different mechanisms of action from conventionally antibiotics used for the control of pathogenic microorganisms. The acylpolyamine called VdTX-I was isolated from the venom of the tarantula Vitalius dubius, and first described with activity as an antagonist of nicotinic cholinergic receptors. The main objective of this study was to investigate the antimicrobial activity found in the venom of the spider, with emphasis on the toxin VdTX-I. METHODS: Antimicrobial assays were performed in 96 well plates culture against 14 micro-organisms (fungi, yeasts and bacteria), which were tested concentrations from 0.19 to 100 µM of VdTX-I. After qualitative analysis, dose-response curve assays were performed in bacterial kill curve using MTT reagent and hemolytic assay. RESULTS: The antimicrobial activity of the VdTX-I toxin was observed in 12 tested species of Candida, Trichosporiun, Staphylococcus and Micrococcus. The toxicity had a dose-response at 3.12 µM - 100 µM in Candida albicans, Candida guillermondii, Micrococcus luteus and Escherichia coli. VdTX-I took about 5 min to inhibit bacterial growth, which was faster than streptomycin. The toxin showed no hemolytic activity between 0.19 and 100 µM. At 2.5 µg/mL of toxin it was observed no growth inhibition against a mammalian cell lineage. CONCLUSIONS: The VdTX-I toxin has a significant antimicrobial activity, with broad spectrum, and is experimentally inert to mammalian blood cells. GENERAL SIGNIFICANCE: This paper explores the antimicrobial potential of the spider toxin VdTX-I, which can provide a new model to design new antimicrobial drugs.
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Karyotypic evolution is a well-known phenomenon in patients with malignant hematological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hematological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes [46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome [46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hematological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease.
