Significantly reduced CCR5-tropic HIV-1 replication in vitro in cells from subjects previously immunized with Vaccinia Virus

<p>Abstract</p> <p>Background</p> <p>At present, the relatively sudden appearance and explosive spread of HIV throughout Africa and around the world beginning in the 1950s has never been adequately explained. Theorizing that this phenomenon may be somehow related to the eradication of smallpox followed by the cessation of vaccinia immunization, we undertook a comparison of HIV-1 susceptibility in the peripheral blood mononuclear cells from subjects immunized with the vaccinia virus to those from vaccinia naive donors.</p> <p>Results</p> <p>Vaccinia immunization in the preceding 3-6 months resulted in an up to 5-fold reduction in CCR5-tropic but not in CXCR4-tropic HIV-1 replication in the cells from vaccinated subjects. The addition of autologous serum to the cell cultures resulted in enhanced R5 HIV-1 replication in the cells from unvaccinated, but not vaccinated subjects. There were no significant differences in the concentrations of MIP-1α, MIP-1β and RANTES between the cell cultures derived from vaccinated and unvaccinated subjects when measured in culture medium on days 2 and 5 following R5 HIV-1 challenge.</p> <p>Discussion</p> <p>Since primary HIV-1 infections are caused almost exclusively by the CCR5-tropic HIV-1 strains, our results suggest that prior immunization with vaccinia virus might provide an individual with some degree of protection to subsequent HIV infection and/or progression. The duration of such protection remains to be determined. A differential elaboration of MIP-1α, MIP-1β and RANTES between vaccinated and unvaccinated subjects, following infection, does not appear to be a mechanism in the noted protection.</p

Mass and angular-momentum inequalities for axi-symmetric initial data sets I. Positivity of mass

We extend the validity of Brill's axisymmetric positive energy theorem to all asymptotically flat initial data sets with positive scalar curvature on simply connected manifolds.Comment: 33 pages in A

Self-determined self-other overlap: Interacting effects on partners’ perceptions of support and well-being in close relationships

Self-other overlap, an important dimension of interpersonal closeness, is linked to positive interpersonal and well-being outcomes in relationships with romantic partners and friends. Three studies applied principles from self-determination theory to examine whether individual differences in self-determined motivation moderate the effects of higher self-other overlap on partner outcomes. Studies were crosssectional and longitudinal, and examined personality and relationship specific self-determination in friends (Study 1) and romantic partners (all studies); all were comprised of dyads to examine partner effects. Results suggested that as self-determined individuals reported greater self-other overlap, their partners also reported receiving more positive motivational support as well as enhanced commitment. On the other hand, when individuals were low in self-determination, partners did not benefit from greater self-other overlap

Effective antiprotease-antibiotic treatment of experimental anthrax

BACKGROUND: Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our understanding of anthrax molecular pathology and the most prominent clinical features of the infectious process we undertook bioinformatic and experimental analyses of potential proteolytic virulence factors of B. anthracis distinct from lethal toxin. METHODS: Secreted proteins (other than lethal and edema toxins) produced by B. anthracis were tested for tissue-damaging activity and toxicity in mice. Chemical protease inhibitors and rabbit immune sera raised against B. anthracis proteases were used to treat mice challenged with B. anthracis (Sterne) spores. RESULTS: B. anthracis strain delta Ames (pXO1(-), pXO2(-)) producing no lethal and edema toxins secrets a number of metalloprotease virulence factors upon cultivation under aerobic conditions, including those with hemorrhagic, caseinolytic and collagenolytic activities, belonging to M4 and M9 thermolysin and bacterial collagenase families, respectively. These factors are directly toxic to DBA/2 mice upon intratracheal administration at 0.5 mg/kg and higher doses. Chemical protease inhibitors (phosphoramidon and 1, 10-phenanthroline), as well as immune sera against M4 and M9 proteases of B. anthracis, were used to treat mice challenged with B. anthracis (Sterne) spores. These substances demonstrate a substantial protective efficacy in combination with ciprofloxacin therapy initiated as late as 48 h post spore challenge, compared to the antibiotic alone. CONCLUSION: Secreted proteolytic enzymes are important pathogenic factors of B. anthrasis, which can be considered as effective therapeutic targets in the development of anthrax treatment and prophylactic approaches complementing anti-lethal toxin therapy

Rotational Cooling of Polar Molecules by Stark-tuned Cavity Resonance

A general scheme for rotational cooling of diatomic heteronuclear molecules is proposed. It uses a superconducting microwave cavity to enhance the spontaneous decay via Purcell effect. Rotational cooling can be induced by sequentially tuning each rotational transition to cavity resonance, starting from the highest transition level to the lowest using an electric field. Electrostatic multipoles can be used to provide large confinement volume with essentially homogeneous background electric field.Comment: 10 pages, 6 figure

The effect of iliac crest autograft on the outcome of fusion in the setting of degenerative spondylolisthesis: a subgroup analysis of the Spine Patient Outcomes Research Trial (SPORT).

BACKGROUND: There is considerable controversy about the long-term morbidity associated with the use of posterior autologous iliac crest bone graft for lumbar spine fusion procedures compared with the use of bone-graft substitutes. The hypothesis of this study was that there is no long-term difference in outcome for patients who had posterior lumbar fusion with or without iliac crest autograft. METHODS: The study population includes patients enrolled in the degenerative spondylolisthesis cohort of the Spine Patient Outcomes Research Trial who underwent lumbar spinal fusion. Patients were divided according to whether they had or had not received posterior autologous iliac crest bone graft. RESULTS: There were 108 patients who had fusion with iliac crest autograft and 246 who had fusion without iliac crest autograft. There were no baseline differences between groups in demographic characteristics, comorbidities, or baseline clinical scores. At baseline, the group that received iliac crest bone graft had an increased percentage of patients who had multilevel fusions (32% versus 21%; p=0.033) and L5-S1 surgery (37% versus 26%; p=0.031) compared with the group without iliac crest autograft. Operative time was higher in the iliac crest bone-graft group (233.4 versus 200.9 minutes; p CONCLUSIONS: The outcome scores associated with the use of posterior iliac crest bone graft for lumbar spinal fusion were not significantly lower than those after fusion without iliac crest autograft. Conversely, iliac crest bone-grafting was not associated with an increase in the complication rates or rates of reoperation. On the basis of these results, surgeons may choose to use iliac crest bone graft on a case-by-case basis for lumbar spinal fusion

Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

Background: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort