Cost-Effectiveness of Newborn Circumcision in Reducing Lifetime HIV Risk among U.S. Males

BACKGROUND: HIV incidence was substantially lower among circumcised versus uncircumcised heterosexual African men in three clinical trials. Based on those findings, we modeled the potential effect of newborn male circumcision on a U.S. male's lifetime risk of HIV, including associated costs and quality-adjusted life-years saved. METHODOLOGY/PRINCIPAL FINDINGS: Given published estimates of U.S. males' lifetime HIV risk, we calculated the fraction of lifetime risk attributable to heterosexual behavior from 2005-2006 HIV surveillance data. We assumed 60% efficacy of circumcision in reducing heterosexually-acquired HIV over a lifetime, and varied efficacy in sensitivity analyses. We calculated differences in lifetime HIV risk, expected HIV treatment costs and quality-adjusted life years (QALYs) among circumcised versus uncircumcised males. The main outcome measure was cost per HIV-related QALY saved. Circumcision reduced the lifetime HIV risk among all males by 15.7% in the base case analysis, ranging from 7.9% for white males to 20.9% for black males. Newborn circumcision was a cost-saving HIV prevention intervention for all, black and Hispanic males. The net cost of newborn circumcision per QALY saved was $87,792 for white males. Results were most sensitive to the discount rate, and circumcision efficacy and cost. CONCLUSIONS/SIGNIFICANCE: Newborn circumcision resulted in lower expected HIV-related treatment costs and a slight increase in QALYs. It reduced the 1.87% lifetime risk of HIV among all males by about 16%. The effect varied substantially by race and ethnicity. Racial and ethnic groups who could benefit the most from circumcision may have least access to it due to insurance coverage and state Medicaid policies, and these financial barriers should be addressed. More data on the long-term protective effect of circumcision on heterosexual males as well as on its efficacy in preventing HIV among MSM would be useful

The Protective Effects of Melittin on Propionibacterium acnes–Induced Inflammatory Responses In Vitro and In Vivo

Melittin is the main component in the venom of the honey bee (Apis mellifera). It has multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-inflammatory mechanisms of melittin have not been elucidated in Propionibactierium acnes (P. acnes)–induced keratinocyte or inflammatory skin disease animal models. In this study, we examined the effects of melittin on the production of inflammatory cytokines in heat-killed P. acnes–induced HaCaT cells. Heat-killed P. acnes–treated keratinocytes increased the expression of pro-inflammatory cytokines and Toll-like receptor 2. However, melittin treatment significantly suppressed the expression of these cytokines through regulation of the NF-κB and MAPK signaling pathways. Subsequently, the living P. acnes (1 × 107 CFU) were intradermally injected into the ear of mice. Living P. acnes–injected ears showed cutaneous erythema, swelling, and granulomatous response at 24 hours after injection. However, melittin-treated ears showed markedly reduced swelling and granulomatous responses compared with ears injected with only living P. acnes. These results demonstrate the feasibility of applying melittin for the prevention of inflammatory skin diseases induced by P. acnes

Role of Exonic Variation in Chemokine Receptor Genes on AIDS: CCRL2 F167Y Association with Pneumocystis Pneumonia

Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 andCCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28–6.31) among four major AIDS–defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

The Transcriptome of Lutzomyia longipalpis (Diptera: Psychodidae) Male Reproductive Organs

BACKGROUND: It has been suggested that genes involved in the reproductive biology of insect disease vectors are potential targets for future alternative methods of control. Little is known about the molecular biology of reproduction in phlebotomine sand flies and there is no information available concerning genes that are expressed in male reproductive organs of Lutzomyia longipalpis, the main vector of American visceral leishmaniasis and a species complex. METHODS/PRINCIPAL FINDINGS: We generated 2678 high quality ESTs ("Expressed Sequence Tags") of L. longipalpis male reproductive organs that were grouped in 1391 non-redundant sequences (1136 singlets and 255 clusters). BLAST analysis revealed that only 57% of these sequences share similarity with a L. longipalpis female EST database. Although no more than 36% of the non-redundant sequences showed similarity to protein sequences deposited in databases, more than half of them presented the best-match hits with mosquito genes. Gene ontology analysis identified subsets of genes involved in biological processes such as protein biosynthesis and DNA replication, which are probably associated with spermatogenesis. A number of non-redundant sequences were also identified as putative male reproductive gland proteins (mRGPs), also known as male accessory gland protein genes (Acps). CONCLUSIONS: The transcriptome analysis of L. longipalpis male reproductive organs is one step further in the study of the molecular basis of the reproductive biology of this important species complex. It has allowed the identification of genes potentially involved in spermatogenesis as well as putative mRGPs sequences, which have been studied in many insect species because of their effects on female post-mating behavior and physiology and their potential role in sexual selection and speciation. These data open a number of new avenues for further research in the molecular and evolutionary reproductive biology of sand flies

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389