Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

<p>Abstract</p> <p>Background</p> <p>Bovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays.</p> <p>Results</p> <p>The cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action.</p> <p>HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-β-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV-1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours.</p> <p>Conclusions</p> <p>bDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours.</p> <p>bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals.</p

CC8 MRSA Strains Harboring SCCmec Type IVc are Predominant in Colombian Hospitals

BACKGROUND: Recent reports highlight the incursion of community-associated MRSA within healthcare settings. However, knowledge of this phenomenon remains limited in Latin America. The aim of this study was to evaluate the molecular epidemiology of MRSA in three tertiary-care hospitals in Medellín, Colombia. METHODS: An observational cross-sectional study was conducted from 2008-2010. MRSA infections were classified as either community-associated (CA-MRSA) or healthcare-associated (HA-MRSA), with HA-MRSA further classified as hospital-onset (HAHO-MRSA) or community-onset (HACO-MRSA) according to standard epidemiological definitions established by the U.S. Centers for Disease Control and Prevention (CDC). Genotypic analysis included SCCmec typing, spa typing, PFGE and MLST. RESULTS: Out of 538 total MRSA isolates, 68 (12.6%) were defined as CA-MRSA, 243 (45.2%) as HACO-MRSA and 227 (42.2%) as HAHO-MRSA. The majority harbored SCCmec type IVc (306, 58.7%), followed by SCCmec type I (174, 33.4%). The prevalence of type IVc among CA-, HACO- and HAHO-MRSA isolates was 92.4%, 65.1% and 43.6%, respectively. From 2008 to 2010, the prevalence of type IVc-bearing strains increased significantly, from 50.0% to 68.2% (p = 0.004). Strains harboring SCCmec IVc were mainly associated with spa types t1610, t008 and t024 (MLST clonal complex 8), while PFGE confirmed that the t008 and t1610 strains were closely related to the USA300-0114 CA-MRSA clone. Notably, strains belonging to these three spa types exhibited high levels of tetracycline resistance (45.9%). CONCLUSION: CC8 MRSA strains harboring SCCmec type IVc are becoming predominant in Medellín hospitals, displacing previously reported CC5 HA-MRSA clones. Based on shared characteristics including SCCmec IVc, absence of the ACME element and tetracycline resistance, the USA300-related isolates in this study are most likely related to USA300-LV, the recently-described 'Latin American variant' of USA300

Cost-effectiveness of human papillomavirus vaccination for prevention of cervical cancer in Taiwan

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) infection has been shown to be a major risk factor for cervical cancer. Vaccines against HPV-16 and HPV-18 are highly effective in preventing type-specific HPV infections and related cervical lesions. There is, however, limited data available describing the health and economic impacts of HPV vaccination in Taiwan. The objective of this study was to assess the cost-effectiveness of prophylactic HPV vaccination for the prevention of cervical cancer in Taiwan.</p> <p>Methods</p> <p>We developed a Markov model to compare the health and economic outcomes of vaccinating preadolescent girls (at the age of 12 years) for the prevention of cervical cancer with current practice, including cervical cytological screening. Data were synthesized from published papers or reports, and whenever possible, those specific to Taiwan were used. Sensitivity analyses were performed to account for important uncertainties and different vaccination scenarios.</p> <p>Results</p> <p>Under the assumption that the HPV vaccine could provide lifelong protection, the massive vaccination among preadolescent girls in Taiwan would lead to reduction in 73.3% of the total incident cervical cancer cases and would result in a life expectancy gain of 4.9 days or 8.7 quality-adjusted life days at a cost of US$324 as compared to the current practice. The incremental cost-effectiveness ratio (ICER) was US$23,939 per life year gained or US$13,674 per quality-adjusted life year (QALY) gained given the discount rate of 3$30,000 per QALY under most conditions, even when vaccine efficacy was suboptimal or when vaccine-induced immunity required booster shots every 13 years.</p> <p>Conclusions</p> <p>Although gains in life expectancy may be modest at the individual level, the results indicate that prophylactic HPV vaccination of preadolescent girls in Taiwan would result in substantial population benefits with a favorable cost-effectiveness ratio. Nevertheless, we should not overlook the urgency to improve the compliance rate of cervical screening, particularly for older individuals.</p

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Genome-Wide Analysis of Gene Expression in Primate Taste Buds Reveals Links to Diverse Processes

Efforts to unravel the mechanisms underlying taste sensation (gustation) have largely focused on rodents. Here we present the first comprehensive characterization of gene expression in primate taste buds. Our findings reveal unique new insights into the biology of taste buds. We generated a taste bud gene expression database using laser capture microdissection (LCM) procured fungiform (FG) and circumvallate (CV) taste buds from primates. We also used LCM to collect the top and bottom portions of CV taste buds. Affymetrix genome wide arrays were used to analyze gene expression in all samples. Known taste receptors are preferentially expressed in the top portion of taste buds. Genes associated with the cell cycle and stem cells are preferentially expressed in the bottom portion of taste buds, suggesting that precursor cells are located there. Several chemokines including CXCL14 and CXCL8 are among the highest expressed genes in taste buds, indicating that immune system related processes are active in taste buds. Several genes expressed specifically in endocrine glands including growth hormone releasing hormone and its receptor are also strongly expressed in taste buds, suggesting a link between metabolism and taste. Cell type-specific expression of transcription factors and signaling molecules involved in cell fate, including KIT, reveals the taste bud as an active site of cell regeneration, differentiation, and development. IKBKAP, a gene mutated in familial dysautonomia, a disease that results in loss of taste buds, is expressed in taste cells that communicate with afferent nerve fibers via synaptic transmission. This database highlights the power of LCM coupled with transcriptional profiling to dissect the molecular composition of normal tissues, represents the most comprehensive molecular analysis of primate taste buds to date, and provides a foundation for further studies in diverse aspects of taste biology

Precision measurement of CP\it{CP} violation in the penguin-mediated decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi

A flavor-tagged time-dependent angular analysis of the decay $B_s^{0}\rightarrow\phi\phi$ is performed using $pp$ collision data collected by the LHCb experiment at % at $\sqrt{s}=13$ TeV, the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The $\it{CP}$-violating phase and direct $\it{CP}$-violation parameter are measured to be $\phi_{s\bar{s}s} = -0.042 \pm 0.075 \pm 0.009$ rad and $|\lambda|=1.004\pm 0.030 \pm 0.009$, respectively, assuming the same values for all polarization states of the $\phi\phi$ system. In these results, the first uncertainties are statistical and the second systematic. These parameters are also determined separately for each polarization state, showing no evidence for polarization dependence. The results are combined with previous LHCb measurements using $pp$ collisions at center-of-mass energies of 7 and 8 TeV, yielding $\phi_{s\bar{s}s} = -0.074 \pm 0.069$ rad and $|lambda|=1.009 \pm 0.030$. This is the most precise study of time-dependent $\it{CP}$ violation in a penguin-dominated $B$ meson decay. The results are consistent with $\it{CP}$ symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb public pages

Measurement of the Λb0→Λ(1520)μ+μ−\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-} differential branching fraction

The branching fraction of the rare decay $\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-}$ is measured for the first time, in the squared dimuon mass intervals, $q^2$, excluding the $J/\psi$ and $\psi(2S)$ regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\ \mathrm{fb}^{-1}$. The result in the highest$q^{2}$interval,$q^{2} >15.0\ \mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb public pages