Considerations for use of Ebola vaccine during an emergency response.

Vaccination against Ebola virus disease is a tool that may limit disease transmission and deaths in future outbreaks, integrated within traditional Ebola outbreak prevention and control measures. Although a licensed Ebolavirus vaccine (EV) is not yet available, the 2014-2016 West African Ebola outbreak has accelerated EV clinical trials and given public health authorities in Guinea, Liberia, and Sierra Leone experience with implementation of emergency ring vaccination. As evidence supporting the use of EV during an outbreak response has become available, public health authorities in at-risk countries are considering how to integrate EV into future emergency Ebola responses and for prevention in high-risk groups, such as healthcare workers and frontline workers (HCW/FLWs), even before an EV is licensed. This review provides an overview of Ebola epidemiology, immunology, and evidence to inform regional and country-level decisions regarding EV delivery during an emergency response and to at-risk populations before a licensed vaccine is available and beyond. Countries or regions planning to use EV will need to assess factors such as the likelihood of a future Ebolavirus outbreak, the most likely species to cause an outbreak, the availability of a safe and effective EV (unlicensed or licensed) for the affected population, capacity to implement Ebola vaccination in conjunction with standard Ebola outbreak control measures, and availability of minimum essential resources and regulatory requirements to implement emergency Ebola vaccination. Potential emergency vaccination strategies for consideration include ring or geographically targeted community vaccination, HCW/FLW vaccination, and mass vaccination. The development of guidelines and protocols for Ebola vaccination will help ensure that activities are standardized, evidence-based, and well-coordinated with overall Ebola outbreak response efforts in the future.

Isotopic Dependence of the Hydrogen-Transfer-Triggered Methyl-Group Rotation in Deuterated 5-Methyltropolone.

We present here the first experimental study of the microwave spectrum of deuterated 5-methyltropolone, a molecule which exhibits two large-amplitude motions: an intramolecular hydrogen transfer (deuterium transfer in the current case of deuterated 5-methyltropolone) and a methyl torsion. The main goal of this study was to get information on the isotopic dependence of the main tunneling parameters of 5-methyltropolone in the framework of the two dimensional tunneling formalism, which previously has shown some counterintuitive results for isotopic dependence of tunneling parameters in 2-methylmalonaldehyde. Measurements were carried out by Fourier-transform microwave spectroscopy in the 9 GHz to 26 GHz frequency range. Theoretical analysis was carried out using a tunneling-rotational Hamiltonian based on a G12 m extended-group-theory formalism. Our global fit of 384 transitions to 17 molecular parameters gave a weighted root-mean-square deviation of 0.8. The current study on the isotopic dependence of the main tunneling parameters in 5-methyltropolone supports the assumption of possible "leakage" between tunneling parameters in the two-dimensional tunneling formalism in use.

Timing of HPV vaccine intervals among United States teens with consideration to the current ACIP schedule and the WHO 2-dose schedule.

The current recommendation for human papillomavirus (HPV) vaccination in the United States is for 3 doses to be administered over a 6 month period. In April 2014, the World Health Organization (WHO) recommended adoption of a 2-dose schedule, with doses spaced a minimum of 6 months apart, for teens who begin the series before age 15. We analyzed data from the 2013 National Immunization Survey-Teen to examine the timing of second and third dose receipt among US adolescents. All analyses were restricted to adolescents age 13-17 y who had adequate provider data. The Wilcoxon-Mann-Whitney test measured differences in time to receive vaccine doses among demographic and socioeconomic groups. Logistic regression identified socioeconomic characteristics associated with receiving the second dose of HPV vaccine at least 6 months after the first dose. The median time for teens to receive the second dose of HPV vaccine was 2.6 months after the first dose, and the median time to receive the third dose was 4.9 months after the second dose. Minority teens and teens living below the poverty level took significantly longer to receive doses. Among teens that initiated the HPV vaccine series before age 15 y, 28.6% received the second dose at least 6 months after the first dose. If these teens, who met the WHO criteria for up-to-date HPV vaccination, were classified as having completed the vaccination series, overall coverage in the US would increase 3.9 percentage points, with African American and Hispanic teens having the greatest increases in coverage.

Neutral sphingomyelinase 2 (nSMase2) is the primary neutral sphingomyelinase isoform activated by tumour necrosis factor-α in MCF-7 cells.

Activation of N-SMase (neutral sphingomyelinase) is an established part of the response of cytokines such as TNF (tumour necrosis factor)-α. However, it remains unclear which of the currently cloned N-SMase isoforms (nSMase1, nSMase2 and nSMase3) are responsible for this activity. In MCF-7 cells, we found that TNF-α induces late, but not early, increases in N-SMase activity, and that nSMase2 is the primary isoform activated, most likely through post-transcriptional mechanisms. Surprisingly, overexpression of tagged or untagged nSMase3 in multiple cell lines had no significant effect on in vitro N-SMase activity. Moreover, only overexpression of nSMase2, but not nSMase1 or nSMase3, had significant effects on cellular sphingolipid levels, increasing ceramide and decreasing sphingomyelin. Additionally, only siRNA (small interfering RNA) knockdown of nSMase1 significantly decreased basal in vitro N-SMase activity of MCF-7 cells, whereas nSMase2 but not nSMase3 siRNA inhibited TNF-α-induced activity. Taken together, these results identify nSMase2 as the major TNF-α-responsive N-SMase in MCF-7 cells. Moreover, the results suggest that nSMase3 may not possess in vitro N-SMase activity and does not affect cellular sphingolipid levels in the cell lines evaluated. On the other hand, nSMase1 contributes to in vitro N-SMase activity, but does not affect cellular sphingolipids much.

A microwave study of hydrogen-transfer-triggered methyl-group rotation in 5-methyltropolone.

We present here the first experimental and theoretical study of the microwave spectrum of 5-methyltropolone, which can be visualized as a seven-membered "aromatic" carbon ring with a five-membered hydrogen-bonded cyclic structure at the top and a methyl group at the bottom. The molecule is known from earlier studies in the literature to exhibit two large-amplitude motions, an intramolecular hydrogen transfer and a methyl torsion. The former motion is particularly interesting because transfer of the hydrogen atom from the hydroxyl to the carbonyl group induces a tautomerization in the molecule, which then triggers a 60° internal rotation of the methyl group. Measurements were carried out by Fourier-transform microwave spectroscopy in the 8-24 GHz frequency range. Theoretical analysis was carried out using a tunneling-rotational Hamiltonian based on a G(12)(m) extended-group-theory formalism. Our global fit of 1015 transitions to 20 molecular parameters gave a root-mean-square deviation of 1.5 kHz. The tunneling splitting of the two J=0 levels arising from a hypothetical pure hydrogen-transfer motion is calculated to be 1310 MHz. The tunneling splitting of the two J=0 levels arising from a hypothetical pure methyl top internal-rotation motion is calculated to be 885 MHz. We have also carried out ab initio calculations, which support the structural parameters determined from our spectroscopic analysis and give estimates of the barriers to the two large-amplitude motions.