Oral Immunization with a Live Coxsackievirus/HIV Recombinant Induces Gag p24-Specific T Cell Responses

The development of an HIV/AIDS vaccine has proven to be elusive. Because human vaccine trials have not yet demonstrated efficacy, new vaccine strategies are needed for the HIV vaccine pipeline. We have been developing a new HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vector. Enteroviruses are ideal candidates for development as a vaccine vector for oral delivery, because these viruses normally enter the body via the oral route and survive the acidic environment of the stomach.We constructed a live coxsackievirus B4 recombinant, CVB4/p24(73(3)), that expresses seventy-three amino acids of the gag p24 sequence (HXB2) and assessed T cell responses after immunization of mice. The CVB4 recombinant was physically stable, replication-competent, and genetically stable. Oral or intraperitoneal immunization with the recombinant resulted in strong systemic gag p24-specific T cell responses as determined by the IFN-gamma ELISPOT assay and by multiparameter flow cytometry. Oral immunization with CVB4/p24(73(3)) resulted in a short-lived, localized infection of the gut without systemic spread. Because coxsackieviruses are ubiquitous in the human population, we also evaluated whether the recombinant was able to induce gag p24-specific T cell responses in mice pre-immunized with the CVB4 vector. We showed that oral immunization with CVB4/p24(73(3)) induced gag p24-specific immune responses in vector-immune mice.The CVB4/p24(73(3)) recombinant retained the physical and biological characteristics of the parental CVB4 vector. Oral immunization with the CVB4 recombinant was safe and resulted in the induction of systemic HIV-specific T cell responses. Furthermore, pre-existing vector immunity did not preclude the development of gag p24-specific T cell responses. As the search continues for new vaccine strategies, the present study suggests that live CVB4/HIV recombinants are potential new vaccine candidates for HIV

A comparison of cryopreservation methods: Slow-cooling vs. rapid-cooling based on cell viability, oxidative stress, apoptosis, and CD34+ enumeration of human umbilical cord blood mononucleated cells

<p>Abstract</p> <p>Background</p> <p>The finding of human umbilical cord blood as one of the most likely sources of hematopoietic stem cells offers a less invasive alternative for the need of hematopoietic stem cell transplantation. Due to the once-in-a-life time chance of collecting it, an optimum cryopreservation method that can preserve the life and function of the cells contained is critically needed.</p> <p>Methods</p> <p>Until now, slow-cooling has been the routine method of cryopreservation; however, rapid-cooling offers a simple, efficient, and harmless method for preserving the life and function of the desired cells. Therefore, this study was conducted to compare the effectiveness of slow- and rapid-cooling to preserve umbilical cord blood of mononucleated cells suspected of containing hematopoietic stem cells. The parameters used in this study were differences in cell viability, malondialdehyde content, and apoptosis level. The identification of hematopoietic stem cells themselves was carried out by enumerating CD34⁺in a flow cytometer.</p> <p>Results</p> <p>Our results showed that mononucleated cell viability after rapid-cooling (91.9%) was significantly higher than that after slow-cooling (75.5%), with a <it>p </it>value = 0.003. Interestingly, the malondialdehyde level in the mononucleated cell population after rapid-cooling (56.45 μM) was also significantly higher than that after slow-cooling (33.25 μM), with a <it>p </it>value < 0.001. The apoptosis level in rapid-cooling population (5.18%) was not significantly different from that of the mononucleated cell population that underwent slow-cooling (3.81%), with a <it>p </it>value = 0.138. However, CD34⁺enumeration was much higher in the population that underwent slow-cooling (23.32 cell/μl) than in the one that underwent rapid-cooling (2.47 cell/μl), with a <it>p </it>value = 0.001.</p> <p>Conclusions</p> <p>Rapid-cooling is a potential cryopreservation method to be used to preserve the umbilical cord blood of mononucleated cells, although further optimization of the number of CD34⁺cells after rapid-cooling is critically needed.</p

Using Magnetically Responsive Tea Waste to Remove Lead in Waters under Environmentally Relevant Conditions

We report the use of a simple yet highly effective magnetite-waste tea composite to remove lead(II) (Pb[superscript 2+]) ions from water. Magnetite-waste tea composites were dispersed in four different types of water–deionized (DI), artificial rainwater, artificial groundwater and artificial freshwater–that mimic actual environmental conditions. The water samples had varying initial concentrations (0.16–5.55 ppm) of Pb[superscript 2+] ions and were mixed with the magnetite-waste tea composite for at least 24 hours to allow adsorption of the Pb[superscript 2+] ions to reach equilibrium. The magnetite-waste tea composites were stable in all the water samples for at least 3 months and could be easily removed from the aqueous media via the use of permanent magnets. We detected no significant leaching of iron (Fe) ions into the water from the magnetite-waste tea composites. The percentage of Pb adsorbed onto the magnetite-waste tea composite ranged from ~70% to 100%; the composites were as effective as activated carbon (AC) in removing the Pb[superscript 2+] ions from water, depending on the initial Pb concentration. Our prepared magnetite-waste tea composites show promise as a green, inexpensive and highly effective sorbent for removal of Pb in water under environmentally realistic conditions.SUTD-MIT International Design Center (Research Grant IDG11200105/IDD11200109)Singapore-MIT Allianc

Reliability of self-reported health risk factors and chronic conditions questions collected using the telephone in South Australia, Australia

Extent: 10p.Background: Accurate monitoring of health conditions and behaviours, and health service usage in the population, using an effective and economical method is important for planning and evaluation. This study examines the reliability of questions asked in a telephone survey by conducting a test/retest analysis of a range of questions covering demographic variables, health risk factors and self-reported chronic conditions among people aged 16 years and over. Methods: A Computer Assisted Telephone Interviewing (CATI) survey on health issues of South Australians was re-administered to a random sub-sample of 154 respondents between 13-35 days (mean 17) after the original survey. Reliability between questions was assessed using Cohen’s kappa and intraclass correlation coefficients. Results: Demographic questions (age, gender, number of adults and children in the household, country of birth) showed extremely high reliability (0.97 to 1.00). Health service use (ICC = 0.90 95% CI 0.86-0.93) and overall health status (Kappa = 0.60 95% CI 0.46-0.75) displayed moderate agreement. Questions relating to self-reported risk factors such as smoking (Kappa = 0.81 95% CI 0.72-0.89) and alcohol drinking (ICC 0.75 = 95% CI 0.63-0.83) behaviour showed good to excellent agreement, while questions relating to self-reported risk factors such as time spent walking for physical activity (ICC 0.47 = 95% CI 0.27-0.61), fruit (Kappaw = 0.60 95% CI 0.45-0.76) and vegetable consumption (Kappaw = 0.50 95% CI 0.32-0.69) showed only moderate agreement. Self-reported chronic conditions displayed substantial to almost perfect agreement (0.72 to 1.00) with the exception of moderate agreement for heart disease (Kappa = 0.82 95% CI 0.57-0.99). Conclusion: These results show the questions assessed to be reliable in South Australia for estimating health conditions and monitoring health related behaviours using a CATI survey.Eleonora Dal Grande, Simon Fullerton and Anne W Taylo

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta