Acceptance and timeliness of post-exposure vaccination against mpox in high-risk contacts, Amsterdam, the Netherlands, May-July 2022.

BACKGROUND: May 2022, several countries reported mpox outbreaks among men-who-have-sex-with-men. In the Netherlands, high-risk contacts were offered the third-generation smallpox vaccine as post-exposure-prophylaxis (PEP) within 4 but maximum 14 days after exposure. We investigated their PEP acceptance, timeliness of uptake and development of mpox for the region of the Public Health Service (PHS) Amsterdam. METHODS: High-risk contacts identified during 20 May-22 July 2022 were included. Contacts were followed-up 21 days after exposure and classified as: no patient (no mpox symptoms or orthopoxvirus PCR-negative) or mpox patient (clinically suspected mpox or orthopoxvirus PCR-positive). We calculated time intervals between date of last exposure and first PHS consultation, PEP administration, and symptom onset. RESULTS: Two-hundred-ninety contacts were at high-risk of mpox predominantly due to sexual and/or direct skin-skin contact (212/290, 73 %). First PHS consultation was a median of 5 (IQR 3, 7) days after exposure, at which point 26/290 (9 %) contacts were ineligible for PEP. 84 % (223/264) of contacts eligible for PEP, received PEP within a median of 6 (IQR 3, 8) days after exposure. Of 282 contacts (missing outcome n = 8) 38 (14 %) developed mpox a median of 7 (IQR 5, 12) days after exposure, of whom 50 % (19/38) developed mpox before their first PHS consultation. Among contacts eligible for PEP, 2/38 (5 %) unvaccinated and 16/218 (7 %) vaccinated contact developed mpox. CONCLUSIONS: PEP acceptance among contacts of mpox patients was high. However, PEP timeliness was inadequate. Half of contacts received PEP 6 or more days after exposure, and half of contacts who developed mpox had an onset prior to their first PHS consultation. Estimating PEP vaccine effectiveness is problematic due to the timeliness of PEP and the time it takes to generate vaccine-induced immunity. It is important to assess how PEP timeliness may improve and to promote pre-exposure vaccination to control mpox outbreaks.

Current Female Firefighters' Perceptions, Attitudes, and Experiences with Injury.

Research presented here examines how the demands of fire fighting uniquely affect women. A national sample of 73 female firefighters and fire-service leaders participated in focus groups and key informant interviews. Participants were asked about perceived threats to safety and standard operating procedures (SOPs) that lead to injury regarding gender differences. A thematic qualitative analysis was conducted and the following six themes were identified: (1) impact of working in a male-dominated field, (2) harassment, (3) similar rates/types of injury, (4) inadequate training, (5) ill-fitting gear, and (6) functional techniques/endurance. Both chronic and acute injuries/causes were discussed. Future direction will require diversity education and new training methodologies for the fire service.

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles.

Leishmaniasis is a disease caused by parasites of Leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. The current treatments for visceral leishmaniasis (VL), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. One way to limit emergence of resistant pathogens is through the use of host-mediated therapeutics. The host-mediated therapeutic AR-12, which is FDA IND-approved for cancer treatment, has shown activity against a broad spectrum of intracellular pathogens; however, due to hydrophobicity and toxicity, it is difficult to reach therapeutic doses. We have formulated AR-12 into microparticles (AR-12/MPs) using the novel biodegradable polymer acetalated dextran (Ace-DEX) and used this formulation for the systemic treatment of VL. Treatment with AR-12/MPs significantly reduced liver, spleen, and bone marrow parasite loads in infected mice, while combinatorial therapies with amphotericin B had an even more significant effect. Overall, AR-12/MPs offer a unique, host-mediated therapy that could significantly reduce the emergence of drug resistance in the treatment of VL.

Evaluation of a biodegradable microparticulate polymer as a carrier for Burkholderia pseudomallei subunit vaccines in a mouse model of melioidosis.

Melioidosis, a potentially lethal disease of humans and animals, is caused by the soil-dwelling bacterium Burkholderia pseudomallei. Due to B. pseudomallei's classification as a Tier 1 Select Agent, there is substantial interest in the development of an effective vaccine. Yet, despite decades of research, no effective target, adjuvant or delivery vehicle capable of inducing protective immunity against B. pseudomallei infection has been identified. We propose a microparticulate delivery vehicle comprised of the novel polymer acetalated dextran (Ac-DEX). Ac-DEX is an acid-sensitive biodegradable carrier that can be fabricated into microparticles (MPs) that are relatively stable at pH 7.4, but rapidly degrade after phagocytosis by antigen presenting cells where the pH can drop to 5.0. As compared to other biomaterials, this acid sensitivity has been shown to enhance cross presentation of subunit antigens. To evaluate this platform as a delivery system for a melioidosis vaccine, BALB/c mice were vaccinated with Ac-DEX MPs separately encapsulating B. pseudomallei whole cell lysate and the toll-like receptor (TLR) 7/8 agonist resiquimod. This vaccine elicited a robust antibody response that included both Th1 and Th2 immunity. Following lethal intraperitoneal challenge with B. pseudomallei 1026b, vaccinated mice demonstrated a significant delay to time of death compared to untreated mice. The formulation, however, demonstrated incomplete protection indicating that lysate protein offers limited value as an antigen. Nevertheless, our Ac-DEX MPs may offer an effective delivery vehicle for a subunit B. psuedomallei vaccine.

A selective review of prenatal exercise guidelines since the 1950s until present: Written for women, health care professionals, and female athletes.

BACKGROUND: Traditional society values have long-held the notion that the pregnant woman is construed as a risk to her growing fetus and is solely responsible for controlling this risk to ensure a healthy pregnancy. It is hard to ignore the participation of pregnant women in sport and exercise today, especially in high-level sports and popular fitness programs such as CrossFit™. This challenges both traditional and modern prenatal exercise guidelines from health care professionals and governing health agencies. The guidelines and perceived limitations of prenatal exercise have drastically evolved since the 1950s. AIM: The goal of this paper is to bring awareness to the idea that much of the information regarding exercise safety during pregnancy is hypersensitive and dated, and the earlier guidelines had no scientific rigor. Research is needed on the upper limits of exercise intensity and exercise frequency, as well as their potential risks (if any) on the woman or fetus. DISCUSSION: Pregnant women are physically capable of much more than what was once thought. There is still disagreement about the types of exercise deemed appropriate, the stage at which exercise should begin and cease, the frequency of exercise sessions, as well as the optimal level of intensity during prenatal exercise. CONCLUSION: Research is needed to determine the upper limits of exercise frequency and intensity for pregnant women who are already trained. Healthy women and female athletes can usually maintain their regular training regime once they become pregnant.

Magnetic resonance imaging of iron oxide labelled stem cells: applications to tissue engineering based regeneration of the intervertebral disc.

Minimally-invasive monitoring of regeneration in diseased tissue is an important aspect of stem cell therapy. Magnetic resonance imaging (MRI) based tracking of cells labelled with ferumoxides has the potential for non-invasive in vivo detection and longitudinal assessment of implanted cells. Cells labelled with ferumoxides appear as hypointense regions on MR images and thus can be distinguished from the surroundings. Application of this methodology to intervertebral disc degeneration (IVD), and detection of labelled cells implanted into the disc for tissue regeneration was examined. Mesenchymal stem cells labelled with a ferumoxide contrast agent were imaged in vitro to quantitatively characterize the signal intensity loss using MRI relaxation parameters (T1, T2, and T2*). To determine whether labelled cells could be detected within scaffolds suitable for implantation, labelled cells were seeded within both natural and synthetic polymers and imaged using MRI. Labelled cells were loaded within poly(ethylene glycol) hydrogels and imaged in vitro using both MRI and confocal microscopy. Labelled cells were also loaded into fibrin gels, and detected ex vivo within rat IVDs using MRI. Lastly, the effect of ferumoxide labelling on cell viability was investigated. Quantitatively, labelled cells demonstrate the greatest signal intensity loss and contrast on T2*-weighted images. Labelled cells can be detected in both synthetic and natural polymers, and can be distinguished from the native tissue environment of the rat IVD. Finally, labelling does not significantly impair cell viability. Consequently, this technique shows promise as a potential method for in vivo longitudinal tracking of stem cell based regeneration of the IVD.