Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart.

Adding a cationic helper lipid to a lipid nanoparticle (LNP) can increase lung delivery and decrease liver delivery. However, it remains unclear whether charge-dependent tropism is universal or, alternatively, whether it depends on the component that is charged. Here, we report evidence that cationic cholesterol-dependent tropism can differ from cationic helper lipid-dependent tropism. By testing how 196 LNPs delivered mRNA to 22 cell types, we found that charged cholesterols led to a different lung:liver delivery ratio than charged helper lipids. We also found that combining cationic cholesterol with a cationic helper lipid led to mRNA delivery in the heart as well as several lung cell types, including stem cell-like populations. These data highlight the utility of exploring charge-dependent LNP tropism.

The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli. RESULTS: No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli. CONCLUSION: These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.

Postcrisis Follow-Up and Linkage to Community Services.

During the postcrisis period, many individuals struggle to transition to available care, often falling through the cracks. This article discusses effective postcrisis approaches that provide rapid access to transitional team-based care using critical time intervention strategies. It also highlights the development of state, county, and funder models for "care-traffic control" to ensure swift linkage to follow-up services, along with new funding models that support intensive community crisis stabilization during the postcrisis period. Emerging crisis systems can leverage these emerging services and approaches to facilitate successful transitions for individuals in need.

Vaginoplasty tips and tricks

ABSTRACT Vaginoplasty is a commonly performed surgery for the transfeminine patient. In this review, we discuss how to achieve satisfactory surgical outcomes, and highlight solutions to common complications involved with the surgery, including: wound separation, vaginal stenosis, hematoma, and rectovaginal fistula. Pre-operative evaluation and standard technique are outlined. Goal outcomes regarding aesthetics, creation of a neocavity, urethral management, labial appearance, vaginal packing and clitoral sizing are all described. Peritoneal vaginoplasty technique and visceral interposition technique are detailed as alternatives to the penile inversion technique in case they are needed to be used. Post-operative patient satisfaction, patient care plans, and solutions to common complications are reviewed.

Cerebral malaria [letter]

When young children are infected with P. falciparum; meningitis is often incidentally associated with parasitaemia and can be difficult to distinguish clinically from cerebral malaria. There is yet no clear evidence that lumbar puncture is dangerous in cerebral malaria and it is reasonable to do lumbar punctures to exclude bacterial meningitis in children with fever and coma in areas where malaria is endemic