Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study.

Background And Objectives: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry.

The experience of navigating sexuality for transgender and gender non-conforming people: a meta-ethnographic review.

Background: The current research builds on a previous review of the literature which explored sexuality during gender transition. There has been increased attention toward TGNC people across academic, political, and healthcare fields since the previous review, as well as shifts in language use and health interventions, justifying a need for more contemporary understandings.

Aim: The current systematic review explores the experience of sexuality during gender transition.

Key Points to Consider When Studying RNA Remodeling by Proteins.

Cellular RNAs depend on proteins for efficient folding to specific functional structures and for transitions between functional structures. This dependence arises from intrinsic properties of RNA structure. Specifically, RNAs possess stable local structure, largely in the form of helices, and there are abundant opportunities for RNAs to form alternative helices and tertiary contacts and therefore to populate alternative structures.

Key points to consider when studying RNA remodeling by proteins.

Cellular RNAs depend on proteins for efficient folding to specific functional structures and for transitions between functional structures. This dependence arises from intrinsic properties of RNA structure. Specifically, RNAs possess stable local structure, largely in the form of helices, and they have abundant opportunities to form alternative helices and tertiary contacts and therefore to populate alternative structures.

Ground-state coordination of a catalytic metal to the scissile phosphate of a tertiary-stabilized Hammerhead ribozyme.

Although the Hammerhead ribozyme (HHRz) has long been used as a model system in the field of ribozyme enzymology, several details of its mechanism are still not well understood. In particular, significant questions remain concerning the disposition and role of catalytic metals in the HHRz. Previous metal-rescue experiments using a "minimal" HHRz resulted in prediction of a catalytic metal that is bound in the A9/G10.

The identity of the nucleophile substitution may influence metal interactions with the cleavage site of the minimal hammerhead ribozyme.

Potential metal interactions with the cleavage site of a minimal hammerhead ribozyme (mHHRz) were probed using (31)P NMR-detected Cd(2+) titration studies of HHRz constructs containing a phosphorothioate (PS) modification at the cleavage site. The mHHRz nucleophile position was replaced by either a 2'-F or a 2'-NH(2) in order to block cleavage activity during the study. The 2'-F/PS cleavage site mHHRz construct, in which the 2'-F should closely imitate the atom size and electronegativity of a 2'-OH, demonstrates low levels of metal ion association (<1 ppm (31)P chemical shift changes).