Is it Still Ok to be Ok? Mental Health Labels as a Campus Technology.

This article uses ethnography and coproduced ethnography to investigate mental health labels amongst university students in the UK. We find that although labels can still be a source of stigma, they are also both necessary and useful. Students use labels as 'campus technologies' to achieve various ends. This includes interaction with academics and administrators, but labels can do more than make student distress bureaucratically legible. Mental health labels extend across the whole student social world, as a pliable means of negotiating social interaction, as a tool of self-discovery, and through the 'soft-boy' online archetype, they can be a means of promoting sexual capital and of finessing romantic encounters. Labels emerge as flexible, fluid and contextual. We thus follow Eli Clare in attending to the varying degrees of sincerity, authenticity and pragmatism in dealing with labels. Our findings give pause to two sets of enquiry that are sometimes seen as opposed. Quantitative mental health research relies on what appear to be questionable assumptions about labels embedded in questionnaires. But concerns about the dialogical power of labels to medicalise students also appears undermined.

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase.

Sufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoenzymatic synthesis of sugar nucleotide tools to probe a critical enzyme within alginate biosynthesis, GDP-mannose dehydrogenase (GMD). We first synthesise C6-modified glycosyl 1-phosphates, incorporating 6-amino, 6-chloro and 6-sulfhydryl groups, followed by their evaluation as substrates for enzymatic pyrophosphorylative coupling. The development of this methodology enables access to GDP 6-chloro-6-deoxy-ᴅ-mannose and its evaluation against GMD.

Using analogue data to substantiate long-term durability of gene therapies: a narrative review.

The number of gene therapies in clinical trials and moving toward licensure is increasing. Most gene therapies are designed to achieve long-term effects, but at licensure the data to support claims of long-term durability are often limited, as long-term monitoring studies are often part of post-approval commitments by companies. Health technology assessors must therefore assess the potential for the long-term durability of a product and the potential cost-effectiveness based on the data available. The authors explored the benefit of strengthening the ability to infer durability of effect using analogue category data. Different analogue categories were assessed for the potential to substantiate claims of sustainability of effect for gene therapies by leveraging biological plausibility arguments. The authors propose a pathway for identifying potential analogues. Such a pathway should help establish plausible or theoretical long-term outcomes that can be considered in value assessments of gene therapies.

Many diseases, affecting all parts of the body, can be treated with gene therapy. Gene therapies make changes to a person's genes by either replacing or inactivating a gene that is causing disease or by adding new genes that can fight diseases such as cancers. These therapies have the potential to cure patients of the disease for their lifetime. When decisions are being made over whether gene therapies are safe and work well in patients, it can be difficult to understand if they will maintain their benefits to a person over a lifetime, as they have only been studied in clinical trials for a much shorter amount of time. In this paper, the authors explore whether information around the benefits of therapies that work in a similar way, or target similar diseases, can be used to strengthen an understanding of how well newer therapies work over a long period of time. The authors propose a pathway that can be followed to identify the suitability of a comparison between different therapies and how the evidence of benefit over time can be interpreted. This information will be useful for developers of gene therapies who are trying to generate evidence of long-term benefit to patients, as well as for decision makers who need to understand how well these gene therapies will work over a patient's lifetime.

Inhibition of the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa Using Targeted Sugar Nucleotide Probes.

Sufferers of cystic fibrosis are at extremely high risk for contracting chronic lung infections. Over their lifetime, one bacterial strain in particular, Pseudomonas aeruginosa, becomes the dominant pathogen. Bacterial strains incur loss-of-function mutations in the mucA gene that lead to a mucoid conversion, resulting in copious secretion of the exopolysaccharide alginate. Strategies that stop the production of alginate in mucoid Pseudomonas aeruginosa infections are therefore of paramount importance. To aid in this, a series of sugar nucleotide tools to probe an enzyme critical to alginate biosynthesis, guanosine diphosphate mannose dehydrogenase (GMD), have been developed. GMD catalyzes the irreversible formation of the alginate building block, guanosine diphosphate mannuronic acid. Using a chemoenzymatic strategy, we accessed a series of modified sugar nucleotides, identifying a C6-amide derivative of guanosine diphosphate mannose as a micromolar inhibitor of GMD. This discovery provides a framework for wider inhibition strategies against GMD to be developed.