Targeting T-cell integrins in autoimmune and inflammatory diseases.

The recruitment of T cells to tissues and their retention there are essential processes in the pathogenesis of many autoimmune and inflammatory diseases. The mechanisms regulating these processes have become better understood over the past three decades and are now recognized to involve temporally and spatially specific interactions between cell-adhesion molecules. These include integrins, which are heterodimeric molecules that mediate in-to-out and out-to-in signalling in T cells, other leukocytes, and most other cells of the body. Integrin signalling contributes to T-cell circulation through peripheral lymph nodes, immunological synapse stability and function, extravasation at the sites of inflammation, and T-cell retention at these sites. Greater understanding of the contribution of integrin signalling to the role of T cells in autoimmune and inflammatory diseases has focused much attention on the development of therapeutics that target T-cell integrins. This literature review describes the structure, activation, and function of integrins with respect to T cells, then discusses the use of integrin-targeting therapeutics in inflammatory bowel disease, multiple sclerosis, and psoriasis. Efficacy and safety data from clinical trials and post-marketing surveillance are presented for currently approved therapeutics, therapeutics that have been withdrawn from the market, and novel therapeutics currently in clinical trials. This literature review will inform the reader of the current means of targeting T-cell integrins in autoimmune and inflammatory diseases, as well as recent developments in the field.

Is Social Gender Transition Associated with Mental Health Status in Children and Adolescents with Gender Dysphoria?

Social gender transition is an increasingly accepted intervention for gender variant children and adolescents. To date, there is scant literature comparing the mental health of children and adolescents diagnosed with gender dysphoria who have socially transitioned versus those who are still living in their birth-assigned gender. We examined the mental health of children and adolescents referred to the Gender Identity Development Service (GIDS), a specialist clinic in London, UK, who had socially transitioned (i.e., were living in their affirmed gender and/or had changed their name) versus those who had not socially transitioned. Referrals to the GIDS were aged 4-17 years. We assessed mental health correlates of living in one's affirmed gender among 288 children and adolescents (208 birth-assigned female; 210 socially transitioned) and of name change in 357 children and adolescents (253 birth-assigned female; 214 name change). The presence or absence of mood and anxiety difficulties and past suicide attempts were clinician rated. Living in role and name change were more prevalent in birth-assigned females versus birth-assigned males. Overall, there were no significant effects of social transition or name change on mental health status. These findings identify the need for more research to understand how social transition influences mental health, including longitudinal studies that allow for more confident inferences to be made regarding the relationship between social transition and mental health in young people with gender dysphoria.

Shifts in demographics and mental health co-morbidities among gender dysphoric youth referred to a specialist gender dysphoria service.

Past research has identified shifts in the demographics and co-occurring mental health issues of youth referred to certain gender dysphoria services. The present study examined shifts in demographics (age, sex and social transition status), social adversity (bullying experiences and abuse) and psychological functioning (mood, anxiety, suicidality and autism spectrum disorder) at time of referral (of both children and adolescents) to the Gender Identity Development Service, London between the years of 2012 and 2015. Patients were 782 children and adolescents (M = 13.94, SD = 2.94, range 4-17; 63.8% assigned female at birth). Little change in sex ratio or age was observed between these two time points. However, we observed greater rates of depression and anxiety of birth-assigned females (but not birth-assigned males) in the more recent cohort, at the same time that reported social adversity (bullying and abuse) was falling. Also, of interest, the proportion of young people who had partially or fully socially transitioned prior to contact with the service had increased overtime. We discuss potential factors driving these shifts and their implications for supporting recent cohorts of gender diverse young people.

School refusal and isolation: The perspectives of five adolescent school refusers in London, UK.

Research has identified a subset of young people who feel unable to engage in mainstream education. Given the hard-to-reach nature of this group, their views on what has caused their isolation from others have received little focus in previous literature. The present study aimed to explore the experiences and views of a subset of young people seen within an inner London Pupil Referral Unit who were extremely socially withdrawn and unable to attend mainstream education. They were asked what they believe led them to their current situation, the impact of isolation, how their life is going and what they value. Key themes identified were the role of anxiety in withdrawal from education and the protective capacity of social contact, even via social media, in preventing negative outcomes of withdrawal. Sleep, health, education, family and social contact were identified as risk and protective factors and were also things participants identified as values. This research provides insight into potential ways to support young people in returning to mainstream education as well as ideas for preventative measures that may protect future generations from such extreme isolation. This research was conducted before the COVID-19 pandemic, but lessons learned bear relevance in current times.

A Mild Method for Making MIDA Boronates.

We disclose that a predried form of methyliminodiacetic acid (MIDA), MIDA anhydride, acts as both a source of the MIDA ligand and an in situ desiccant to enable a mild and simple MIDA boronate synthesis procedure. This method expands the range of sensitive boronic acids that can be converted into their MIDA boronate counterparts. Further utilizing unique properties of MIDA boronates, we have developed a MIDA Boronate Maker Kit which enables the direct preparation and purification of MIDA boronates from boronic acids using only heating and centrifuge equipment that is widely available in laboratories that do not specialize in organic synthesis.

Working with school-refusing young people in Tower Hamlets, London.

This study looks at the local context, describing quantitative data from a subset of young people seen within the inner London Tower Hamlets Pupil Referral Unit (PRU) that are extremely socially withdrawn and unable to attend mainstream education. The core aim of this research was to examine the views of professionals who work with and for these young people. Qualitative group interviews were used to gain a deeper understanding of the needs of these young people, what might contribute to their withdrawal from school and what needs to be done to help them reintegrate. Professionals reported that these young people were highly complex in terms of their needs and presentation and that there is a lack of clarity around what causes these young people to withdraw. They agreed that a more intensive multilayered intervention was required to meet their needs. Interventions that include gradual socialization, parental involvement and which address the role of technology were indicated. However, more research is needed to clarify how to effectively intervene.