I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection.

Dendritic cells (DC) are required for priming antigen-specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, inappropriate priming of auto-reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen-specific T cells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases.

The experiences of socially vulnerable groups in England during the COVID-19 pandemic: A rapid health needs assessment.

OBJECTIVES: This rapid health needs assessment was undertaken to urgently identify the needs of socially vulnerable groups arising during the first wave of cases of the COVID-19 pandemic in England. The objective was to develop recommendations for policy makers and stakeholders to mitigate adverse impacts on socially vulnerable groups throughout the COVID-19 response and recovery period. STUDY DESIGN: Rapid health needs assessment. METHODS: The needs assessment employed qualitative methods to systematically collect data about the knowledge and views of key informants through semi-structured interviews and focus groups. Participants were either topic experts providing services to socially vulnerable groups who routinely face barriers to healthcare access or experts by experience. Participants included people experiencing homelessness, sex workers, people from Gypsy, Roma and Traveller communities and people facing challenges due to their immigration status. Data was collected over a week period in April/May 2020 and followed by thematic analysis to examine interview transcripts. RESULTS: Forty-two participants were included in the study, half of whom were experts by experience. Challenges with accessing and following COVID-19 information and government guidance were described as affecting all groups, due to exclusion from digital technology, translated resources, tailored support and adequate housing. Altered delivery of healthcare services, such as the closure of outreach and drop-in services, remote consultations, and online patient registration, were noted by interviewees as worsening existing barriers to accessing healthcare. Being charged for NHS care remained a key fear for migrants. All groups' access to income, education and social support were reported as being impacted by service closures and job losses, putting them at higher risk of destitution. Isolation, loneliness and deteriorating mental health were frequently reported. CONCLUSIONS: This assessment has highlighted the disproportionate impact of the COVID-19 pandemic on socially vulnerable groups and demonstrated a plethora of unmet needs. As the effects of COVID-19 continue, it is imperative that the needs of these groups are urgently and explicitly addressed and prioritised. This is essential to promote engagement with test and trace services, enable isolation adherence, and achieve high vaccine uptake in socially vulnerable populations.

Assessing the Risk of Inpatient Violence in Autism Spectrum Disorder.

The Historical Clinical and Risk Management scale (HCR-20) is a structured clinical judgment tool used to assess risk of violence in secure settings. But the scale does not account for difficulties typical of patients with autism spectrum disorder, which are thought to contribute to their engagement in violent behaviors. The present study is a preliminary investigation of the association between risk assessment and physical and verbal violence in patients with autism spectrum disorder in a secure psychiatric hospital. Scores from the third version of HCR-20 (HCR-20V3) and violent episodes at three and six months following the initial assessment were extracted from an electronic record. The results support the use of the HCR-20V3 to assess the risk of overall and physical violence but not verbal aggression. Future studies are needed to identify which factors are associated with violent behaviors in patients with autism spectrum disorder.

A Focused Systematic Review of Pharmacological Treatment for Borderline Personality Disorder.

BACKGROUND: Medicines are routinely prescribed to treat borderline personality disorder (BPD) despite a relative lack of high-quality evidence and in breach of some treatment guidelines. An earlier Cochrane review of pharmacotherapy in BPD underlined the lack of evidence, encouraged the replication of earlier studies, but also emphasised the pressing need for more randomised placebo-controlled trials, and for those studies to employ broadened inclusion criteria. METHOD: The authors searched bibliographic databases, reference lists of articles and trials registers. Records were screened to identify those that met the inclusion criteria. Full-text articles were screened and assessed for eligibility. On-going trials of pharmacotherapy in BPD were also identified. RESULTS: Fifteen new studies of pharmacotherapy for BPD were identified since the earlier review. Eight of those examined second generation antipsychotics, two investigated mood stabilisers, three investigated antidepressants and two studied the effectiveness of opioid antagonists. Results for the effectiveness of antipsychotics appeared to be mixed. There has been little recent evidence to support the use of mood stabilisers. There is a lack of new placebo-controlled, randomised controlled trials investigating antidepressants and limited new evidence to support the use of opioid antagonists. CONCLUSIONS: The review revealed that there remains a dearth of high-quality research evidence to help patients, carers and clinicians make sound and safe evidence-based decisions about medicines to treat BPD.