Protein tyrosine phosphatases in glioma biology

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

The Health & Wellbeing of Children in the Early Years

Giving children the best start in life is by far the most effective way to address health inequalities in the long term. The wisest investment we can make to achieve the goal of a healthier population is during the first 1001 critical days of a child’s life. Good nutrition and safe environments supported by nurturing early relationships are the essential components of children’s cognitive, emotional and physical development. The importance of this age-range is acknowledged by the World Health Organisation’s Global Strategy for Women’s, Children’s and Adolescents’ Health, the UNICEF Baby Friendly Initiative and in England, both the NHS Long Term Plan and Public Health England’s 2016 guidance on ‘Giving every child the best start in life’. Covid-19 is having a continuing impact on babies born before and during the pandemic and children in the early years. The impact has been unequal for children, with a disproportionate number of BAME families, those living with poverty and children with SEND facing the greatest challenges. Parents and carers had less face-to-face interaction with health professionals and early years settings and studies reported families found it harder to stay active and access healthy food choices. In the UK, 14% of families with children experienced food insecurity during the first six months of the pandemic as opposed to 11.5% beforehand. There are now widespread and burgeoning concerns that Covid-19 has exacerbated nutritional problems linked to food insecurity including obesity, under-nourishment, nutrient deficiencies and mental health problems such as anxiety, low self-worth, and depression. Children have been subjected to violence and abuse at home as a corollary of lockdown whether as direct recipients or helpless observers. We are now reeling in the aftermath of such challenges as children’s emotional well-being and education faltered, instead of thriving. Children need to be put at the heart of any recovery plans to ensure Covid-19 is not the legacy of their future outcomes. It is probable that the true impact of the pandemic may not become clear for many years. Schools are already reporting an increasing number of their pupils requiring extra support with language and communication and personal social and emotional development. Early years settings were the one constant in the lives of young children providing a stable and safe space during Covid-19. They continue to play a central role in supporting parents, carers and young children in establishing lifelong healthy eating habits. Good quality early education has a positive impact on young children’s development and safe, excellent childcare enables parents and carers to work, while their children have the opportunity to interact with other children and be enriched by new challenges and experiences within a safe space. Nursery settings support children’s care and development from birth to five years and are a vital source of information, guidance and support for parents, carers and families. Early years providers continued to provide this support throughout the pandemic yet Covid-19 has impacted greatly on early years providers