Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation.

Genetic screens in simple model organisms have identified many of the key components of the conserved signal transduction pathways that are oncogenic when misregulated. Here, we identify H37N21.1 as a gene that regulates vulval induction in let-60(n1046gf), a strain with a gain-of-function mutation in the Caenorhabditis elegans Ras orthologue, and show that somatic deletion of Nrbp1, the mouse orthologue of this gene, results in an intestinal progenitor cell phenotype that leads to profound changes in the proliferation and differentiation of all intestinal cell lineages. We show that Nrbp1 interacts with key components of the ubiquitination machinery and that loss of Nrbp1 in the intestine results in the accumulation of Sall4, a key mediator of stem cell fate, and of Tsc22d2. We also reveal that somatic loss of Nrbp1 results in tumourigenesis, with haematological and intestinal tumours predominating, and that nuclear receptor binding protein 1 (NRBP1) is downregulated in a range of human tumours, where low expression correlates with a poor prognosis. Thus NRBP1 is a conserved regulator of cell fate, that plays an important role in tumour suppression

A multi-centre survey reveals variations in the standard treatments and treatment modifications for head and neck cancer patients during Covid-19 pandemic

BACKGROUND: The onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the Covid-19 pandemic in UK. METHODOLOGY: The UK National Cancer Research Institute (NCRI) Head and Neck Clinical Studies Group initiated a multi-centre survey using questionnaire to investigate the effect on feeding tube practice, radiotherapy (RT) fractionation and volumes, use of chemotherapy in the neo-adjuvant, adjuvant and palliative setting, the use of immunotherapy in the palliative setting, access to radiology and histopathology services, availability of surgical procedures. RESULTS: 30 centres were approached across UK; 23 (76.7%) centres responded and were included in the survey. There were differences in the standard practices in feeding tube policy, RT dose and fractionation as well as concurrent chemotherapy use. 21 (91%) participating centres had at least one treatment modification. 15 (65%) centres initiated a change in radical RT; changing to either a hypofractionation or acceleration schedule. For post-operative RT 10 centres (43.5%) changed to a hypofractionation schedule.12 (52.2%) centres stopped neo-adjuvant chemotherapy for all patients; 13 (56.5%) centres followed selective omission of chemotherapy in concurrent chemo-radiotherapy patients, 17 (73.9%) centres changed first-line chemotherapy treatment to pembrolizumab (following NHS England’s interim guidance) and 8 (34.8%) centres stopped the treatment early or offered delays for patients that have been already on systemic treatment. The majority of centres did not have significant changes associated with surgery, radiology, histopathology and dental screening. CONCLUSION: There are variations in the standard of practice and treatment modifications for head and neck cancer patients during Covid-19 pandemic. A timely initiative is required to form a consensus on head and neck cancer management in the UK and other countries

The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner

Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O6-mG DNA methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease

What Design Research Does ... : 62 Cards Highlighting the Power and Impact of UK-based Design Research in Addressing a Range of Complex Social, Economic, Cultural and Environmental Issues

Design research makes a significant contribution to the UK economy and society as a whole. Ever since the establishment of the Government Schools of Design in the nineteenth century, the UK has been widely acknowledged as an international leader in design research. Following this lead, the What Design Research Does… cards highlight the wide range of social, economic, cultural and environmental impacts that design research, funded and based in the UK, makes all over the world. The 62 cards illustrate unambiguously the positive changes that contemporary UK-based design researchers are making in many complex issues. Each What Design Research Does… card lists the challenges and issues faced by the design researchers, who they collaborated with, the research methods and approaches taken, the outcomes of the design research, what the main results and findings have been, and what impact the design research has had. In short, the What Design Research Does… cards clearly articulate the breadth of social, economic, cultural and environmental impacts that UK-based design researchers are achieving today

Pain Management Experiences Among Hospitalized Postcraniotomy Brain Tumor Patients

Background: Brain tumors account for the majority of central nervous system tumors, and most are removed by craniotomies. Many postcraniotomy patients experience moderate or severe pain after surgery, but patient perspectives on their experiences with pain management in the hospital have not been well described. Objective: The aim of this study was to describe how patients who have undergone a craniotomy for brain tumor removal experience pain management while hospitalized. Methods: Qualitative descriptive methods using semistructured interviews were conducted with patients on a neurological step-down unit in an urban teaching hospital in the Midwest United States. Interviews focused on how patients experienced postcraniotomy pain and how it was managed. Narratives were analyzed with standard content analytic procedures. Results: Twenty-seven participants (median age, 58.5 years; interquartile range, 26-41 years; range, 21-83 years) were interviewed. The majority were white (n = 25) and female (n = 15) and had an anterior craniotomy (n = 25) with sedation (n = 17). Their pain experiences varied on 2 dimensions: salience of pain during recovery and complexity of pain management. Based on these dimensions, 3 distinct types of pain management experiences were identified: (1) pain-as-nonsalient, routine pain management experience; (2) pain-as-salient, routine pain management experience; and (3) pain-as-salient, complex pain management experience. Conclusions: Many postcraniotomy patients experience their pain as tolerable and/or pain management as satisfying and effective; others experience pain and pain management as challenging. Implications for practice: Clinicians should be attuned to needs of patients with complex pain management experiences and should incorporate good patient/clinician communication

Pain Quality Among Hospitalized Postcraniotomy Brain Tumor Patients

Purpose/aims: The aim of this study was to describe how persons given a diagnosis of a brain tumor who have had a craniotomy describe the quality of their pain after surgery. Design: A qualitative descriptive design was used. Methods: Qualitative descriptive methods as described by Sandelowski guided this study. Semistructured interviews were conducted with patients hospitalized on a neurological step-down unit in an urban teaching hospital in the Midwestern United States. Interviews focused on the quality of participants' pain after surgery. Narratives were analyzed using standard content analysis. Results: Twenty-seven participants were interviewed. Most were White and female. Most underwent a craniotomy using an anterior approach with sedation. Participants described the quality of their pain with 6 different types of descriptors: pain as pressure, pain as tender or sore, pain as stabbing, pain as throbbing, pain as jarring, and pain as itching. Conclusions: Participants' descriptions of their pain quality after surgery provide a different understanding than do numerical pain ratings. Clinicians should use questions to explore patients' individual pain experiences, seeking to understand the quality of patients' pain and their perceptions