Complement is increased in treatment resistant rectal cancer and modulates radioresistance.

Resistance to neoadjuvant chemoradiation therapy (neo-CRT) is a significant clinical problem in the treatment of locally advanced rectal cancer. Identification of novel therapeutic targets and biomarkers predicting therapeutic response is required to improve patient outcomes. Increasing evidence supports a role for the complement system in resistance to anti-cancer therapy.

The genome sequences of the marine diatom strain UHM3201 (Schvarcz, Stancheva & Steward, 2022) and its nitrogen-fixing, endosymbiotic cyanobacterium.

We present the genome assembly of the pennate diatom strain UHM3201 (Ochrophyta; Bacillariophyceae; Rhopalodiales; Rhopalodiaceae) and that of its cyanobacterial endosymbiont (Chroococcales: Aphanothecaceae). The genome sequence of the diatom is 60.3 megabases in span, and the cyanobacterial genome has a length of 2.

Promoting Activity, Independence, and Stability in Early Dementia and mild cognitive impairment (PrAISED): randomised controlled trial.

Objective: To determine the effectiveness of an exercise and functional activity therapy intervention in adults with early dementia or mild cognitive impairment compared with usual care.

Design: Randomised controlled trial.

Setting: Participants' homes and communities at five sites in the United Kingdom.

The facilitators and barriers to improving functional activity and wellbeing in people with dementia: a qualitative study from the process evaluation of Promoting Activity, Independence and Stability in Early Dementia (PrAISED).

Background: The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with dementia. A Randomised Controlled Trial showed no measurable benefits in activities of daily living, physical activity or quality of life.

Objective: To explore participants' responses to PrAISED and explain why an intervention that might be expected to have produced measurable health gains did not do so.

Metformin is a metabolic modulator and radiosensitiser in rectal cancer.

Resistance to neoadjuvant chemoradiation therapy, is a major challenge in the management of rectal cancer. Increasing evidence supports a role for altered energy metabolism in the resistance of tumours to anti-cancer therapy, suggesting that targeting tumour metabolism may have potential as a novel therapeutic strategy to boost treatment response. In this study, the impact of metformin on the radiosensitivity of colorectal cancer cells, and the potential mechanisms of action of metformin-mediated radiosensitisation were investigated.

Conversation Analysis Based Simulation (CABS): A method for improving communication skills training for healthcare practitioners.

Background: Actors portraying simulated patients are widely used in communication skills training in healthcare, but debates persist over the authenticity of these interactions. However, healthcare professionals value simulation-based training because of the opportunity to think and react in real time, which alternatives cannot provide.

Objective: To describe a method for the use of simulation which maximises authenticity by grounding training in real, observed, patterns of patient communication.

Filial Cannibalism Leads to Chronic Nest Failure of Eastern Hellbender Salamanders ().

AbstractIn species that provide parental care, parents will sometimes cannibalize their own young (i.e., filial cannibalism).

Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel).

Thinking inside the box: intracellular roles for complement system proteins come into focus.

Over the last decade, perspectives on the complement system in the context of cancer have shifted, with complement proteins now implicated in many of the hallmarks of cancer. Systemically, the generation of complement anaphylatoxin C5a, the most potent inflammatory mediator of the cascade, occurs following convertase-mediated cleavage of complement component C5. In a recent manuscript, Ding et al.

Chronic pain in people living with dementia: challenges to recognising and managing pain, and personalising intervention by phenotype.

Pain is common in people with dementia, and pain can exacerbate the behavioural and psychological symptoms of dementia. Effective pain management is challenging, not least in people with dementia. Impairments of cognition, communication and abstract thought can make communicating pain unreliable or impossible.

A Distinctive γδ T Cell Repertoire in NOD Mice Weakens Immune Regulation and Favors Diabetic Disease.

Previous studies in mice and humans suggesting that T cells play a role in the development of type 1 diabetes have been inconsistent and contradictory. We attempted to resolve this for the type 1 diabetes-prone NOD mice by characterizing their T cell populations, and by investigating the functional contributions of particular T cells subsets, using V-gene targeted NOD mice. We found evidence that NOD V4+ T cells inhibit the development of diabetes, and that the process by which they do so involves IL-17 production and/or promotion of regulatory CD4+ αβ T cells (Tregs) in the pancreatic lymph nodes.

Impact of COVID-19 lockdown on physical exercise among participants receiving the Promoting Activity, Independence and Stability in Early Dementia (PrAISED) intervention: a repeated measure study.

Background: The potential decrease in daily physical activity associated with the COVID-19 pandemic lockdowns may have a negative impact on people living with dementia. Given the limited literature around the effects of home confinement in people living with dementia, this study investigated changes in physical exercise levels of participants in the intervention arm of the Promoting Activity, Independence and Stability in Early Dementia (PrAISED) Randomised Controlled Trial during the first COVID-19 national lockdown. It hypothesised that participants would maintain physical exercise levels.

Becoming aware of γδ T cells.

The discovery that B cells and αβ T cells exist was predictable: These cells gave themselves away through their products and biological effects. In contrast, there was no reason to anticipate the existence of γδ T cells. Even the accidental discovery of a novel TCR-like gene (later named γ) that did not encode TCR α or β proteins did not immediately change this.

PD-1 blockade enhances chemotherapy toxicity in oesophageal adenocarcinoma.

Chemotherapy upregulates immune checkpoint (IC) expression on the surface of tumour cells and IC-intrinsic signalling confers a survival advantage against chemotherapy in several cancer-types including oesophageal adenocarcinoma (OAC). However, the signalling pathways mediating chemotherapy-induced IC upregulation and the mechanisms employed by ICs to protect OAC cells against chemotherapy remain unknown. Longitudinal profiling revealed that FLOT-induced IC upregulation on OE33 OAC cells was sustained for up to 3 weeks post-treatment, returning to baseline upon complete tumour cell recovery.

Avoiding repair, maintaining face: Responding to hard-to-interpret talk from people living with dementia in the acute hospital.

People living with dementia (PLWD) are almost always admitted to the acute hospital for reasons unrelated to their dementia, finding themselves in the unfamiliar environment of a Health Care of Older Persons acute ward. The effect of this environment creates a challenge not just for a PLWD themselves, but also for the staff who care for them. Concerns have been raised by both policy makers and staff about the quality of communication between hospital staff and PLWD.

Divergent effects of exendin-4 and interleukin-6 on rat colonic secretory and contractile activity are associated with changes in regional vagal afferent signaling.

Background: The pro-inflammatory cytokine, interleukin (IL)-6 is elevated in individuals with the functional bowel disorder, irritable bowel syndrome (IBS). IL-6 can independently modify intestinal secreto-motor function, thereby contributing to IBS pathophysiology. Additionally, hormonal changes may underlie symptom flares.

Complement in Tumourigenesis and the Response to Cancer Therapy.

In recent years, our knowledge of the complement system beyond innate immunity has progressed significantly. A modern understanding is that the complement system has a multifaceted role in malignancy, impacting carcinogenesis, the acquisition of a metastatic phenotype and response to therapies. The ability of local immune cells to produce and respond to complement components has provided valuable insights into their regulation, and the subsequent remodeling of the tumour microenvironment.

Tele-Rehabilitation for People with Dementia during the COVID-19 Pandemic: A Case-Study from England.

Unlabelled: Introduction The Promoting Activity, Independence and Stability in Early Dementia (PrAISED) is delivering an exercise programme for people with dementia. The Lincolnshire partnership National Health Service (NHS) foundation Trust successfully delivered PrAISED through a video-calling platform during the Coronavirus Disease 2019 (COVID-19) pandemic.

Methods: This qualitative case-study aimed to identify participants that video delivery worked for, to highlight its benefits and its challenges.

Protocol for the process evaluation of the Promoting Activity, Independence and Stability in Early Dementia (PrAISED), following changes required by the COVID-19 pandemic.

Introduction: The Promoting Activity, Independence and Stability in Early Dementia (PrAISED) randomised controlled trial (RCT) is evaluating a home-based, face-to-face, individually tailored, activity and exercise programme for people living with dementia. Social distancing requirements following the COVID-19 pandemic necessitated rapid changes to intervention delivery.

Methods And Analysis: A mixed-methods process evaluation will investigate how the changes were implemented and the impact that these have on participants' experience.

When people living with dementia say 'no': Negotiating refusal in the acute hospital setting.

A quarter of UK acute hospital beds are occupied by people living with dementia (PLWD). Concerns have been raised by both policy makers and carers about the quality of communication between hospital staff and PLWD. PLWD may experience communication impairments such as word finding difficulties, limited ability to construct coherent narratives and difficulties understanding others.