The intrinsic apoptotic pathway lies upstream of reactive species production in cortical neurons and age-related oxidative stress in the brain.

A BAX- and mitochondria-dependent production of reactive oxygen species (ROS) and reactive species (reactive nitrogen species, RNS) lying downstream of these ROS occurs in apoptotic and nonapoptotic mouse sympathetic neurons and cerebellar granule cells in cell culture. These ROS have been shown to lie downstream of caspase 3 in mouse sympathetic neurons. Here we show that BAX is necessary for similar ROS production in apoptotic and nonapoptotic mouse cortical neurons in cell culture and that it also positively regulates oxidative stress in the brains of mice of different ages.

Outcomes of National Survey of the Practice of Hepatocellular Carcinoma Surveillance.

Background & Aim: HCC has significantly improved outcomes when detected early. Guidelines recommend biannual surveillance with ultrasound (US) and/or AFP in at-risk individuals. This survey aimed to describe HCC surveillance adherence/practices amongst the NHS hospitals in the UK.

A Hippocratic Oath for Mathematicians? Mapping the Landscape of Ethics in Mathematics.

While the consequences of mathematically-based software, algorithms and strategies have become ever wider and better appreciated, ethical reflection on mathematics has remained primitive. We review the somewhat disconnected suggestions of commentators in recent decades with a view to piecing together a coherent approach to ethics in mathematics. Calls for a Hippocratic Oath for mathematicians are examined and it is concluded that while lessons can be learned from the medical profession, the relation of mathematicians to those affected by their work is significantly different.

Polyps seen but not removed during index colonoscopy: an underestimated inefficiency in endoscopy practice.

Background And Aims: In the United Kingdom endoscopists are certified for independent practice once competent in the removal of polyps up to 20 mm in size. Where polyps are detected but not removed during the index colonoscopy, a repeat procedure is required. The aim of this study was to identify the proportion of polyps <20 mm that were not removed at the time of diagnosis.

Comprehensive Imaging Characterization of Colorectal Liver Metastases.

Colorectal liver metastases (CRLM) have heterogenous histopathological and immunohistochemical phenotypes, which are associated with variable responses to treatment and outcomes. However, this information is usually only available after resection, and therefore of limited value in treatment planning. Improved techniques for disease assessment, which can characterise the variable tumour biology, would support further personalization of management strategies.

Long-term nitrogen addition does not sustain host tree stem radial growth but doubles the abundance of high-biomass ectomycorrhizal fungi.

Global change has altered nitrogen availability in boreal forest soils. As ectomycorrhizal fungi play critical ecological functions, shifts in their abundance and community composition must be considered in the response of forests to changes in nitrogen availability. Furthermore, ectomycorrhizas are symbiotic, so the response of ectomycorrhizal fungi to nitrogen cannot be understood in isolation of their plant partners.

Assessing the dual-mycorrhizal status of a widespread tree species as a model for studies on stand biogeochemistry.

Viewing plant species by their mycorrhizal type has explained a range of ecosystem processes. However, mycorrhizal type is confounded with plant phylogeny and the environments in which mycorrhizal partners occur. To circumvent these confounding effects, "dual-mycorrhizal" plant species may be potential models for testing the influence of mycorrhizal type on stand biogeochemistry.

Impact of the COVID-19 pandemic on radiography practice: findings from a UK radiography workforce survey.

Objectives: Radiographers are key patient-facing healthcare professionals involved in many aspects of patient care. The working patterns and professional practice of the radiography workforce (RW) has been altered during the COVID-19 pandemic. This survey aimed to assess the impact of the pandemic on radiography practice in the United Kingdom (UK).

Population-level variation in host plant response to multiple microbial mutualists.

Premise: Multipartite mutualisms are widespread in nature, but population-level variation in these interactions is rarely quantified. In the model multipartite mutualism between legumes, arbuscular mycorrhizal (AM) fungi and rhizobia bacteria, host responses to microbial partners are expected to be synergistic because the nutrients provided by each microbe colimit plant growth, but tests of this prediction have not been done in multiple host populations.

Methods: To test whether plant response to associations with AM fungi and rhizobia varies among host populations and whether synergistic responses to microbial mutualists are common, we grew 34 Medicago truncatula populations in a factorial experiment that manipulated the presence or absence of each mutualist.

Baseline use of angiotensin-converting enzyme inhibitor/AT1 blocker and outcomes in hospitalized coronavirus disease 2019 African-American patients.

Objectives: The primary objective of this study is to determine the effect of baseline use of angiotensin-converting enzyme inhibitor (ACE-i)/AT1 blocker (ARB) on mortality in hospitalized coronavirus disease 2019 (Covid-19) African-American patients. The secondary objectives are, to determine the effect of baseline use of ACE-i/ARB on the need for mechanical ventilation, new dialysis, ICU care, and on composite of above-mentioned outcomes in the same cohort.

Methods: In this retrospective study, we analyzed data using electronic medical records from all hospitalized Covid-19 African-American patients, who either died in the hospital or survived to discharge between 2 March and 22 May 2020.

The intrinsic apoptotic pathway lies upstream of oxidative stress in multiple organs.

Oxidative stress increases with age in multiple organ systems and is implicated in the development of age-related pathologies in them. Studies from our laboratory show that the intrinsic pathway proapoptotic proteins BAX and caspase-3 (CASP3) lie upstream of mitochondrial production of oxidative stress-inducing reactive species (RS) such as reactive oxygen and reactive nitrogen species (ROS and RNS) in apoptotic and nonapoptotic neurons in cell culture. Our objective in this study was to determine if these findings could be generalized to the development of oxidative stress in nonneuronal tissues in vivo.

Demographics, comorbidities and outcomes in hospitalized Covid-19 patients in rural southwest Georgia.

Background: There is limited data on outcomes in patients with coronavirus disease 2019 (Covid-19) in rural United States (US). This study aimed to describe the demographics, and outcomes of hospitalized Covid-19 patients in rural Southwest Georgia.

Methods: Using electronic medical records, we analyzed data from all hospitalized Covid-19 patients who either died or survived to discharge between 2 March 2020 and 6 May 2020.

Recent advances in understanding and preventing oesophageal cancer.

Oesophageal cancer is a common cancer that continues to have a poor survival. This is largely in part due to its late diagnosis and early metastatic spread. Currently, screening is limited to patients with multiple risk factors via a relatively invasive technique.

Tumour subregion analysis of colorectal liver metastases using semi-automated clustering based on DCE-MRI: Comparison with histological subregions and impact on pharmacokinetic parameter analysis.

Purpose: To use a novel segmentation methodology based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to define tumour subregions of liver metastases from colorectal cancer (CRC), to compare these with histology, and to use these to compare extracted pharmacokinetic (PK) parameters between tumour subregions.

Materials And Methods: This ethically-approved prospective study recruited patients with CRC and ≥1 hepatic metastases scheduled for hepatic resection. Patients underwent DCE-MRI pre-metastasectomy.

The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice.

Oxidative stress, likely stemming from dysfunctional mitochondria, occurs before major cognitive deficits and neuropathologies become apparent in Alzheimer's disease (AD) patients and in mouse models of the disease. We previously reported that treating 2- to 7-month-old 3xTg-AD mice with the mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-Dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl](triphenyl)phosphonium methanesulfonate), a period when AD-like pathologies first manifest in them, prevents AD-like symptoms from developing. To elucidate further a role for mitochondria-derived oxidative stress in AD progression, we examined the ability of MitoQ to inhibit AD-like pathologies in these mice at an age in which cognitive and neuropathological symptoms have fully developed.

An Argument Against Drug Testing Welfare Recipients.

Programs of drug testing welfare recipients are increasingly common in US states and have been considered elsewhere. Though often intensely debated, such programs are complicated to evaluate because their aims are ambiguous-aims like saving money may be in tension with aims like referring people to treatment. We assess such programs using a proportionality approach, which requires that for ethical acceptability a practice must be reasonably likely to meet its aims, sufficiently important in purpose as to outweigh harms incurred, and lower in costs than feasible alternatives.

GIFTed Demons: deformable image registration with local structure-preserving regularization using supervoxels for liver applications.

Deformable image registration, a key component of motion correction in medical imaging, needs to be efficient and provides plausible spatial transformations that reliably approximate biological aspects of complex human organ motion. Standard approaches, such as Demons registration, mostly use Gaussian regularization for organ motion, which, though computationally efficient, rule out their application to intrinsically more complex organ motions, such as sliding interfaces. We propose regularization of motion based on supervoxels, which provides an integrated discontinuity preserving prior for motions, such as sliding.

Dissociation of JNK Activation from Elevated Levels of Reactive Oxygen Species, Cytochrome c Release, and Cell Death in NGF-Deprived Sympathetic Neurons.

Withdrawal of nerve growth factor (NGF) from sympathetic neurons causes their apoptotic death. Activation of c-Jun NH2-terminal kinase (JNK) may contribute to this death by the induction and phosphorylation of pro-apoptotic Bcl-2 proteins, such as Bax, that are involved in cytochrome c release from mitochondria and reactive oxygen species (ROS) production. Induction of either JNK or ROS may stimulate the other, and both may regulate release of apoptogenic factors from the mitochondria.

Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemotherapy: The Implications of Metabolic Nodal Response for Personalized Therapy.

Unlabelled: Only a minority of esophageal cancers demonstrates a pathologic tumor response (pTR) to neoadjuvant chemotherapy (NAC). F-FDG PET/CT is often used for restaging after NAC and to assess response. Increasingly, it is used during therapy to identify unresponsive tumors and predict pTR, using avidity of the primary tumor alone.

Imaging oligometastatic cancer before local treatment.

With the advent of novel treatment strategies to help widen the therapeutic window for patients with oligometastatic cancer, improved biomarkers are needed to reliably define patients who can benefit from these treatments. Multimodal imaging is one such option and should be optimised to comprehensively assess metastatic sites, disease burden, and response to neoadjuvant treatment in each disease setting. These features will probably remain important prognostic biomarkers, and are crucial in planning multidisciplinary treatment.

Pieces-of-parts for supervoxel segmentation with global context: Application to DCE-MRI tumour delineation.

Rectal tumour segmentation in dynamic contrast-enhanced MRI (DCE-MRI) is a challenging task, and an automated and consistent method would be highly desirable to improve the modelling and prediction of patient outcomes from tissue contrast enhancement characteristics - particularly in routine clinical practice. A framework is developed to automate DCE-MRI tumour segmentation, by introducing: perfusion-supervoxels to over-segment and classify DCE-MRI volumes using the dynamic contrast enhancement characteristics; and the pieces-of-parts graphical model, which adds global (anatomic) constraints that further refine the supervoxel components that comprise the tumour. The framework was evaluated on 23 DCE-MRI scans of patients with rectal adenocarcinomas, and achieved a voxelwise area-under the receiver operating characteristic curve (AUC) of 0.

Restaging oesophageal cancer after neoadjuvant therapy with (18)F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery.

Objectives: It is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk.

Methods: This was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by (18)F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014).