Interaction between perfluoro-octanoic sulfonate and common antibiotics induces developmental anomalies and lethality in Xenopus laevis.

Background: Perfluoroalkyl substances (PFAS) are persistent environmental contaminants previously used for industrial purposes as a non-stick coating and flame retardant. The stability of these molecules prevents their breakdown, which results in ground water contamination across the globe. Perfluoroalkyl substances molecules are known to bioaccumulate in various organisms.

Engineering an fgfr4 knockout zebrafish to study its role in development and disease.

Fibroblast growth factor receptor 4 (FGFR4) has a role in many biological processes, including lipid metabolism, tissue repair, and vertebrate development. In recent years, FGFR4 overexpression and activating mutations have been associated with numerous adult and pediatric cancers. As such, FGFR4 presents an opportunity for therapeutic targeting which is being pursued in clinical trials.

Reproductive hormones in relation to white matter hyperintensity volumes among midlife women.

Introduction: Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle-stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women.

Status epilepticus in POLG disease: a large multinational study.

We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed.

Engineering an knockout zebrafish to study its role in development and disease.

Fibroblast growth factor receptor 4 (FGFR4) has a role in many biological processes, including lipid metabolism, tissue repair, and vertebrate development. In recent years, FGFR4 overexpression and activating mutations have been associated with numerous adult and pediatric cancers. As such, presents an opportunity for therapeutic targeting which is being pursued in clinical trials.

Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants.

A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17-85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

Background And Purpose: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting.

Methods: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE.

Engineering Escherichia coli to produce aromatic chemicals from ethylene glycol.

Microbial overproduction of aromatic chemicals has gained considerable industrial interest and various metabolic engineering approaches have been employed in recent years to address the associated challenges. So far, most studies have used sugars (mostly glucose) or glycerol as the primary carbon source. In this study, we used ethylene glycol (EG) as the main carbon substrate.

Increased alcohol dehydrogenase 1 activity promotes longevity.

Several molecules can extend healthspan and lifespan across organisms. However, most are upstream signaling hubs or transcription factors orchestrating complex anti-aging programs. Therefore, these molecules point to but do not reveal the fundamental mechanisms driving longevity.

VGLL2-NCOA2 leverages developmental programs for pediatric sarcomagenesis.

Clinical sequencing efforts are rapidly identifying sarcoma gene fusions that lack functional validation. An example is the fusion of transcriptional coactivators, VGLL2-NCOA2, found in infantile rhabdomyosarcoma. To delineate VGLL2-NCOA2 tumorigenic mechanisms and identify therapeutic vulnerabilities, we implement a cross-species comparative oncology approach with zebrafish, mouse allograft, and patient samples.

A feasibility study to explore the use of digital treatment of sleep as a first-step intervention to improve adolescent mental health.

Introduction: Cognitive behavior therapy for insomnia (CBTi), delivered face-to-face or digitally, can improve the mental health of adults. Although insomnia is common in adolescents, the effects of digital CBTi on adolescent mental health have seldom been investigated.

Objectives: The aims of this study were to explore: (i) the acceptability of a digital CBTi intervention, Sleepio, as a first-step intervention for adolescents referred to specialist mental health services (CAMHS), (ii) the impact on sleep and mental health and (iii) subsequent CAMHS interventions.

A Thematic Analysis of Students' Perceptions and Experiences of Bullying in UK Higher Education.

Bullying in higher education (HE) has been relatively under-researched; despite its likely prevalence and impact on student wellbeing there is scant understanding of students' lived experiences of bullying. We conducted online and physical focus groups with UK HE students (40 undergraduates from 17 UK universities, mean age: 22), exploring their perceptions and experiences of bullying at university. Thematic analysis was used to identify key issues, specifically 1) the importance of a power imbalance and perpetuation of existing systemic inequality in a HE context; 2) bullying in HE is motivated by attainment of social and personal gains; 3) the tactics used to bully in HE resemble those seen in other contexts, but may be more nuanced; 4) bullying can be minimised and justified within HE, leading to its continued prevalence.

Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta-analysis.

Background: Adverse childhood experiences (ACEs) are associated with increased health risks across the life course. We aimed to estimate the annual health and financial burden of ACEs for 28 European countries.

Methods: In this systematic review and meta-analysis, we searched MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and Education Resources Information Center for quantitative studies (published Jan 1, 1990, to Sept 8, 2020) that reported prevalence of ACEs and risks of health outcomes associated with ACEs.

Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions.

Plasticity in multicellular organisms involves signaling pathways converting contexts-either natural environmental challenges or laboratory perturbations-into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts.

Markers of susceptibility to cardiac arrhythmia in experimental spinal cord injury and the impact of sympathetic stimulation and exercise training.

Injury to descending autonomic (sympathetic) pathways is common after high-level spinal cord injury (SCI) and associated with abnormal blood pressure and heart rate regulation. In individuals with high-level SCI, abnormal sympathovagal balance (such as during autonomic dysreflexia; paroxysmal hypertension provoked by sensory stimuli below the injury) is proarrhythmogenic. Exercise training is a key component of SCI rehabilitation and management of cardiovascular disease risk, but it is unclear whether exercise training influences susceptibility to cardiac arrhythmia.

Assessing recovery in treatment as usual provided by community child and adolescent mental health services.

Background: Despite the importance of routinely assessing the outcomes of everyday practice, few studies have reported outcome metrics for child and adolescent mental health services (CAMHS).

Aims: Our aim is to investigate reliable change and recovery rates for treatment as usual, provided by one community CAMHS over two time periods.

Method: We prospectively audited accepted consecutive referrals from November 2017 to January 2018, and April to September 2019.

Making sense of child and adolescent mental health services (CAMHS): An audit of the referral journey and the use of routine outcome measures (ROMS).

Background: There is increased emphasis on the national reporting of Routine Outcome Measures (ROMS) as a way of improving Child and Adolescent Mental Health Services (CAMHS). This data needs to be viewed in context so that reasons for outcome completion rates are understood and monitored over time.

Method: We undertook an in-depth prospective audit of consecutive referrals accepted into the Bath and North East Somerset, Swindon and Wiltshire (BSW) CAMHS service from November 2017 to January 2018 ( = 1074) and April to September 2019 ( = 1172).

Opportunities and Challenges for Microbial Synthesis of Fatty Acid-Derived Chemicals (FACs).

Global warming and uneven distribution of fossil fuels worldwide concerns have spurred the development of alternative, renewable, sustainable, and environmentally friendly resources. From an engineering perspective, biosynthesis of fatty acid-derived chemicals (FACs) is an attractive and promising solution to produce chemicals from abundant renewable feedstocks and carbon dioxide in microbial chassis. However, several factors limit the viability of this process.

Engineering Escherichia coli for the utilization of ethylene glycol.

Background: A considerable challenge in the development of bioprocesses for producing chemicals and fuels has been the high cost of feedstocks relative to oil prices, making it difficult for these processes to compete with their conventional petrochemical counterparts. Hence, in the absence of high oil prices in the near future, there has been a shift in the industry to produce higher value compounds such as fragrances for cosmetics. Yet, there is still a need to address climate change and develop biotechnological approaches for producing large market, lower value chemicals and fuels.

A Neuroimaging Preparation Protocol Tailored for Autism.

This paper describes the key basic elements required for a successful multi-parametric MRI data acquisition in awake children with autism. The procedure was designed by taking into account methodological challenges arising from the acquisition of Resting State fMRI (RS fMRI) data, and factors such as cost, time, and staff availability. The ultimate aim was to prepare an imaging preparation protocol with high transferability to the whole autism spectrum, adaptable for use in a multi-site research with multiple time points.

Hyperpolarized C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.

Purpose: To compare hyperpolarized carbon 13 (C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer.

Materials And Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent C MRI after injection of hyperpolarized [1-carbon 13 {C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The C-labeled lactate-to-pyruvate ratio derived from hyperpolarized C MRI and the pharmacokinetic parameters transfer constant ( ) and washout parameter ( ) derived from DCE MRI were compared before and after treatment.

Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized C label exchange between injected [1-C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic C MRSI was performed following injection of hyperpolarized [1-C]pyruvate.

Unraveling the cell-type dependent radiosensitizing effects of gold through the development of a multifunctional gold nanoparticle.

The radiosensitizing efficacy of gold is well established, however, there remain several significant barriers to the successful clinical translation of nano-sized gold particles (AuNPs). These barriers include: retaining stability in relevant biological sera, demonstrating effectiveness at clinically relevant AuNP concentrations and identifying the biological context where significant benefit is most likely to be achieved. Herein we have developed a AuNP preparation, stress-tested to provide effective protection from salt and serum mediated agglomeration.

Peptide functionalized gold nanoparticles: the influence of pH on binding efficiency.

We report herein on the synthesis of mixed monolayer gold nanoparticles (AuNPs) capped with both polyethylene glycol (PEG) and one of three peptides. Either a receptor-mediated endocytosis peptide, an endosomal escape pathway (H5WYG) peptide or the Nrp-1 targeting RGD peptide (CRGDK) labeled with FITC. All three peptides have a thiol containing cysteine residue which can be used to bind the peptides to the AuNPs.