Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation

Gift/economy: Drama and the politics of gift-giving in early modern England.

Gift/economy: Drama and the politics of gift-giving in early modern England

An investigation of the preparation of insoluble cellulose sulphates and their use for the isolation of lipoproteins from serum : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Chemistry at Massey University, New Zealand

The aim of this thesis was to prepare an insoluble sulphated polysaccharide and explore its potential as a rapid column chromatographic method for the isolation and separation of lipoproteins directly from serum. Regenerated cellulose crosslinked with formaldehyde was found to be relatively inert towards esterification. A degree of sulphation of 0.5 milliequivalents per gram could be obtained but the product had poor hydraulic properties. Epichlorohydrin crosslinked regenerated cellulose was found to be readily sulphated so long as the matrix was highly crosslinked (50-100% v/w). The reactivity of the matrix was retained at low levels of crosslinking if hydroxypropyl groups were introduced with propylene oxide. The hydroxypropylated regenerated celluloses were readily sulphated up to four milliequivalents per gram with minimal degradation of the cellulose chain. HP-cellulose 8-50 sulphates proved to be very successful in the selective isolation of the beta lipoproteins (VLDL plus LDL) directly from serum over a wide range of conditions. The conditions necessary for the preparation of pure alpha lipoprotein (HDL) were found to be more critical. Employing conditions so that all of the alpha lipoprotein (HDL) was sequested completely from serum resulted in it being contaminated by other serum proteins. Under other conditions where the alpha lipoprotein (HDL) was obtained without contamination by other serum proteins, it appeared that a small sub-fraction of the alpha lipoprotein remained in the serum

The Impact of Adherence to the Traditional Mediterranean Diet and Sex Differences on Global Cognitive Functioning: a Systematic Review and Meta-analysis

Contradictory findings in reviews that assess the relationship between the Mediterranean Diet (MedDiet) and cognitive functioning have been attributed to heterogeneity in the criteria used to assess MedDiet and cognition, and differences in the location or cultural habits of the populations studied. Few reviews have examined the relationship between dietary adherence and cognition or considered the impact of sex differences. This systematic review and meta-analysis examines the relationship between adherence to the MedDiet and cognitive functioning of healthy older adults (50+). We included isolated data from Mediterranean regions and considered differential outcomes based on sex. A search of PubMed, Cochrane Library, EMBASE, Scopus and Web of Science from 2011 to 2018 identified five longitudinal cohort studies (n = 3368) and one randomized controlled trial (RCT; n = 239 intervention; n = 95 controls). The primary outcome of interest was global cognitive functioning. Meta-analysis of cohort studies revealed a significant association between MedDiet adherence and cognitive functioning (n = 3368, r = 0.09, p = 0.012), an effect greater than previously reported. Meta-regression demonstrated that the effect size was stronger with improved quality of study reporting (p = 0.01). Sex did not impact cognitive outcomes, but sex differences in levels of adherence were reported in individual studies. There might be a stronger association between MedDiet and cognitive functioning for older adults from Mediterranean countries compared to other geographical locations, perhaps due to higher adherence and/or longer exposure over the life course. Results are compared to those of prior meta-analyses, and the impact of sources of heterogeneity is considered. The potential influence of sex and gender, as biological and social constructs, on dietary adherence is discussed

Discovery of Highly Potent, Selective, and Efficacious Small Molecule Inhibitors of ERK1/2

Using structure-based design, a novel series of pyridone ERK1/2 inhibitors was developed. Optimization led to the identification of (<i>S</i>)-<b>14k</b>, a potent, selective, and orally bioavailable agent that inhibited tumor growth in mouse xenograft models. On the basis of its in vivo efficacy and preliminary safety profiles, (<i>S</i>)-<b>14k</b> was selected for further preclinical evaluation