Organometallic mediated radical polymerization

Controlled radical polymerization has become increasingly important over the past decade and a half, allowing for the facile synthesis of specific macromolecular architectures with excellent control over the chemical and physical properties. This article presents an organized and detailed review of one particular CRP technique, organometallic mediated radical polymerization (OMRP), focusing on the individual catalysts developed, their efficacy and monomer scope. Rhodium, cobalt, molybdenum, osmium, iron, palladium, titanium, chromium and vanadium mediated radical polymerizations are presented alongside organo-main group mediated reactions. A separate section reviews the types of copolymers which have been synthesized using OMRP techniques. An attempt is made to unify the many disparate names which have previously been used for OMRP by virtue of the common mechanistic aspects displayed by the different catalyst systems. A mechanistic discussion highlights the similarities and differences between these systems and examines the interplay between reversible termination and degenerative transfer OMRP and competing 1-electron redox processes

The association between later eating rhythm and adiposity in children and adolescents:a systematic review and meta-analysis

CONTEXT: Childhood adiposity, an important predictor of adult chronic disease, has been rising dramatically. Later eating rhythm, termed night eating, is increasing in adults but rarely studied in younger ages. OBJECTIVE: The objective of this study was to review the association between later eating rhythm and adiposity in children and adolescents. The aspects of later eating being considered included: energy intake (for evening main meal, evening snack, whole evening period, and around bedtime); timing (any food eaten at later timing); and meal frequency in the evening/night (evening main meal skipping, evening snack consumption). DATA SOURCES: Five databases (the Cochrane Library, CINAHL, Embase, MEDLINE (via OVID), and Web of Science) were searched for eligible articles published prior to and including August 2020. DATA EXTRACTION: Data extraction and quality assessment were conducted by 2 reviewers independently. DATA ANALYSIS: Forty-seven studies were included, all of which were observational. Meta-analysis showed positive associations between both higher energy intake around bedtime (odds ratio [OR] 1.19, 95% CI 1.06, 1.33) and evening main meal skipping (OR 1.30, 95% CI 1.14, 1.48), and adiposity. There was evidence to suggest that consuming evening snacks reduced adiposity, but it was very weak (OR 0.80, 95% CI 0.62, 1.05). No association was seen between eating later and adiposity (OR 1.04, 95% CI 0.68, 1.61). In the narrative analysis, approximately half of the studies suggested that there was no association between later eating rhythm and adiposity, either as a whole or within exposure subsets. CONCLUSION: The magnitude of the relationship between later eating rhythm and adiposity is very small, and may vary depending on which aspects of later eating rhythm are under consideration; however, the evidence for this conclusion is of very low certainty . Further research with a more consistent definition of “later timing”, and longitudinal studies in different populations, may lead to different conclusions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019134187

Accelerometer-measured sedentary time and cardiometabolic biomarkers:A systematic review

AbstractObjectiveWe conducted a systematic review to investigate the cross-sectional and prospective associations of accelerometer-measured total sedentary time and breaks in sedentary time with individual cardiometabolic biomarkers in adults ≥18years of age.MethodsOvid Medline, Embase, Web of Science and the Cochrane Library were searched for studies meeting the inclusion criteria. Due to inconsistencies in the measurement and analysis of sedentary time, data was synthesised and presented narratively rather than as a meta-analysis.ResultsTwenty-nine studies were included in the review; twenty-eight reported on total sedentary time and six on breaks in sedentary time. There was consistent evidence from cross-sectional data of an unfavourable association between total sedentary time and insulin sensitivity. There was also some evidence that total sedentary time was unfavourably associated with fasting insulin, insulin resistance and triglycerides. Furthermore, there was some evidence from cross-sectional data of a favourable association between breaks in sedentary time and triglycerides.ConclusionTotal sedentary time was consistently shown to be associated with poorer insulin sensitivity, even after adjusting for time spent in physical activity. This finding supports the proposed association between sedentary time and the development of Type 2 diabetes and reinforces the need to identify interventions to reduce time spent sedentary

The impact of later eating rhythm on childhood adiposity: protocol for a systematic review

Background: Childhood adiposity has increased dramatically in the last few decades and is an important predictor of adulthood chronic disease. Later eating rhythm, termed night eating (NE), is increasingly prevalent in adults; however, the prevalence of NE in children and relationship between NE and adiposity in children still remains uncertain. The aim of this work is to review the association between adiposity in children and adolescents and NE, in terms of calorie intake, timing and meal frequency in the evening/night. Methods: The Cochrane library, CINAHL, Embase, MEDLINE (via OVID) and Web of Science databases will be searched from inception to November 2019 for randomised controlled trials (RCTs) and observational studies (cohort, cross-sectional and case-control studies) which investigate the association between later vs. earlier timing of food intake at night or relatively more vs. less energy intake in any eating occasions or time period after 4 pm on adiposity in children and adolescents (4-18 years). The outcomes will be body mass index (BMI)/BMI standard deviation score (BMI-SDS or BMI Z-score), waist circumference (WC), fat mass index (FMI)/percentage of body fat (%BF) or waist to hip ratio (WHR). No language restriction will be applied. Screening for eligibility from the title and abstracts and data extraction from the full texts will be carried out by two reviewers independently. References listed in the included studies will be hand-searched for any additional articles. The quality of included RCT studies will be assessed using Revised Cochrane Risk of Bias tool (RoB 2), and of observational studies using Newcastle Ottawa scale. A qualitative synthesis of the results will be presented, and meta-analysis will be conducted, where appropriate. Discussion: The planned systematic review will investigate the association between later eating rhythm and adiposity in children and adolescents. Understanding the best meal size, timing of energy intake and meal frequency across the evening time for maintaining healthy weight in children is important in order to give parents the best advice to help prevent adulthood obesity and associated chronic diseases in their children. Systematic review registration: PROSPERO CRD42019134187.</p

Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients.

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time

Dietary interventions for managing glucose abnormalities in cystic fibrosis:a systematic review protocol

Abstract Background Glucose abnormalities in cystic fibrosis (CF) are common, but there is limited evidence to guide their dietary management. Progressive impaired glucose tolerance eventually leads to cystic fibrosis-related diabetes (CFRD), the most prevalent complication of CF, which is associated with increased morbidity and mortality. Optimising glycaemic control improves clinical status and reduces mortality; insulin therapy is the primary means of controlling glycaemia in CFRD, but its role in managing pre-diabetes is less clear. CF dietary therapy requires a high calorie diet due to increased energy expenditure and malabsorption, but this energy-dense diet is typically high in fat and sugar, and high sugar intakes often result in hyperglycaemia in individuals who have impaired glucose handling. Current guidelines for the dietary management of glucose abnormalities in CF are based on clinical consensus rather than empirical evidence. A systematic review conducted in 2012 on the effects of low glycaemic index dietary intervention in CF concluded that there is a dearth of evidence in this area. This review will update the systematic review by Balzer et al. in 2012 and will broaden the scope of their review to include any type of dietary intervention for managing glucose abnormalities in CF. Methods Quantitative studies of dietary interventions to manage glucose abnormalities in individuals aged over 5 years with CF and glucose abnormalities will be reviewed. No limits will be placed on language or study design. The comparator will be standard CF dietary therapy (energy dense, high-fat diet) in addition to insulin therapy for individuals with CFRD. Electronic databases will be searched for completed quantitative studies published in peer-review journals that focus on dietary interventions for managing glucose abnormalities in CF. Searches will be conducted from 2000 up to the present day to reflect the evolving improvements in CF management. No restrictions will be placed on study design or language. Duration of the dietary intervention must be a minimum of 2 months and only interventions in out-patient or community settings will be included. Studies must report on dietary intervention, glycaemic control, anthropometry and lung function. Evidence will be assessed for heterogeneity and a narrative review or meta-analysis conducted as appropriate. Discussion This systematic review will elucidate current knowledge of the effects of dietary interventions for managing glucose abnormalities in the vulnerable CF clinical population. Systematic review registration PROSPERO registration number: CRD42018085569 www.crd.york.ac.uk/prospero

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

Neurophysiological consequences of synapse loss in progressive supranuclear palsy

Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. We advocate that biophysical models of neurophysiology offer both a bridge from clinical to preclinical models of pathology, and quantitative assays for experimental medicine. Such biophysical models can also disclose hidden neuronal dynamics generating neurophysiological observations like electro- and magneto-encephalography. Here, we augment a biophysically informed mesoscale model of human cortical function by inclusion of synaptic density estimates as captured by [11C]UCB-J positron emission tomography, and provide insights into how regional synapse loss affects neurophysiology. We use the primary tauopathy of progressive supranuclear palsy (Richardson's syndrome) as an exemplar condition, with high clinicopathological correlations. Progressive supranuclear palsy causes a marked change in cortical neurophysiology in the presence of mild cortical atrophy and is associated with a decline in cognitive functions associated with the frontal lobe. Using parametric empirical Bayesian inversion of a conductance-based canonical microcircuit model of magnetoencephalography data, we show that the inclusion of regional synaptic density-as a subject-specific prior on laminar specific neuronal populations-markedly increases model evidence. Specifically, model comparison suggests that a reduction in synaptic density in inferior frontal cortex affects superficial and granular layer glutamatergic excitation. This predicted individual differences in behaviour, demonstrating the link between synaptic loss, neurophysiology, and cognitive deficits. The method we demonstrate is not restricted to progressive supranuclear palsy or the effects of synaptic loss: such pathology-enriched dynamic causal models can be used to assess the mechanisms of other neurological disorders, with diverse non-invasive measures of pathology, and is suitable to test the effects of experimental pharmacology