Stress, illness perceptions, behaviours and healing in venous leg ulcers: findings from a prospective observational study

Objective: To investigate the impact of stress, illness perceptions and behaviours on healing of venous leg ulcers. Methods: A prospective observational study of 63 individuals for 24 weeks investigated possible psychosocial predictors of healing. There were two indices of healing: rate of change in ulcer area and number of weeks to heal. Psychological variables were assessed at baseline using self-report measures (Perceived Stress Scale, Hospital Anxiety and Depression Scale, Revised Illness Perception Questionnaire, adapted Summary of Diabetes Self-Care Activities, Adherence Questionnaire and Short-Form Health Survey). Results: Controlling for socio-demographic and clinical variables, over the 24 weeks a slower rate of change in ulcer area was predicted by greater stress (standardised beta =-0.61, p=0.008); depression (standardised beta =-0.51, p=0.039); holding negative perceptions or beliefs about the ulcer (standardised beta =-1.4, p=0.045). By 24 weeks 69% of ulcers had closed. A more negative emotional response to the ulcer at baseline, (i.e., emotional representation of the ulcer), was associated with a greater number of weeks to heal [Hazard Ratio (HR) = 0.63, 95% CI 0.41 - 0.95, p=0.028]. Higher educational attainment (HR= 3.22, 95% CI 1.37 - 7.55, p=0.007) and better adherence to compression bandaging (HR= 1.41 95% CI 1.06 - 1.88, p=0.019) were associated with fewer weeks to heal. No other psychosocial variable (stress; perceptions about the ulcer; health behaviours) predicted weeks to heal. Conclusions: Alongside ulcer-related predictors, psychological and sociodemographic factors were associated with healing. Future research should explore mediating mechanisms underlying these associations and develop interventions to target these variables

Does Testosterone Mediate the Relationship Between Vitamin D and Prostate Cancer? A Systematic Review and Meta-Analysis Protocol

Abstract Background Evidence from studies on prostate cancer progression have identified vitamin D to be a potentially important nutrient. However, the World Cancer Research Fund and American Institute for Cancer Research have reported the quality of this evidence to be limited and warrant further investigation. We plan to use the recently developed WCRF International/University of Bristol mechanistic systematic review framework to determine whether the observed association between vitamin D and prostate cancer exists through a plausible biological pathway. Methods This protocol sets out how we will perform a systematic review of the literature in human and animal studies. We will search the electronic databases MEDLINE, EMBASE, PubMed, and BIOSIS Citation Index without restrictions on year of publication or language. We will extract data from observational and experimental studies examining two inter-linked pathways in the relationship between vitamin D and prostate cancer progression: (1) vitamin D and testosterone, and (2) testosterone and prostate cancer progression. We focus on testosterone as its actions form a potentially novel intermediate mechanism that was identified via our online literature mining tools. The outcomes of interest include incidence or prevalence of prostate cancer, measures of prostate cancer progression (including biochemical recurrence, local, or distal metastases), and prostate cancer-specific mortality. We will assess study quality and the level of certainty of the evidence. We will analyse data where possible, using meta-analysis with forest plots or albatross plots; otherwise, a narrative synthesis will be performed. Discussion To our knowledge, this will be the first systematic synthesis of the evidence underpinning the vitamin D-testosterone-prostate cancer mechanistic pathway. The results of the review may inform future research, intervention trials, and public health messages

Ring-opening polymerization of rac-lactide mediated by tetrametallic lithium and sodium diamino-bis(phenolate) complexes

Lithium and sodium compounds supported by tetradentate amino-bis(phenolato) ligands, [Li2(N2O2BuBuPip)] (1), [Na2(N2O2BuBuPip)] (2) (where [N2O2BuBuPip] = 2,2′-N,N’-homopiperazinyl-bis(2-methylene-4,6-tert-butylphenol), and [Li2(N2O2BuMePip)] (3), [Na2(N2O2BuMePip)] (4) (where [N2O2BuMePip] = 2,2′-N,N’-homopiperazinyl-bis(2-methylene-4-methyl-6-tert-butylphenol) were synthesized and characterized by NMR spectroscopy and MALDI-TOF mass spectrometry. Variable temperature NMR experiments were performed to understand solution-phase dynamics. The solid-state structures of 1 and 4 were determined by X-ray diffraction and reveal tetrametallic species. PGSE NMR spectroscopic data suggests that 1 maintains its aggregated structure in CD2Cl2. The complexes exhibit good activity for controlled ring-opening polymerization of rac-lactide (LA) both solvent free and in solution to yield PLA with low dispersities. Stoichiometric reactions suggest that the formation of PLA may proceed by the typical coordination–insertion mechanism. For example, 7Li NMR experiments show growth of a new resonance when 1 is mixed with 1 equiv. LA and 1H NMR data suggests formation of a Li-alkoxide species upon reaction of 1 with BnOH

MELODI:Mining Enriched Literature Objects to Derive Intermediates

Background: The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis. Methods: Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts. Results: Two case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Second, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studied in vitro. Conclusions: We have demonstrated the possible applications of MELODI, including two case studies. MELODI has been implemented as a Python/Django web application, and is freely available to use at [www.melodi.biocompute.org.uk]

A standardized kinesin nomenclature

In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered

The North American tree-ring fire-scar network

Fire regimes in North American forests are diverse and modern fire records are often too short to capture important patterns, trends, feedbacks, and drivers of variability. Tree-ring fire scars provide valuable perspectives on fire regimes, including centuries-long records of fire year, season, frequency, severity, and size. Here, we introduce the newly compiled North American tree-ring fire-scar network (NAFSN), which contains 2562 sites, >37,000 fire-scarred trees, and covers large parts of North America. We investigate the NAFSN in terms of geography, sample depth, vegetation, topography, climate, and human land use. Fire scars are found in most ecoregions, from boreal forests in northern Alaska and Canada to subtropical forests in southern Florida and Mexico. The network includes 91 tree species, but is dominated by gymnosperms in the genus Pinus. Fire scars are found from sea level to >4000-m elevation and across a range of topographic settings that vary by ecoregion. Multiple regions are densely sampled (e.g., >1000 fire-scarred trees), enabling new spatial analyses such as reconstructions of area burned. To demonstrate the potential of the network, we compared the climate space of the NAFSN to those of modern fires and forests; the NAFSN spans a climate space largely representative of the forested areas in North America, with notable gaps in warmer tropical climates. Modern fires are burning in similar climate spaces as historical fires, but disproportionately in warmer regions compared to the historical record, possibly related to under-sampling of warm subtropical forests or supporting observations of changing fire regimes. The historical influence of Indigenous and non-Indigenous human land use on fire regimes varies in space and time. A 20th century fire deficit associated with human activities is evident in many regions, yet fire regimes characterized by frequent surface fires are still active in some areas (e.g., Mexico and the southeastern United States). These analyses provide a foundation and framework for future studies using the hundreds of thousands of annually- to sub-annually-resolved tree-ring records of fire spanning centuries, which will further advance our understanding of the interactions among fire, climate, topography, vegetation, and humans across North America