Pre-operative optimisation for chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is a condition commonly present in older people undergoing surgery and confers an increased risk of postoperative complications and mortality. Although predominantly a respiratory disease, it frequently has extra‐pulmonary manifestations and typically occurs in the context of other long‐term conditions. Patients experience a range of symptoms that affect their quality of life, functional ability and clinical outcomes. In this review, we discuss the evidence for techniques to optimise the care of people with chronic obstructive pulmonary disease in the peri‐operative period, and address potential new interventions to improve outcomes. The article centres on pulmonary rehabilitation, widely available for the treatment of stable chronic obstructive pulmonary disease, but less often used in a peri‐operative setting. Current evidence is largely at high risk of bias, however. Before surgery it is important to ensure that what have been called the ‘five fundamentals’ of chronic obstructive pulmonary disease treatment are achieved: smoking cessation; pulmonary rehabilitation; vaccination; self‐management; and identification and optimisation of co‐morbidities. Pharmacological treatment should also be optimised, and some patients may benefit from lung volume reduction surgery. Psychological and behavioural factors are important, but are currently poorly understood in the peri‐operative period. Considerations of the risk and benefits of delaying surgery to ensure the recommended measures are delivered depends on patient characteristics and the nature and urgency of the planned intervention

Supporting the family as a whole: a needs assessment study on Cancer Families in Hong Kong

Powerpoint presentationConference Theme: East meets West: Expanding Frontiers and Diversitypublished_or_final_versio

Simultaneous Genome-Wide Inference of Physical, Genetic, Regulatory, and Functional Pathway Components

Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactions and modifications to indirect regulatory relationships. One goal of systems biology is to bridge three aspects of this complexity: the growing body of high-throughput data assaying these interactions; the specific interactions in which individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data. This results in a comprehensive compendium of whole-genome networks for yeast, derived from ∼3,500 experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory) to specific (e.g. phosphorylation or transcriptional regulation). We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel connection between glycogen breakdown and glucose utilization supported by recent publications. Additionally, 14 specific predicted interactions in DNA topological change and protein biosynthesis were experimentally validated. We analyzed the systems-level network features within all interactomes, verifying the presence of small-world properties and enrichment for recurring network motifs. This compendium of physical, synthetic, regulatory, and functional interaction networks has been made publicly available through an interactive web interface for investigators to utilize in future research at http://function.princeton.edu/bioweaver/

A Phenome-Based Functional Analysis of Transcription Factors in the Cereal Head Blight Fungus, Fusarium graminearum

Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops. The fungus produces mycotoxins that are harmful to animal and human. In this study, a systematic analysis of 17 phenotypes of the mutants in 657 Fusarium graminearum genes encoding putative transcription factors (TFs) resulted in a database of over 11,000 phenotypes (phenome). This database provides comprehensive insights into how this cereal pathogen of global significance regulates traits important for growth, development, stress response, pathogenesis, and toxin production and how transcriptional regulations of these traits are interconnected. In-depth analysis of TFs involved in sexual development revealed that mutations causing defects in perithecia development frequently affect multiple other phenotypes, and the TFs associated with sexual development tend to be highly conserved in the fungal kingdom. Besides providing many new insights into understanding the function of F. graminearum TFs, this mutant library and phenome will be a valuable resource for characterizing the gene expression network in this fungus and serve as a reference for studying how different fungi have evolved to control various cellular processes at the transcriptional level

The Information Coded in the Yeast Response Elements Accounts for Most of the Topological Properties of Its Transcriptional Regulation Network

The regulation of gene expression in a cell relies to a major extent on transcription factors, proteins which recognize and bind the DNA at specific binding sites (response elements) within promoter regions associated with each gene. We present an information theoretic approach to modeling transcriptional regulatory networks, in terms of a simple “sequence-matching” rule and the statistics of the occurrence of binding sequences of given specificity in random promoter regions. The crucial biological input is the distribution of the amount of information coded in these cognate response elements and the length distribution of the promoter regions. We provide an analysis of the transcriptional regulatory network of yeast Saccharomyces cerevisiae, which we extract from the available databases, with respect to the degree distributions, clustering coefficient, degree correlations, rich-club coefficient and the k-core structure. We find that these topological features are in remarkable agreement with those predicted by our model, on the basis of the amount of information coded in the interaction between the transcription factors and response elements

A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis

Using small molecule probes to understand gene function is an attractive approach that allows functional characterization of genes that are dispensable in standard laboratory conditions and provides insight into the mode of action of these compounds. Using chemogenomic assays we previously identified yeast Crg1, an uncharacterized SAM-dependent methyltransferase, as a novel interactor of the protein phosphatase inhibitor cantharidin. In this study we used a combinatorial approach that exploits contemporary high-throughput techniques available in Saccharomyces cerevisiae combined with rigorous biological follow-up to characterize the interaction of Crg1 with cantharidin. Biochemical analysis of this enzyme followed by a systematic analysis of the interactome and lipidome of CRG1 mutants revealed that Crg1, a stress-responsive SAM-dependent methyltransferase, methylates cantharidin in vitro. Chemogenomic assays uncovered that lipid-related processes are essential for cantharidin resistance in cells sensitized by deletion of the CRG1 gene. Lipidome-wide analysis of mutants further showed that cantharidin induces alterations in glycerophospholipid and sphingolipid abundance in a Crg1-dependent manner. We propose that Crg1 is a small molecule methyltransferase important for maintaining lipid homeostasis in response to drug perturbation. This approach demonstrates the value of combining chemical genomics with other systems-based methods for characterizing proteins and elucidating previously unknown mechanisms of action of small molecule inhibitors

The development, implementation and evaluation of interventions to reduce workplace sitting: a qualitative systematic review and evidence-based operational framework

Background: Prolonged sitting is associated with increased risks of cardiovascular disease, Type 2 diabetes, some cancers, musculoskeletal disorders and premature mortality. Workplaces contribute to a large proportion of daily sitting time, particularly among office-based workers. Interventions to reduce workplace sitting therefore represent important public health initiatives. Previous systematic reviews suggest such interventions can be effective but have reported wide variations. Further, there is uncertainty as to whether effectiveness in controlled trials can be replicated when implemented outside the research setting. The aims of this review are to identify factors important for the implementation of workplace sitting interventions and to translate these findings into a useful operational framework to support the future implementation of such interventions. Methods: A qualitative systematic review was conducted. Four health and social science databases were searched for studies set in the workplace, with office-based employees and with the primary aim of reducing workplace sitting. Extracted data were primarily from author descriptions of interventions and their implementation. Inductive thematic analysis and synthesis was undertaken. Results: Forty studies met the inclusion criteria. Nine descriptive themes were identified from which emerged three higher-order analytical themes, which related to the development , implementation and evaluation of workplace sitting interventions. Key findings inc luded: the importance of groundi ng interventions in theory; utilising participative approaches during intervention development and implementation; and c onducting comprehensive proce ss and outcome evaluations. There was a general under-reporting of info rmation relating to the context within which workplace sitting interventions were implemented, such as details of local organisation processes and structures, as well as the wider political and economic landscape, which if present would aid the translation of knowledge into “ real-world ” settings. Conclusions: These findings provided the basis for an operational framework, which is a representation of all nine descriptive themes and three higher-order analytical themes, to support workplace sitting intervention development, implementation and evaluation. Once tested and refined, this framework has the potential to be incorporated into a practical toolkit, which could be used by a range of organisations to develop, implement and evaluate their own interventions to reduce workplace sitting time amongst staff

Endurance performance is influenced by perceptions of pain and temperature: Theory, applications and safety considerations.

Models of endurance performance now recognise input from the brain, including an athlete’s ability to cope with various non-pleasurable perceptions during exercise, such as pain and temperature. Exercise training can reduce perceptions of both pain and temperature over time, partly explaining why athletes generally have a higher pain tolerance, despite a similar pain threshold, compared with active controls. Several strategies with varying efficacy may ameliorate the perceptions of pain (e.g. acetaminophen, transcranial direct current stimulation and transcutaneous electrical stimulation) and temperature (e.g. menthol beverages, topical menthol products and other cooling strategies, especially those targeting the head) during exercise to improve athletic performance. This review describes both the theory and practical applications of these interventions in the endurance sport setting, as well as the potentially harmful health consequences of their use