Antioxidant effectiveness of vegetable powders on the lipid and protein oxidative stability of cooked Turkey meat patties : implications for health

Peer reviewedPublisher PD

TRAIL-induced variation of cell signaling states provides nonheritable resistance to apoptosis.

TNFα-related apoptosis-inducing ligand (TRAIL), specifically initiates programmed cell death, but often fails to eradicate all cells, making it an ineffective therapy for cancer. This fractional killing is linked to cellular variation that bulk assays cannot capture. Here, we quantify the diversity in cellular signaling responses to TRAIL, linking it to apoptotic frequency across numerous cell systems with single-cell mass cytometry (CyTOF). Although all cells respond to TRAIL, a variable fraction persists without apoptotic progression. This cell-specific behavior is nonheritable where both the TRAIL-induced signaling responses and frequency of apoptotic resistance remain unaffected by prior exposure. The diversity of signaling states upon exposure is correlated to TRAIL resistance. Concomitantly, constricting the variation in signaling response with kinase inhibitors proportionally decreases TRAIL resistance. Simultaneously, TRAIL-induced de novo translation in resistant cells, when blocked by cycloheximide, abrogated all TRAIL resistance. This work highlights how cell signaling diversity, and subsequent translation response, relates to nonheritable fractional escape from TRAIL-induced apoptosis. This refined view of TRAIL resistance provides new avenues to study death ligands in general

What influenced provision of non-communicable disease healthcare in the Syrian conflict, from policy to implementation? A qualitative study.

BACKGROUND: There has been increasing focus on tackling the growing burden of non-communicable diseases (NCD) in crisis settings. The complex and protracted crisis in Syria is unfolding against a background of increasing NCD burden. This study investigated factors influencing implementation of NCD healthcare in Syria. METHODS: This is a qualitative study, whereby semi-structured interviews were conducted with fourteen humanitarian health staff working on NCD healthcare in Syria. RESULTS: Challenges to NCD care implementation were reflected at several stages, from planning services through to healthcare delivery. There was a lack of information on unmet population need; little consensus among humanitarian actors regarding an appropriate health service package; and no clear approach for prioritising public health interventions. The main challenges to service delivery identified by participants were conflict-related insecurity and disruption to infrastructure, hampering continuity of chronic illness care. Collaboration was a key factor which influenced implementation at all stages. CONCLUSIONS: The historical context, the conflict situation, and the characteristics of health actors and their relationships, all impacted provision of NCD care. These factors influenced each other, so that the social views and values (of individuals and organisations), as well as politics and relationships, interacted with the physical environment and security situation. Infrastructure damage has implications for wider healthcare across Syria, and NCD care requires an innovative approach to improve continuity of care. There is a need for a transparent approach to resource allocation, which may be generalisable to the wider humanitarian health sector

DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity.

An individual malignant tumor is composed of a heterogeneous collection of single cells with distinct molecular and phenotypic features, a phenomenon termed intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for cancer treatment, motivating the need for combination therapies. Single-cell technologies are now available to guide effective drug combinations by accounting for intratumoral heterogeneity through the analysis of the signaling perturbations of an individual tumor sample screened by a drug panel. In particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single-cell technology that enables the simultaneous measurements of multiple ([Formula: see text]40) intracellular and surface markers at the level of single cells for hundreds of thousands of cells in a sample. We developed a computational framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF single-drug perturbation data for the purpose of individualizing drug combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number of drugs that produce the maximal desired intracellular effects based on nested effects modeling. We demonstrate the performance of DRUG-NEM using single-cell drug perturbation data from tumor cell lines and primary leukemia samples

Defining, measuring and interpreting the appropriateness of humanitarian assistance

This paper presents findings from a literature review of methods that explicitly assess the appropriateness of a humanitarian response. We set out to highlight the key features and limitations of each method and introduce a definition and conceptual framework for the measurement and interpretation of the appropriateness of humanitarian responses. This review is part of a broader project to enhance the accountability of humanitarian responses through developing auditing approaches for real-time monitoring. We identified eight methods that explicitly analyse the appropriateness of a humanitarian response. The review revealed that existing methods vary considerably in their definitions of ‘appropriateness’, provide insufficient guidance on measurement, are vulnerable to interpretive bias and frequently report findings on ‘appropriateness’ in an ambiguous manner. These findings suggest that, as a matter of accountability, more structured and systematic approaches to measuring the appropriateness of humanitarian response are needed. We propose a definition and conceptual framework for the measurement and interpretation of the appropriateness of humanitarian response that seeks to address the limitations identified in the review. We provide a brief overview of the main components and features of a systematic approach and audit tool for assessing the ‘appropriateness’ of a humanitarian response. The use of this and other systematic approaches is essential for enhancing governance and accountability in humanitarian responses

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

Delivering a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: a descriptive costing study.

The Syrian conflict has caused enormous displacement of a population with a high non-communicable disease (NCD) burden into surrounding countries, overwhelming health systems' NCD care capacity. Médecins sans Frontières (MSF) developed a primary-level NCD programme, serving Syrian refugees and the host population in Irbid, Jordan, to assist the response. Cost data, which are currently lacking, may support programme adaptation and system scale up of such NCD services. This descriptive costing study from the provider perspective explored financial costs of the MSF NCD programme. We estimated annual total, per patient and per consultation costs for 2015-17 using a combined ingredients-based and step-down allocation approach. Data were collected via programme budgets, facility records, direct observation and informal interviews. Scenario analyses explored the impact of varying procurement processes, consultation frequency and task sharing. Total annual programme cost ranged from 4 to 6 million International Dollars (INT$), increasing annually from INT$4 206 481 (2015) to INT$6 739 438 (2017), with costs driven mainly by human resources and drugs. Per patient per year cost increased 23$1424 (2015) to 1751 (2016), and by 9% to 1904 (2017), while cost per consultation increased from INT$209 to 253 (2015-17). Annual cost increases reflected growing patient load and increasing service complexity throughout 2015-17. A scenario importing all medications cut total costs by 31%, while negotiating importation of high-cost items offered 13% savings. Leveraging pooled procurement for local purchasing could save 20%. Staff costs were more sensitive to reducing clinical review frequency than to task sharing review to nurses. Over 1000 extra patients could be enrolled without additional staffing cost if care delivery was restructured. Total costs significantly exceeded costs reported for NCD care in low-income humanitarian contexts. Efficiencies gained by revising procurement and/or restructuring consultation models could confer cost savings or facilitate cohort expansion. Cost effectiveness studies of adapted models are recommended

Complete Ascertainment of Intragenic Copy Number Mutations (CNMs) in the CFTR Gene and its Implications for CNM Formation at Other Autosomal Loci

Over the last 20 years since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, more than 1,600 different putatively pathological CFTR mutations have been identified. Until now, however, copy number mutations (CNMs) involving the CFTR gene have not been methodically analyzed, resulting almost certainly in the under-ascertainment of CFTR gene duplications compared with deletions. Here, high-resolution array comparative genomic hybridization (averaging one interrogating probe every 95 bp) was used to analyze the entire length of the CFTR gene (189 kb) in 233 cystic fibrosis chromosomes lacking conventional mutations. We succeeded in identifying five duplication CNMs that would otherwise have been refractory to analysis. Based upon findings from this and other studies, we propose that deletion and duplication CNMs in the human autosomal genome are likely to be generated in the proportion of approximately 2-3:1. We further postulate that intragenic gene duplication CNMs in other disease loci may have been routinely underascertained. Finally, our analysis of +/-20 bp flanking each of the 40 CFTR breakpoints characterized at the DNA sequence level provide support for the emerging concept that non-B DNA conformations in combination with specific sequence motifs predispose to both recurring and nonrecurring genomic rearrangements. Hum Mutat 31:421-428, 2010. (C) 2010 Wiley-Liss, Inc

Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line

The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge for understanding biological changes ranging from cellular differentiation to epigenetic responses of diseased cells upon drugging. We integrate experiments and theory to determine the trajectories that single BRAF^(V600E) mutant melanoma cancer cells take between drug-naive and drug-tolerant states. Although single-cell omics tools can yield snapshots of the cell-state landscape, the determination of individual cell trajectories through that space can be confounded by stochastic cell-state switching. We assayed for a panel of signaling, phenotypic, and metabolic regulators at points across 5 days of drug treatment to uncover a cell-state landscape with two paths connecting drug-naive and drug-tolerant states. The trajectory a given cell takes depends upon the drug-naive level of a lineage-restricted transcription factor. Each trajectory exhibits unique druggable susceptibilities, thus updating the paradigm of adaptive resistance development in an isogenic cell population