Fluorescent α-amino acids via Heck-Matsuda reactions of phenylalanine-derived arenediazonium salts.

The Heck-Matsuda coupling reaction of arenediazonium salts derived from L-phenylalanine with various alkenes has been developed. A two-step process involving the preparation of a tetrafluoroborate diazonium salt from a 4-aminophenylalanine derivative, followed by a palladium(0)-catalysed Heck-Matsuda coupling reaction allowed access to a range of unnatural α-amino acids with cinnamate, vinylsulfone and stilbene side-chains. Analysis of the photophysical properties of these unnatural α-amino acids demonstrated that the (E)-stilbene analogues exhibited fluorescent properties with red-shifted absorption and emission spectra and larger quantum yields than L-phenylalanine.

Synthesis of ß-Pyridyl α-Amino Acids: Conformationally Sensitive Charge Transfer-Based Fluorophores.

Unnatural α-amino acids with charge transfer-based poly aromatic side chains have been designed as conformationally sensitive fluorophores. These were prepared using a hetero-Diels-Alder reaction and a Knoevenagel-Stobbe process to generate a biaryl pyridyl unit, followed by iron-catalyzed bromination and a Suzuki-Miyaura cross-coupling reaction to complete the triaryl system. A photophysical study led to the discovery of a p-methoxy analogue which exhibited viscosity-sensitive fluorescence in which emission could be controlled between twisted and planar conformations.

Transferring Micellar Changes to Bulk Properties via Tunable Self-Assembly and Hierarchical Ordering.

Hierarchical self-assembly is an effective means of preparing useful materials. However, control over assembly across length scales is a difficult challenge, often confounded by the perceived need to redesign the molecular building blocks when new material properties are needed. Here, we show that we can treat a simple dipeptide building block as a polyelectrolyte and use polymer physics approaches to explain the self-assembly over a wide concentration range. This allows us to determine how entangled the system is and therefore how it might be best processed, enabling us to prepare interesting analogues to threads and webs, as well as films that lose order on heating and "noodles" which change dimensions on heating, showing that we can transfer micellar-level changes to bulk properties all from a single building block.

Risk messages relating to fertility and pregnancy: a media content analysis.

Background: The UK print and online media is an important channel by which scientific research is communicated to the public. Media risk messages relating to pregnancy or fertility contribute to the context of reproductive decision making, but their fidelity to the underlying science has been questioned. Method: We measured the volume, distribution and content of science-based risk headlines relating to pregnancy or fertility in the UK media over four months. We grouped headlines into unique stories and categorised them by exposure and outcome of interest. We selected four unique stories for closer content analysis and assessed their fidelity to the underlying science, with attention to the role of press releases. Results: We identified 171 headlines over four months (average 43 per month), comprising 56 unique stories. The unique stories most commonly concerned maternal risk factors (n=46) and child health outcomes (n=46). Maternal health outcomes were less frequently the focus (n=20). The most common risk factors in the media coverage were maternal food and drink (n=15), maternal medication and medical interventions (n=9), and maternal health factors (n=6). Media reports were largely faithful to press releases. Where substantive deviations from the underlying scientific study were identified, these could mostly be traced back to press releases or quotes from the study's authors. Press releases often omitted caveats which were reinstated at the media reporting stage, alongside additional expert criticism. Conclusions: Frequent science-based risk messages in the UK media frame mothers as vectors of potential harm to children, who are the focus of health outcomes. Largely, the media does not introduce misinformation, but reports press releases faithfully with additional caveats and expert commentary. Press releases fulfil an interpretative role, often omitting caveats and introducing new elements and advice to women. Their role as a bridge between scientific and lay audiences is discussed.

Mitochondrial C5aR1 activity in macrophages controls IL-1ß production underlying sterile inflammation.

While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the "complosome," functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular complement is also nonredundant for the activity of myeloid immune cells is currently unknown. Here, we show that monocytes and macrophages constitutively express complement component (C) 5 and generate autocrine C5a via formation of an intracellular C5 convertase. Cholesterol crystal sensing by macrophages induced C5aR1 signaling on mitochondrial membranes, which shifted ATP production via reverse electron chain flux toward reactive oxygen species generation and anaerobic glycolysis to favor IL-1ß production, both at the transcriptional level and processing of pro­IL-1ß. Consequently, atherosclerosis-prone mice lacking macrophage-specific C5ar1 had ameliorated cardiovascular disease on a high-cholesterol diet. Conversely, inflammatory gene signatures and IL-1ß produced by cells in unstable atherosclerotic plaques of patients were normalized by a specific cell-permeable C5aR1 antagonist. Deficiency of the macrophage cell-autonomous C5 system also protected mice from crystal nephropathy mediated by folic acid. These data demonstrate the unexpected intracellular formation of a C5 convertase and identify C5aR1 as a direct modulator of mitochondrial function and inflammatory output from myeloid cells. Together, these findings suggest that the complosome is a contributor to the biologic processes underlying sterile inflammation and indicate that targeting this system could be beneficial in macrophage-dependent diseases, such as atherosclerosis.

Predicting 30- to 120-Day Readmission Risk among Medicare Fee-for-Service Patients Using Nonmedical Workers and Mobile Technology.

OBJECTIVE: Hospital readmissions are a large source of wasteful healthcare spending, and current care transition models are too expensive to be sustainable. One way to circumvent cost-prohibitive care transition programs is complement nurse-staffed care transition programs with those staffed by less expensive nonmedical workers. A major barrier to utilizing nonmedical workers is determining the appropriate time to escalate care to a clinician with a wider scope of practice. The objective of this study is to show how mobile technology can use the observations of nonmedical workers to stratify patients on the basis of their hospital readmission risk. MATERIALS AND METHODS: An area agency on aging in Massachusetts implemented a quality improvement project with the aim of reducing 30-day hospital readmission rates using a modified care transition intervention supported by mobile predictive analytics technology. Proprietary readmission risk prediction algorithms were used to predict 30-, 60-, 90-, and 120-day readmission risk. RESULTS: The risk score derived from the nonmedical workers' observations had a significant association with 30-day readmission rate with an odds ratio (OR) of 1.12 (95 percent confidence interval [CI], 1 .09-1.15) compared to an OR of 1.25 (95 percent CI, 1.19-1.32) for the risk score using nurse observations. Risk scores using nurse interpretation of nonmedical workers' observations show that patients in the high-risk category had significantly higher readmission rates than patients in the baseline-risk and mild-risk categories at 30, 60, 90, and 120 days after discharge. Of the 1,064 elevated-risk alerts that were triaged, 1,049 (98.6 percent) involved the nurse care manager, 804 (75.6 percent) involved the patient, 768 (72.2 percent) involved the health coach, 461 (43.3 percent) involved skilled nursing, and 235 (22.1 percent) involved the outpatient physician in the coordination of care in response to the alert. DISCUSSION: The predictive nature of the 30-day readmission risk scores is influenced by both nurse and nonmedical worker input, and both are required to adequately triage the needs of the patient. CONCLUSION: Although this preliminary study is limited by a modest effect size, it demonstrates one approach to using technology to contribute to delivery model innovation that could curb wasteful healthcare spending by tapping into an existing underutilized workforce.