Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.

Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.

Serum triamcinolone levels during intensive, inpatient wet-dressing therapy.

BACKGROUND: Wet dressings combined with topical corticosteroids are beneficial for patients with generalized and refractory dermatosis; however, to our knowledge, serum levels after topical corticosteroid absorption during intensive therapy have not been reported previously. AIM: To examine serum levels of triamcinolone acetonide (TAC) after topical corticosteroid application during intensive wet-dressing therapy. METHODS: We performed a retrospective study of adult patients admitted for inpatient wet-dressing therapy from 7 November 2015 to 24 June 2016. Data were collected on sex, age, body surface area, TAC serum levels, number of wet-dressing changes after 24 and 48 h, and type of wet dressing. RESULTS: In total, 29 patients (14 men, 15 women) were assessed. Median [interquartile range (IQR)] age was 57 years (51.5-67.0 years) and involved body surface area was 1.98 m2 (1.88-2.15) m2 . Before the 24-hour blood draw, patients had received 1-3 dressing changes. Median (IQR) TAC level at 24 h was 0.33 µg/dL (0.20-0.58 µg/dL), with no significant difference noted between the number of dressing changes and TAC serum level. At 48 h, results of a serum TAC test were available for 22 patients with 2-6 dressing changes. Mean (IQR) serum level was 0.30 µg/dL (0.30-0.87 µg/dL). For each additional dressing change, there was an estimated 0.21 µg/dL increase in TAC serum level (95% CI 0.11-0.31; P < 0.001). TAC serum level was not significantly associated with sex, age, body surface area or dressing type. CONCLUSIONS: Intensive, inpatient wet-dressing therapy is associated with detectable TAC serum levels. However, we suspect that topical TAC has a primarily local therapeutic effect on the skin.

The reporting of mental disorders research in British media.

BACKGROUND: While the media may significantly influence public attitudes and government policies affecting the research agenda, how mental health research is reported in the media has been virtually unstudied. The aim of this study was to examine stories concerning mental health research published on the British Broadcasting Corporation (BBC) website between 1999 and 2008 and in New Scientist between 2008 and 2010. METHOD: Stories were retrieved from on-line archives. Story content was coded and assessed against: 'disease burden' of mental disorders; the general corpus of research papers in mental health and the countries from which they originated; the journals in which cited papers were published; and funding sources. RESULTS: A total of 1015 BBC stories reporting mental health research and 133 New Scientist stories were found. The distribution of stories did not reflect 'disease burden'; research on dementia was over-represented, while depression and alcohol were under-represented. There was an emphasis on biological research while stories on psychological interventions were rare. UK research was over-represented. Research funded by government and private non-profit sources was over-represented. Commentators from Alzheimer's Disease charities were prominent. CONCLUSIONS: Consideration of reported stories may suggest approaches to working with the media to improve the public understanding of, and support for, mental health research. The role of commentators may be especially important.

Antibody catalysis of the oxidation of water.

Recently we reported that antibodies can generate hydrogen peroxide (H2O2) from singlet molecular oxygen (1O2*). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H2O2. Antibodies produce up to 500 mole equivalents of H2O2 from 1O2*, without a reduction in rate, and we have excluded metals or Cl- as the electron source. On the basis of isotope incorporation experiments and kinetic data, we propose that antibodies use H2O as an electron source, facilitating its addition to 1O2* to form H2O3 as the first intermediate in a reaction cascade that eventually leads to H2O2. X-ray crystallographic studies with xenon point to putative conserved oxygen binding sites within the antibody fold where this chemistry could be initiated. Our findings suggest a protective function of immunoglobulins against 1O2* and raise the question of whether the need to detoxify 1O2* has played a decisive role in the evolution of the immunoglobulin fold.

Antibodies have the intrinsic capacity to destroy antigens.

Research throughout the last century has led to a consensus as to the strategy of the humoral component of the immune system. The essence is that, for killing, the antibody molecule activates additional systems that respond to antibody-antigen union. We now report that the immune system seems to have a previously unrecognized chemical potential intrinsic to the antibody molecule itself. All antibodies studied, regardless of source or antigenic specificity, can convert molecular oxygen into hydrogen peroxide, thereby potentially aligning recognition and killing within the same molecule. Aside from pointing to a new chemical arm for the immune system, these results may be important to the understanding of how antibodies evolved and what role they may play in human diseases.

A one-pot multistep approach to alpha-azido-phosphonate and phosphonothioate diesters: key intermediates in the synthesis of haptens for the generation of antibody ligases.

A four-step, one-pot synthesis of mixed alpha-azido-phosphonates and phosphonothioates 12a-d is described. This chemistry has provided a facile route to haptens 6a b and 7 that have been employed for the elicitation of antibody ligases. Five hapten-specific antibodies have been identified as modest catalysts of a model peptide ligation reaction between thioester 1b and thiol 2 to give the amide product 5.

A soluble polymer-supported triflating reagent: a high-throughput synthetic approach to aryl and enol triflates.

[reaction: see text] The high-yielding synthesis and application of the first example of a polymer-supported reagent for the preparation of trifluoromethanesulfonates (triflates) is described. This new reagent efficiently triflates aryl alcohols and lithium enolates in high yield (>90%). A simple precipitation and filtration to remove the excess reagent and byproduct facilitate purification of the triflate products. The PEG-supported approach is highly efficient, as the PEG-supported byproduct can be quantitatively recovered and recycled into reagent 1.

A bait and switch hapten strategy generates catalytic antibodies for phosphodiester hydrolysis.

General base catalysis supplied by the histidine-12 (H-12) residue of ribonuclease (RNase) A has long been appreciated as a major component of the catalytic power of the enzyme. In an attempt to harness the catalytic power of a general base into antibody catalysis of phosphodiester bond hydrolysis, the quaternary ammonium phosphate 1 was used as a bait and switch hapten. Based on precedence, it was rationalized that this positively charged hapten could induce a counter-charged residue in the antibody binding site at a locus suitable for it to deprotonate the 2'-hydroxyl group of the anhydroribitol phosphodiester substrate 2. After murine immunization with hapten 1, mAb production yielded a library of 35 antibodies that bound to a BSA-1 conjugate. From this panel, two were found to catalyze the cyclization-cleavage of phosphodiester 2. Kinetic studies at pH 7.49 (Hepes, 20 mM) and 25 degreesC showed that the most active antibody, MATT.F-1, obeyed classical Michaelis-Menten kinetics with a Km = 104 microM, a kcat = 0.44 min-1, and a kcat/kuncat = 1.7 x 10(3). Hapten 1 stoichiometrically inhibits the catalytic activity of the antibody. MATT.F-1 is the most proficient antibody-catalyst (1.6 x 10(7) M-1) yet generated for the function of phosphodiester hydrolysis and emphasizes the utility of the bait and switch hapten paradigm when generating antibody catalysts for processes for which general-base catalysis can be exploited.