The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small ...molecules such as drugs. In microfluidic devices like “Organs-on-Chip”, designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS.
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•Binding of different compounds to PDMS varies greatly.•Previous reported correlations of absorption and LogP values could not be repeated.•Topological polar surface area possibly related to compound absorption.•A lipid based coating partially obviates compound absorption.•Presence of cultured cells affects free drug concentration, but less than substrate.
Autism spectrum disorder (ASD) is often grouped with other brain-related phenotypes into a broader category of neurodevelopmental disorders (NDDs). In clinical practice, providers need to decide ...which genes to test in individuals with ASD phenotypes, which requires an understanding of the level of evidence for individual NDD genes that supports an association with ASD. Consensus is currently lacking about which NDD genes have sufficient evidence to support a relationship to ASD. Estimates of the number of genes relevant to ASD differ greatly among research groups and clinical sequencing panels, varying from a few to several hundred. This Roadmap discusses important considerations necessary to provide an evidence-based framework for the curation of NDD genes based on the level of information supporting a clinically relevant relationship between a given gene and ASD.
ABSTRACT We present a search for an electromagnetic counterpart of the gravitational-wave source GW151226. Using the Pan-STARRS1 telescope we mapped out 290 square degrees in the optical iP1 filter, ...starting 11.5 hr after the LIGO information release and lasting for an additional 28 days. The first observations started 49.5 hr after the time of the GW151226 detection. We typically reached sensitivity limits of iP1 = 20.3-20.8 and covered 26.5% of the LIGO probability skymap. We supplemented this with ATLAS survey data, reaching 31% of the probability region to shallower depths of m 19. We found 49 extragalactic transients (that are not obviously active galactic nuclei), including a faint transient in a galaxy at 7 Mpc (a luminous blue variable outburst) plus a rapidly decaying M-dwarf flare. Spectral classification of 20 other transient events showed them all to be supernovae. We found an unusual transient, PS15dpn, with an explosion date temporally coincident with GW151226, that evolved into a type Ibn supernova. The redshift of the transient is secure at z = 0.1747 0.0001 and we find it unlikely to be linked, since the luminosity distance has a negligible probability of being consistent with that of GW151226. In the 290 square degrees surveyed we therefore do not find a likely counterpart. However we show that our survey strategy would be sensitive to NS-NS mergers producing kilonovae at DL 100 Mpc, which is promising for future LIGO/Virgo searches.
Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted ...during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally.
Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value.
Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36).
Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.
We present a search for an electromagnetic counterpart of the gravitational wave source GW151226. Using the Pan-STARRS1 telescope we mapped out 290 square degrees in the optical i_ps filter starting ...11.5hr after the LIGO information release and lasting for a further 28 days. The first observations started 49.5hr after the time of the GW151226 detection. We typically reached sensitivity limits of i_ps = 20.3-20.8 and covered 26.5% of the LIGO probability skymap. We supplemented this with ATLAS survey data, reaching 31% of the probability region to shallower depths of m~19. We found 49 extragalactic transients (that are not obviously AGN), including a faint transient in a galaxy at 7Mpc (a luminous blue variable outburst) plus a rapidly decaying M-dwarf flare. Spectral classification of 20 other transient events showed them all to be supernovae. We found an unusual transient, PS15dpn, with an explosion date temporally coincident with GW151226 which evolved into a type Ibn supernova. The redshift of the transient is secure at z=0.1747 +/- 0.0001 and we find it unlikely to be linked, since the luminosity distance has a negligible probability of being consistent with that of GW151226. In the 290 square degrees surveyed we therefore do not find a likely counterpart. However we show that our survey strategy would be sensitive to NS-NS mergers producing kilonovae at D < 100 Mpc which is promising for future LIGO/Virgo searches.
Using a solid-phase double-antibody radioimmunoassay IgG antibodies to native bovine type II collagen were measured as total IgG and as subclasses of IgG (IgG1, IgG2a, IgG2b, IgG2c ) in arthritic and ...non-arthritic Sprague-Dawley rats. Statistically significant differences were observed between arthritic and non-arthritic animals for IgG1, IgG2a, IgG2b and total IgG. The significance of these results and their possible relevance to the human disease are discussed.
Tarsal osteomyelitis in foals Firth, E C; Goedegebuure, S A; Dik, K J ...
Veterinary record,
1985-Mar-09, Volume:
116, Issue:
10
Journal Article
Peer reviewed
Nine foals with haematogenous osteomyelitis of the tarsal bones were studied clinically, radiologically and pathologically. Clinical examination, including aspiration of articular or periarticular ...effusions in the tarsal area, and radiological study provide definitive diagnosis in most cases.
Native 1 alpha 2 alpha 3 alpha collagen (500 micrograms per rat) was both immunogenic and arthritogenic in Alderley Park rats (46% developed arthritis) but only immunogenic in Sprague-Dawley rats. ...Conversely, native type II collagen (500 micrograms per rat) was immunogenic and arthritogenic in both strains (64% arthritic in Alderley Park strain, 57% arthritic in Sprague-Dawley strain). The inflammatory polyarthritis induced by 1 alpha 2 alpha 3 alpha collagen was similar to that produced by native type II collagen in clinical appearance, time of onset, and histology. Antibodies raised to native bovine type II collagen cross-reacted with native 1 alpha 2 alpha 3 alpha collagen and vice versa. Thus the minor collagen component of cartilage, the 1 alpha 2 alpha 3 alpha collagen, as well as the major collagen component, type II collagen, are immunogenic and arthritogenic in the rat, with strain differences.
Both native type II collagen and rabbit IgG were good immunogens in the rat when emulsified in incomplete Freund's adjuvant but native type I collagen and denatured type II collagen were not. Both ...native type II collagen and rabbit IgG had an enhancing effect upon the production of antibodies to native type I collagen when rats were immunised with a mixture of native type I collagen and either of these immunogens but denatured type II collagen did not have this effect. These immunogens, however, did not enhance the production of antibodies to ovalbumin when emulsified with it. Although both native type II collagen and rabbit IgG showed this enhancing effect with native type I collagen, only rats immunised with native type II collagen or mixtures containing native type II collagen developed arthritis. Thus, a specific immune response to collagen rather than this enhancing effect appears to be necessary for the induction of arthritis.
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