Association between ethnicity and migration status with the prevalence of single and multiple long-term conditions in UK healthcare workers

No description supplie

The Use of Synchrotron X-rays To Observe Copper Corrosion in Real Time

We have developed and tested two complementary methods for making time-lapse synchrotron X-ray diffraction (XRD) measurements of the growth of synthetic corrosion layers using a protocol for producing copper­(I) chloride (nantokite), on copper as a test. In the first method, a copper coupon was spin-coated with saturated copper­(II) chloride solution in air while the surface was characterized in real time using XRD with a fast one-dimensional (1-D) detector. In the second, a droplet of the same reagent was suspended from an X-ray-transparent window in a hermetically sealed cell and the coupon was brought into contact with this while XRD diffractograms were acquired with a charge-coupled device (CCD) camera. The protocol is completed by a deionized water rinse, which was also studied. The XRD shows nantokite precipitation in solution as well as growth on the surface, but the end products were variable proportions of nantokite, cuprite (Cu₂O), and paratacamite (Cu₂(OH)₃Cl). The latter two were observed forming in a reaction between the nantokite and the rinsing water. Comparisons between samples analyzed in the synchrotron and at lower power densities show that the effects of any radiolysis or slight heating of the sample are insignificant in this case. It would be simple to extend these methods to other corrosion or surface reaction systems

High-Content Microfluidic Screening Platform Used To Identify σ2R/Tmem97 Binding Ligands that Reduce Age-Dependent Neurodegeneration in <i>C. elegans</i> SC_APP Model

The nematode <i>Caenorhabditis elegans</i>, with tractable genetics and a well-defined nervous system, provides a unique whole-animal model system to identify novel drug targets and therapies for neurodegenerative diseases. Large-scale drug or target screens in models that recapitulate the subtle age- and cell-specific aspects of neurodegenerative diseases are limited by a technological requirement for high-throughput analysis of neuronal morphology. Recently, we developed a single-copy model of amyloid precursor protein (SC_APP) induced neurodegeneration that exhibits progressive degeneration of select cholinergic neurons. Our previous work with this model suggests that small molecule ligands of the sigma 2 receptor (σ2R), which was recently cloned and identified as transmembrane protein 97 (TMEM97), are neuroprotective. To determine structure–activity relationships for unexplored chemical space in our σ2R/Tmem97 ligand collection, we developed an in vivo high-content screening (HCS) assay to identify potential drug leads. The HCS assay uses our recently developed large-scale microfluidic immobilization chip and automated imaging platform. We discovered norbenzomorphans that reduced neurodegeneration in our <i>C. elegans</i> model, including two compounds that demonstrated significant neuroprotective activity at multiple doses. These findings provide further evidence that σ2R/Tmem97-binding norbenzomorphans may represent a new drug class for treating neurodegenerative diseases