Optical Methods for Imaging Ionic Activities

Optical fluorescence is characteristic of molecules and their environment, and dyes can be made whose fluorescence is altered by reversible binding to specific ions. By introducing these into the cytosol, fluorescence microscopy can be used to form dynamic images of ionic activities in living cells under experimental manipulation. Optical fluorescence spectra are broad-band, and if specific ion binding alters the wavelength of maximal excitation or emission, quantitative measurements can be made from the ratio of images taken at two different wavelengths, eliminating errors due to spatial variations in dye concentration and optical path-length. This method is analogous to continuum normalisation in X-ray microanalysis, and is implemented using a sensitive video camera and computer processing of digitised images. Fluorescent indicators exist for calcium, magnesium, hydrogen, sodium, zinc and chloride ions. Most imaging work has been on calcium, which is important in many cell signalling processes, and several calcium indicators are available with different spectral properties. Spatial resolution is limited to a few μm by out-of-focus blur, but repeated images can be captured with a time resolution as low as 200 msec, and by using dyes with high binding affinity, detection limits can be lower than by X-ray methods. There is a large and fast-growing literature of applications to many plant and animal cell-types

Aphelenchoides sp. destroying mushroom mycelium

RESP-357

Reliability and responsiveness of measures of pain in people with osteoarthritis of the knee: a psychometric evaluation

PURPOSE: To examine the fit between data from the Short Form McGill Pain Questionnaire (SF-MPQ-2) and the Rasch model, and to explore the reliability and internal responsiveness of measures of pain in people with knee osteoarthritis. METHODS: Participants with knee osteoarthritis completed the SF-MPQ-2, Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP) and painDETECT. Participants were sent the same questionnaires 3 and 6 months later. RESULTS: Fit to the Rasch model was not achieved for the SF-MPQ-2 Total scale. The Continuous subscale yielded adequate fit statistics after splitting item 10 on uniform DIF for gender, and removing item 9. The Intermittent subscale fit the Rasch model after rescoring items. The Neuropathic subscale had relatively good fit to the model. Test-retest reliability was satisfactory for most scales using both original and Rasch scoring ranging from fair to substantial. Effect sizes ranged from 0.13 to 1.79 indicating good internal responsiveness for most scales. CONCLUSIONS: These findings support the use of ICOAP subscales as reliable and responsive measure of pain in people with knee osteoarthritis. The MPQ-SF-2 subscales found to be acceptable alternatives. Implications for Rehabilitation The McGill Pain Questionnaire short version 2 is not a unidimensional scale in people with knee osteoarthritis, whereas three of the subscales are unidimensional. The McGill Pain Questionnaire short version 2 Affective subscale does not have good measurement properties for people with knee osteoarthritis. The McGill Pain Questionnaire short version 2 and the Intermittent and Constant Osteoarthritis Pain scales can be used to assess change over time. The painDETECT performs better as a screening measure than as an outcome measure

Evaluation of a group acceptance commitment therapy intervention for people with knee or hip osteoarthritis: a pilot randomized controlled trial

Objectives: The aim was to evaluate an Acceptance Commitment Therapy (ACT) intervention for people with knee or hip osteoarthritis; a related aim was to compare treatment effects from Rasch-transformed and standard scales. Methods: Participants were recruited from a research database and outpatient rheumatology and orthopaedic clinics at two hospitals. Eligible participants were randomly allocated to either intervention or usual care. Intervention comprised six-sessions of group ACT. Outcomes were assessed two and four months after randomisation. Rasch-transformed and standard self-report measures were compared. Qualitative interviews also explored the acceptability of the intervention. Results: Of 8 people assessed for eligibility, 31 (36%) were randomised. The main reason for non-randomisation was that participants received surgery. Of the 16 participants randomised to intervention, 64% completed ≥50% of the scheduled group sessions. Follow-up data was complete for 84% participants at two months and 68% at four months. Outcome analysis demonstrated important differences between the Rasch-transformed and standard scales. There were significant differences between the groups in pain. Qualitative interviews with 7 participants suggested the intervention was acceptable. Conclusions: ACT for osteoarthritis is likely to be an acceptable treatment option for people with osteoarthritis. Progress to a definitive trial is warranted. Rasch-transformed outcome scales are preferable in clinical trials where possible

Impact of early exposure to a cafeteria diet on prefrontal cortex monoamines and novel object recognition in adolescent rats

© 2019 Elsevier B.V. The prefrontal cortex (PFC) undergoes protracted postnatal development such that its structure and behavioural function may be profoundly altered by environmental factors. Here we investigate the effect of lactational dietary manipulations on novel object recognition (NOR) learning and PFC monoamine neurotransmitter metabolism in early adolescent rats. To this end, Wistar rat dams were fed a high caloric cafeteria diet (CD) during lactation and resultant 24–26 day old offspring exposed to NOR testing and simultaneous PFC dopamine and serotonin metabolism measurement. In the second NOR choice trial where one familiar and one novel object were presented controls explored the novel preferentially to the familiar object both after a 5 min (P < 0.001) or 30 min (P < 0.05) inter-trial intervals (ITI). By contrast, offspring from dams fed on lactational CD failed to show any significant preference for the novel object at either time point. Compared with chow fed controls, their average exploration ratio of the novel object was lower after the 5 min ITI (P < 0.05). Following a 60 min ITI, neither CD nor control offspring showed a preference for the novel object. PFC dopamine metabolism was significantly reduced in the CD group (P < 0.001), whereas serotonin metabolism was increased (P < 0.001). These results suggest that an obesogenic lactational diet can have a detrimental impact on cognition in adolescent offspring associated with aberrant PFC serotonin and dopamine metabolism

Coronal Shock Waves, EUV waves, and their Relation to CMEs. II. Modeling MHD Shock Wave Propagation Along the Solar Surface, Using Nonlinear Geometrical Acoustics

We model the propagation of a coronal shock wave, using nonlinear geometrical acoustics. The method is based on the Wentzel-Kramers-Brillouin (WKB) approach and takes into account the main properties of nonlinear waves: i) dependence of the wave front velocity on the wave amplitude, ii) nonlinear dissipation of the wave energy, and iii) progressive increase in the duration of solitary shock waves. We address the method in detail and present results of the modeling of the propagation of shock-associated extreme-ultraviolet (EUV) waves as well as Moreton waves along the solar surface in the simplest solar corona model. The calculations reveal deceleration and lengthening of the waves. In contrast, waves considered in the linear approximation keep their length unchanged and slightly accelerate.Comment: 15 pages, 7 figures, accepted for publication in Solar Physic

Personal experience of osteoarthritis and pain questionnaires: mapping items to themes

Purpose. The aim of this study was to examine the correspondence between qualitative and quantitative methods of coding experience of pain reported by participants with osteoarthritis (OA) of the knee. Method. A mapping grid was produced to record the correspondence between subthemes that emerged from thematic analysis of interviews with 24 participants with knee OA, and from questionnaire items which were used in a study of 192 knee OA participants. Items were rated according to their degree of correspondence between subthemes and questionnaire items and an overall correspondence score was produced for each subtheme and questionnaire measure. Results. The subthemes that corresponded well with the questionnaire items were those that related to socio-emotional functioning, the overall experience of pain and the impact of pain on physical functioning. The questionnaire items did not relate to participants' knowledge about their condition and their experience of the medical system. Conclusions. The study indicated that many aspects of pain experience reported by patients in qualitative interviews are also assessed by commonly used questionnaire outcome measures for people with pain. However, although participants reported that knowledge about their condition and their experience of the medical system were important aspects of the overall pain experience, these are rarely used as outcome measures. Questionnaires that address these additional aspects ofthe pain experience could be useful to further evaluate the experience of pain and may help to address importance concerns raised by patients with OA of the knee

Factors determining uptake of diabetic retinopathy screening in Oxfordshire

AIMS: To investigate variables at the demographic and primary care practice levels that influence the uptake of diabetic retinopathy screening. METHODS: Data were extracted from the management software of one screening programme for 21 797 people registered with 79 general practices. Uptake was examined by gender, age group, modality of screening (mobile unit at general practice versus high-street optometrist), and by general practice. A telephone survey of high-street optometrists provided information on the availability of screening appointments. RESULTS: Uptake was 82.4% during the study period, and was higher for men (83.2%) than for women (81.5%) (P = 0.001). Uptake varied by age group (P < 0.001), being lowest in those aged 12-39 years (67%). Uptake was higher for people invited to a general practice for screening by a mobile unit (83.5%) than for those invited for screening by a high-street optometrist (82%) (P = 0.006). After adjusting for these factors and for socio-economic deprivation score at the location of the general practice, heterogeneity in uptake rate was still observed between some practices. Our survey of optometrists indicated wide variation in the availability of time slots for screening during the week and of screening appointment provision. CONCLUSIONS: Diabetic retinopathy screening services do not achieve high uptake among the youngest or oldest age groups. Practices in the least deprived areas had the highest uptake. Variation in uptake between general practices after adjustment for individual-level variables and deprivation suggests that practice-level factors may have an important role in determining rates of screening attendance

ER stress and Rho kinase activation underlie the vasculopathy of CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) leads to premature stroke and vascular dementia. Mechanism-specific therapies for this aggressive cerebral small vessel disease are lacking. CADASIL is caused by NOTCH3 mutations that influence vascular smooth muscle cell (VSMC) function through unknown processes. We investigated molecular mechanisms underlying the vasculopathy in CADASIL focusing on endoplasmic reticulum (ER) stress and RhoA/Rho kinase (ROCK). Peripheral small arteries and VSMCs were isolated from gluteal biopsies of CADASIL patients and mesentery of TgNotch3R169C mice (CADASIL model). CADASIL vessels exhibited impaired vasorelaxation, blunted vasoconstriction, and hypertrophic remodeling. Expression of NOTCH3 and ER stress target genes was amplified and ER stress response, Rho kinase activity, superoxide production, and cytoskeleton-associated protein phosphorylation were increased in CADASIL, processes associated with Nox5 upregulation. Aberrant vascular responses and signaling in CADASIL were ameliorated by inhibitors of Notch3 (γ-secretase inhibitor), Nox5 (mellitin), ER stress (4-phenylbutyric acid), and ROCK (fasudil). Observations in human CADASIL were recapitulated in TgNotch3R169C mice. These findings indicate that vascular dysfunction in CADASIL involves ER stress/ROCK interplay driven by Notch3-induced Nox5 activation and that NOTCH3 mutation–associated vascular pathology, typical in cerebral vessels, also manifests peripherally. We define Notch3-Nox5/ER stress/ROCK signaling as a putative mechanism-specific target and suggest that peripheral artery responses may be an accessible biomarker in CADASIL