The vanilloid receptor (VR1) is a ligand‐gated ion channel, which plays an important role in nociceptive processing. Therefore, a pharmacological characterization of the recently cloned rat VR1 ...(rVR1) was undertaken.
HEK293 cells stable expressing rVR1 (rVR1‐HEK293) were loaded with Fluo‐3AM and then incubated at 25°C for 30 min with or without various antagonists or signal transduction modifying agents. Then intracellular calcium concentrations (Ca2+i) were monitored using FLIPR, before and after the addition of various agonists.
The rank order of potency of agonists (resiniferatoxin (RTX)>capsaicin>olvanil>PPAHV) was as expected, and all were full agonists. The potencies of capsaicin and olvanil, but not RTX or PPAHV, were enhanced at pH 6.4 (pEC50 values of 7.47±0.06, 7.16±0.06, 8.19±0.06 and 6.02±0.03 respectively at pH 7.4 vs 7.71±0.05, 7.58±0.14, 8.10±0.05 and 6.04±0.08 at pH 6.4).
Capsazepine, isovelleral and ruthenium red all inhibited the capsaicin (100 nM)‐induced Ca2+ response in rVR1‐HEK293 cells, with pKB values of 7.52±0.08, 6.92±0.11 and 8.09±0.12 respectively (n=6 each). The response to RTX and olvanil were also inhibited by these compounds. None displayed any agonist‐like activity.
The removal of extracellular Ca2+ abolished, whilst inhibition of protein kinase C with chelerythrine chloride (10 μM) partially (∼20%) inhibited, the capsaicin (10 μM)‐induced Ca2+ response. However, tetrodotoxin (3 μM), nimodipine (10 μM), ω‐GVIA conotoxin (1 μM), thapsigargin (1 μM), U73122 (3 μM) or H‐89 (3 μM) had no effect on the capsaicin (100 nM)‐induced response.
In conclusion, the recombinant rVR1 stably expressed in HEK293 cells acts as a ligand‐gated Ca2+ channel with the appropriate agonist and antagonist pharmacology, and therefore is a suitable model for studying the effects of drugs at this receptor.
British Journal of Pharmacology (2000) 130, 916–922; doi:10.1038/sj.bjp.0703390
In today's increasingly competitive health care marketplace, consumer satisfaction has become an important measure of quality. Furthermore, measures of satisfaction with treatment inteerventions are ...influential factors in determining patients' and payers' choices of health care. This study sought to evaluate satisfaction with postmastectomy breast reconstruction and to assess the effects of procedure type and timing on patient satisfaction. As part of the Michigan Breast Reconstruction Outcome Study, patients undergoing first-time mastectomy reconstruction were prospectively evaluated, including cohorts of women choosing expander/implant, pedicle TRFAM flap, and free TRAM flap procedures. Preoperatively and 1 year postoperatively, participants completed a questionnaire that collected a variety of health status information. The postoperative questionnaire had an additional seven items assessing both general satisfaction with reconstruction (five items) and aesthetic satisfaction (two items) as separate subscales. Patients were asked to respond to each item using a five-point Likert scale. Item responses ranged from 1, indicating high satisfaction, to 5, reflecting low satisfaction. In the data analysis, only patients responding with a 1 or 2 for all of the items within a subscale were classified as "satisfied" for the subscale. To assess the effects of procedure type (implant, pedicle TRAM flap, and free TRAM flap) and timing (immediate versus delayed) on satisfaction and to control for possible confounding effects from other independent variables, multiple logistic regression was employed. In our analysis, odds ratios and associated 95 percent confidence intervals were calculated for each independent variable in the regression. Statistical significance was designated at the p < or = 0.05 level. A total of 212 patients were followed during the period of 1994 to 1997, including 141 immediate and 71 delayed reconstructions. The study population consisted of 49 expander/implant, 102 pedicle TRAM flap, and 61 free TRAM flap reconstruction patients. The analysis showed a significant association between procedure type and patient satisfaction. TRAM flap patients (both free and pedicle) appeared to have significantly greater general and aesthetic satisfaction compared with expander/implant patients (p = 0.03 and 0.001, respectively). Furthermore, pedicle TRAM flap patients were more aesthetically satisfied than those with free TRAM flaps (p = 0.072). The other independent variables of age and procedure timing did not appear to significantly affect either general or aesthetic satisfaction. However, preoperative physical activity was positively correlated with general satisfaction at the p = 0.034 level. The choice of procedure seems to have a significant effect on both aesthetic and general patient satisfaction with breast reconstruction. In this study, autogenous tissue reconstructions produced higher levels of patient aesthetic and general satisfaction compared with implant techniques. Pedicle and free TRAM flap patients do not seem to differ significantly in general satisfaction. However, women receiving pedicle TRAM flaps reported greater aesthetic satisfaction compared with patients undergoing free TRAM flaps. Furthermore, patient age and procedure timing may not have an effect on patient satisfaction with breast reconstruction.
In vitro data suggest that a subgroup of NLR proteins, including NLRP12, inhibits the transcription factor NF-κB, although physiologic and disease-relevant evidence is largely missing. Dysregulated ...NF-κB activity is associated with colonic inflammation and cancer, and we found Nlrp12−/− mice were highly susceptible to colitis and colitis-associated colon cancer. Polyps isolated from Nlrp12−/− mice showed elevated noncanonical NF-κB activation and increased expression of target genes that were associated with cancer, including Cxcl13 and Cxcl12. NLRP12 negatively regulated ERK and AKT signaling pathways in affected tumor tissues. Both hematopoietic- and nonhematopoietic-derived NLRP12 contributed to inflammation, but the latter dominantly contributed to tumorigenesis. The noncanonical NF-κB pathway was regulated upon degradation of TRAF3 and activation of NIK. NLRP12 interacted with both NIK and TRAF3, and Nlrp12−/− cells have constitutively elevated NIK, p100 processing to p52 and reduced TRAF3. Thus, NLRP12 is a checkpoint of noncanonical NF-κB, inflammation, and tumorigenesis.
► Nlrp12−/− mice are significantly more susceptible to colitis-associated colon cancer ► NLRP12 is a negative regulator NIK, CXCL12, CXCL13, ERK, and AKT in vivo ► Hematopoietic and nonhematopoietic compartments contribute to Nlrp12−/− phenotype ► NLRP12 functionally interacts with and alters the balance of NIK and TRAF3
We present a new reconstruction of the interplanetary magnetic field (IMF, B) for 1846–2012 with a full analysis of errors, based on the homogeneously constructed IDV(1d) composite of geomagnetic ...activity presented in Part 1 (Lockwood et al., 2013a). Analysis of the dependence of the commonly used geomagnetic indices on solar wind parameters is presented which helps explain why annual means of interdiurnal range data, such as the new composite, depend only on the IMF with only a very weak influence of the solar wind flow speed. The best results are obtained using a polynomial (rather than a linear) fit of the form B = χ · (IDV(1d) − β)α with best-fit coefficients χ = 3.469, β = 1.393 nT, and α = 0.420. The results are contrasted with the reconstruction of the IMF since 1835 by Svalgaard and Cliver (2010).
Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions ...that remain, a workshop was organized by IARC and the US NCI. A series of ‘difficult questions’ were formulated, which should be given future priority in the areas of population, genomic and clinical research.
The CUORE Cryostat D’Addabbo, A.; Alduino, C.; Bersani, A. ...
Journal of low temperature physics,
12/2018, Letnik:
193, Številka:
5-6
Journal Article
Recenzirano
Odprti dostop
The Cryogenic Underground Observatory for Rare Events (CUORE) is a bolometric experiment for neutrinoless double-beta decay in
130
Te
search, currently taking data at the underground facility of ...Laboratori Nazionali del Gran Sasso (LNGS). The CUORE cryostat successfully cooled down a mass of about 1 ton at
∼
7
mK
, delivering a uniform and constant base temperature. This result marks a fundamental milestone in low-temperature detector techniques, opening the path for future ton-scale bolometric experiments searching for rare events. In this paper, we present the CUORE cryogenic infrastructure, briefly describing its critical subsystems.
Abstract
Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB ...infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.
Meropenem-vaborbactam (MEV) is Food and Drug Administration-approved for selected Gram-negative bacterial (GNB) infections. We present the largest multi-center observational study to date describing early clinical experience with MEV in the treatment of GNB infections with clinical success of (70.0%).
Objective
The objective of this study was to identify criteria to be considered when developing an exoskeleton for low-back pain patients by exploring the perceptions and expectations of potential ...end users.
Background
Psychosocial, psychological, physical load, and personality influence incidence of low-back pain. Body-worn assistive devices that passively support the user’s trunk, that is exoskeletons, can decrease mechanical loading and potentially reduce low-back pain. A user-centered approach improves patient safety and health outcomes, increases user satisfaction, and ensures usability. Still, previous studies have not taken psychological factors and the early involvement of end users into account.
Method
We conducted focus group studies with low-back pain patients (n = 4) and health care professionals (n = 8). Focus group sessions were audio-recorded, transcribed, and analyzed, using the general inductive approach. The focus group discussions included trying out an available exoskeleton. Questions were designed to elicit opinions about exoskeletons, desired design specifications, and usability.
Results
Important design characteristics were comfort, individual adjustability, independency in taking it on and off, and gradual adjustment of support. Patients raised concerns over loss of muscle strength. Health care professionals mentioned the risk of confirming disability of the user and increasing guarded movement in patients.
Conclusion
The focus groups showed that implementation of a trunk exoskeleton to reduce low-back pain requires an adequate implementation strategy, including supervision and behavioral coaching.
Application
For health care professionals, the optimal field of application, prevention or rehabilitation, is still under debate. Patients see potential in an exoskeleton to overcome their limitations and expect it to improve their quality of life.
The Earth‐directed coronal mass ejection (CME) of 8 April 2010 provided an opportunity for space weather predictions from both established and developmental techniques to be made from near–real time ...data received from the SOHO and STEREO spacecraft; the STEREO spacecraft provide a unique view of Earth‐directed events from outside the Sun‐Earth line. Although the near–real time data transmitted by the STEREO Space Weather Beacon are significantly poorer in quality than the subsequently downlinked science data, the use of these data has the advantage that near–real time analysis is possible, allowing actual forecasts to be made. The fact that such forecasts cannot be biased by any prior knowledge of the actual arrival time at Earth provides an opportunity for an unbiased comparison between several established and developmental forecasting techniques. We conclude that for forecasts based on the STEREO coronagraph data, it is important to take account of the subsequent acceleration/deceleration of each CME through interaction with the solar wind, while predictions based on measurements of CMEs made by the STEREO Heliospheric Imagers would benefit from higher temporal and spatial resolution. Space weather forecasting tools must work with near–real time data; such data, when provided by science missions, is usually highly compressed and/or reduced in temporal/spatial resolution and may also have significant gaps in coverage, making such forecasts more challenging.
Ocean deoxygenation threatens ocean productivity, carbon cycling and marine ecosystems. Shelf seas are highly dynamic regions, which contributes to their high productivity and also makes monitoring ...and constraining their oxygen status a challenge. Here, using the temperate Celtic shelf sea (April and July 2015) as a case study, we present high‐resolution ocean glider observations of turbulence and biogeochemical parameters, demonstrating the potential of these autonomous platforms for environmental monitoring. We estimate vertical turbulent oxygen fluxes be 25% higher in summer than in spring, due to the presence of subsurface chlorophyll and associated oxygen maxima at the seasonal thermocline. We demonstrate that glider‐based estimates were able to constrain similar bottom layer respiration rates as those derived from traditional ship‐based measurements. We suggest ocean gliders are useful monitoring tools that can aid sustainable management of shelf sea ecosystems.
Plain Language Summary
Oxygen levels in the ocean are decreasing. Oxygen is needed by almost all life in the oceans, thus low oxygen levels can result in dramatic changes to marine ecosystems. The decrease in oxygen levels is particularly alarming in the coastal ocean or “shelf sea” (the region between the land and the deep open ocean), which supports the majority of global fisheries (over 90%). Therefore, there is both an urgent societal and an environmental need to better understand processes influencing oxygen levels in the coastal ocean, such as physical water circulation and mixing, and biological oxygen production and consumption. Here we present turbulent mixing data collected over 40 days in a typical shelf sea using an unmanned, autonomous underwater vehicle (AUV) called an ocean glider. We use this data combined with oxygen data to calculate the contribution of physical oxygen fluxes to the observed change in oxygen, and from this deduce how much of the change was driven by biology. We prove that AUVs may be used as an effective method for monitoring oxygen dynamics and that this can aid responsible marine management in shelf seas.
Key Points
Glider observations are able to integrate physical and biogeochemical processes influencing oxygen depletion in shelf seas
Mixing and advection replenish respired oxygen in the bottom mixed layer
The presence of a subsurface oxygen maxima results in larger oxygen fluxes to the bottom mixed layer in summer compared to spring
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