| 1. |
- Ruilope, LM, et al.
(författare)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
|
|
| 2. |
- de Jong, R. S., et al.
(författare)
-
4MOST : Project overview and information for the First Call for Proposals
- 2019
-
Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
|
|
| 3. |
- Case, L. K., et al.
(författare)
-
Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking A beta fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for A beta afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection. The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking A beta fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.
|
|
| 4. |
|
|
| 5. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 6. |
- Betsou, F, et al.
(författare)
-
Standard PREanalytical Code Version 3.0
- 2018
-
Ingår i: Biopreservation and biobanking. - : Mary Ann Liebert Inc. - 1947-5543 .- 1947-5535. ; 16:1, s. 9-12
-
Tidskriftsartikel (refereegranskat)
|
|
| 7. |
- Case, L. K., et al.
(författare)
-
Ab-CT Affective Touch: Touch Pleasantness Ratings for Gentle Stroking and Deep Pressure Exhibit Dependence on A-Fibers
- 2023
-
Ingår i: Eneuro. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A prefer-ence for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway. Recently, ablation of the spinotha-lamic pathway-thought to convey all C-fiber sensations-in patients with cancer pain impaired pain, tempera-ture, and itch, but not ratings of pleasant touch. This suggested integration of afferent A and CT fiber input in the spinal cord, or mechanoreceptive A-fiber contributions to computations of touch pleasantness in the brain. However, contribution of mechanoreceptive A-fibers to touch pleasantness, in humans without pain, remains unknown. In the current, single-blinded study, we performed two types of peripheral nerve blocks in healthy adults to temporarily eliminate the contribution of A-fibers to touch perception. Our findings show that when mechanoreceptive A-fiber function is greatly diminished, the perceived intensity and pleasantness of both gen-tle stroking and deep pressure are nearly abolished. These findings demonstrate that explicit perception of the pleasantness of CT-targeted brushing and pressure both critically depend on afferent A-fibers.
|
|
| 8. |
- Repapi, Emmanouela, et al.
(författare)
-
Genome-wide association study identifies five loci associated with lung function.
- 2010
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:1, s. 36-44
-
Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
|
|
| 9. |
- Case, Laura K., et al.
(författare)
-
Encoding of Touch Intensity But Not Pleasantness in Human Primary Somatosensory Cortex
- 2016
-
Ingår i: Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 36:21, s. 5850-5860
-
Tidskriftsartikel (refereegranskat)abstract
- Growing interest in affective touch has delineated a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, have cast doubt on the segregation of touch discrimination and affect, suggesting that S1 also encodes affective qualities. We used functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to examine the role of S1 in processing touch intensity and pleasantness. Twenty-six healthy human adults rated brushing on the hand during fMRI. Intensity ratings significantly predicted activation in S1, whereas pleasantness ratings predicted activation only in the anterior cingulate cortex. Nineteen subjects also received inhibitory rTMS over right hemisphere S1 and the vertex (control). After S1 rTMS, but not after vertex rTMS, sensory discrimination was reduced and subjects with reduced sensory discrimination rated touch as more intense. In contrast, rTMS did not alter ratings of touch pleasantness. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1.
|
|
| 10. |
- Case, Laura K., et al.
(författare)
-
Inhibitory rTMS of secondary somatosensory cortex reduces intensity but not pleasantness of gentle touch
- 2017
-
Ingår i: Neuroscience Letters. - : ELSEVIER IRELAND LTD. - 0304-3940 .- 1872-7972. ; 653, s. 84-91
-
Tidskriftsartikel (refereegranskat)abstract
- Research suggests that the discriminative and affective aspects of touch are processed differently in the brain. Primary somatosensory cortex is strongly implicated in touch discrimination, whereas insular and prefronal regions have been associated with pleasantness aspects of touch. However, the role of secondary somatosensory cortex (S2) is less clear. In the current study we used inhibitory repetitive transcranial magnetic stimulation (rTMS) to temporarily deactivate S2 and probe its role in touch perception. Nineteen healthy adults received two sessions of 1-Hz rTMS on separate days, one targeting right S2 and the other targeting the vertex (control). Before and after rTMS, subjects rated the intensity and pleasantness of slow and fast gentle brushing of the hand and performed a 2-point tactile discrimination task, followed by fMRI during additional brushing. rTMS to S2 (but not vertex) decreased intensity ratings of fast brushing, without altering touch pleasantness or spatial discrimination. MRI showed a reduced response to brushing in S2 (but not in S1 or insula) after S2 rTMS. Together, our results show that reducing touch evoked activity in S2 decreases perceived touch intensity, suggesting a causal role of S2 in touch intensity perception. Published by Elsevier Ireland Ltd.
|
|
