We report the discovery of HATS-71b, a transiting gas giant planet on a day orbit around a mag M3 dwarf star. HATS-71 is the coolest M dwarf star known to host a hot Jupiter. The loss of light during ...transits is 4.7%, more than in any other confirmed transiting planet system. The planet was identified as a candidate by the ground-based HATSouth transit survey. It was confirmed using ground-based photometry, spectroscopy, and imaging, as well as space-based photometry from the NASA Transiting Exoplanet Survey Satellite mission (TIC 234523599). Combining all of these data, and utilizing Gaia DR2, we find that the planet has a radius of and mass of (95% confidence upper limit of ), while the star has a mass of and a radius of .
The gut‐born incretin hormone glucagon‐like peptide‐1 (GLP‐1) delays gastric emptying. To elucidate the mechanisms by which GLP‐1 affects gastroduodenal motility and glycaemia, we studied the effects ...of exendin(9–39), a potent GLP‐1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double‐blind, placebo‐controlled, four‐arm, cross‐over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9–39), atropine, exendin(9–39) + atropine or saline were infused intravenously. Antro‐pyloro‐duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9–39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9–39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9–39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9–39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9–39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP‐1 secretion. Cholinergic mechanisms mediate the effects of GLP‐1 on postprandial gastric accommodation but not on antro‐pyloro‐duodenal motility. GLP‐1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.
Summary
Background Recent studies suggest a role for the endocannabinoid system, including fatty acid amide hydrolase (FAAH), in intestinal inflammation.
Aim To analyse FAAH expression and the FAAH ...385 C/A (p.Pro129Thr; rs324420) single nucleotide polymorphism (SNP) in‐patients with Crohn’s disease (CD) and ulcerative colitis (UC).
Patients and methods Genomic DNA from 1008 individuals (CD: n = 435; UC: n = 167; controls: n = 406) was analysed for the FAAH 385 C/A SNP. We determined FAAH mRNA expression by quantitative PCR in CD and UC lesions as well as in intestinal epithelial cells (IECs).
Results There were no significant differences regarding the frequency of this SNP in the three study groups (CD, UC, controls). However, CD patients homozygous for the FAAH p.Pro129Thr polymorphism were more likely to develop a severe disease phenotype associated with fistulas (P = 0.03, OR 3.12, 95% CI 1.08–8.98) and extra‐intestinal manifestations (P = 0.005, OR 4.29, CI 1.49–12.35). In UC, homozygous carriers had an earlier disease onset than wild‐type carriers (P = 0.01). FAAH mRNA expression correlated with IL‐8 mRNA expression in CD lesions (r = 0.53). However, pro‐inflammatory stimuli did not significantly increase FAAH mRNA expression in IECs.
Conclusion The FAAH p.Pro129Thr polymorphism may modulate the CD phenotype.
Summary
Background Serum C‐reactive protein (CRP) levels influence the response to anti‐tumour necrosis factor (TNF) therapies.
Aim To analyse the influence of the +1059G/C CRP polymorphism on CRP ...serum levels and disease susceptibility in patients with Crohn's disease (CD).
Methods Using restriction fragment length polymorphism (RFLP) analysis, genomic DNA from 241 CD patients and 199 unrelated controls was analysed for the +1059G/C substitution in the CRP gene and the common caspase‐activation recruitment domain 15 (CARD15) variants.
Results Homozygous C/C carriers were detected only among CD patients (P = 0.066). Patients with ileal involvement (L1 and L3 phenotype) were found in only 58.4% of patients with the wildtype G/G genotype but in 88.2% of the heterozygous G/C carriers (OR 5.26; 95% CI 1.19–23.92) and four of the five C/C homozygous carriers (80%; OR 4.55; 95% CI 1.64–16.67; P = 0.008 for hetero‐ and homozygous carriers vs. wildtype) which was independent of the presence of CARD15 variants. Increased CD activity was associated with increased CRP serum levels (P < 0.005). For Crohn's disease activity index (CDAI) < 150, C/C homozygosity for the +1059 G/C polymorphism was associated with significantly lower CRP serum levels (P < 0.01).
Conclusions The C allele of the CRP +1059G/C polymorphism is associated with decreased serum CRP levels and increased likelihood of disease involvement of the terminal ileum in CD patients.
This prospective trial was designed to compare the performance characteristics of five different screening tests in parallel for the detection of advanced colonic neoplasia: CT colonography (CTC), ...colonoscopy (OC), flexible sigmoidoscopy (FS), faecal immunochemical stool testing (FIT) and faecal occult blood testing (FOBT).
Average risk adults provided stool specimens for FOBT and FIT, and underwent same-day low-dose 64-multidetector row CTC and OC using segmentally unblinded OC as the standard of reference. Sensitivities and specificities were calculated for each single test, and for combinations of FS and stool tests. CTC radiation exposure was measured, and patient comfort levels and preferences were assessed by questionnaire.
221 adenomas were detected in 307 subjects who completed CTC (mean radiation dose, 4.5 mSv) and OC; 269 patients provided stool samples for both FOBT and FIT. Sensitivities of OC, CTC, FS, FIT and FOBT for advanced colonic neoplasia were 100% (95% CI 88.4% to 100%), 96.7% (82.8% to 99.9%), 83.3% (95% CI 65.3% to 94.4%), 32% (95% CI 14.9% to 53.5) and 20% (95% CI 6.8% to 40.7%), respectively. Combination of FS with FOBT or FIT led to no relevant increase in sensitivity. 12 of 45 advanced adenomas were smaller than 10 mm. 46% of patients preferred CTC and 37% preferred OC (p<0.001).
High-resolution and low-dose CTC is feasible for colorectal cancer screening and reaches sensitivities comparable with OC for polyps >5 mm. For patients who refuse full bowel preparation and OC or CTC, FS should be preferred over stool tests. However, in cases where stool tests are performed, FIT should be recommended rather than FOBT.
The GAPS programme at TNG Montalto, M.; Greco, N.; Biazzo, K. ...
Astronomy and astrophysics (Berlin),
07/2024, Letnik:
687
Journal Article
Recenzirano
Aims . We report the confirmation of a new transiting exoplanet orbiting the star TOI-5076. Methods . We present our vetting procedure and follow-up observations which led to the confirmation of the ...exoplanet TOI-5076b. In particular, we employed high-precision TESS photometry, high-angular-resolution imaging from several telescopes, and high-precision radial velocities from HARPS-N. Results . From the HARPS-N spectroscopy, we determined the spectroscopic parameters of the host star: T eff = (5070±143) K, log = (4.6±0.3), Fe/H = (+0.20±0.08), and α /Fe = 0.05±0.06. The transiting planet is a warm sub-Neptune with a mass m p = (16±2) M ⊙ , a radius r p =(3.2±0.l) R ⊙ yielding a density ρ p = (2.8±0.5) g cm −3 . It revolves around its star approximately every 23.445 days. Conclusions . The host star is a metal-rich, K2V dwarf, located at about 82 pc from the Sun with a radius of R ⋆ = (0.78±0.01) R ⊙ and a mass of M ⋆ = (0.80±0.07) M ⊙ . It forms a common proper motion pair with an M-dwarf companion star located at a projected separation of 2178 au. The chemical analysis of the host-star and the Galactic-space velocities indicate that TOI-5076 belongs to the old population of thin-to-thick-disk transition stars. The density of TOI-5076b suggests the presence of a large fraction by volume of volatiles overlying a massive core. We found that a circular orbit solution is marginally favored with respect to an eccentric orbit solution for TOI-5076b.
The GAPS programme at TNG Montalto, M; Greco, N; Biazzo, K ...
Astronomy and astrophysics (Berlin),
07/2024, Letnik:
687
Journal Article
Recenzirano
Aims. We report the confirmation of a new transiting exoplanet orbiting the star TOI-5076. Methods. We present our vetting procedure and follow-up observations which led to the confirmation of the ...exoplanet TOI-5076b. In particular, we employed high-precision TESS photometry, high-angular-resolution imaging from several telescopes, and high-precision radial velocities from HARPS-N. Results. From the HARPS-N spectroscopy, we determined the spectroscopic parameters of the host star: Teff = (5070±143) K, log ?? = (4.6±0.3), Fe/H = (+0.20±0.08), and α/Fe = 0.05±0.06. The transiting planet is a warm sub-Neptune with a mass mp = (16±2) M⊙, a radius rp =(3.2±0.l) R⊙ yielding a density ρp = (2.8±0.5) g cm−3. It revolves around its star approximately every 23.445 days. Conclusions. The host star is a metal-rich, K2V dwarf, located at about 82 pc from the Sun with a radius of R⋆ = (0.78±0.01) R⊙ and a mass of M⋆ = (0.80±0.07) M⊙. It forms a common proper motion pair with an M-dwarf companion star located at a projected separation of 2178 au. The chemical analysis of the host-star and the Galactic-space velocities indicate that TOI-5076 belongs to the old population of thin-to-thick-disk transition stars. The density of TOI-5076b suggests the presence of a large fraction by volume of volatiles overlying a massive core. We found that a circular orbit solution is marginally favored with respect to an eccentric orbit solution for TOI-5076b.
Interleukin 26 (IL-26), a novel IL-10-like cytokine without a murine homologue, is expressed in T helper 1 (Th1) and Th17 cells. Currently, its function in human disease is completely unknown. The ...aim of this study was to analyse its role in intestinal inflammation.
Expression studies were performed by reverse transcription-PCR (RT-PCR), quantitative PCR, western blot and immunohistochemistry. Signal transduction was analysed by western blot experiments and ELISA. Cell proliferation was measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. IL-26 serum levels were determined by an immunoluminometric assay (ILMA).
All examined intestinal epithelial cell (IEC) lines express both IL-26 receptor subunits IL-20R1 and IL-10R2. IL-26 activates extracellular signal-related kinase (ERK)-1/2 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein (MAP) kinases, Akt and signal transducers and activators of transcription (STAT) 1/3. IL-26 stimulation increases the mRNA expression of proinflammatory cytokines but decreases cell proliferation. In inflamed colonic lesions of patients with Crohn's disease, an elevated IL-26 mRNA expression was found that correlated highly with the IL-8 and IL-22 expression. Immunohistochemical analysis demonstrated IL-26 protein expression in colonic T cells including Th17 cells expressing the orphan nuclear receptor RORgammat, with an increased number of colonic IL-26-expressing cells in active Crohn's disease.
Intestinal cells express the functional IL-26 receptor complex. IL-26 modulates IEC proliferation and proinflammatory gene expression and its expression is upregulated in active Crohn's disease, indicating a role for this cytokine system in the innate host cell response during intestinal inflammation. For the first time, IL-26 expression is demonstrated in colonic RORgammat-expressing Th17 cells in situ, supporting a role for this cell type in the pathogenesis of Crohn's disease.
Glucagon-like peptide-1-(7–36)-amide (GLP-1) is involved in satiety control and glucose homeostasis. Animal studies suggest a physiological role for GLP-1 in water and salt homeostasis. This study’s ...aim was to define the effects of GLP-1 on water and sodium excretion in both healthy and obese men.
Fifteen healthy subjects and 16 obese men (mean body mass index, 36 kg/m2) were examined in a double-blind, placebo-controlled, crossover study to demonstrate the effects of a 3-h infusion of GLP-1 on urinary sodium excretion, urinary output, and the glomerular filtration rate after an iv 9.9-g salt load.
Infusion of GLP-1 evoked a dose-dependent increase in urinary sodium excretion in healthy subjects (from 74 ± 8 to 143 ± 18 mmol/180 min, P = 0.0013). In obese men, there was a significant increase in urinary sodium excretion (from 59 to 96 mmol/180 min, P = 0.015), a decrease in urinary H+ secretion (from 1.1 to 0.3 pmol/180 min, P = 0.013), and a 6% decrease in the glomerular filtration rate (from 151 ± 8 to 142 ± 8 ml/min, P = 0.022).
Intravenous infusions of GLP-1 enhance sodium excretion, reduce H+ secretion, and reduce glomerular hyperfiltration in obese men. These findings suggest an action at the proximal renal tubule and a potential renoprotective effect.
Context:
The phosphodiesterase 4 inhibitor roflumilast is a first-in-class antiinflammatory treatment for severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis and a ...history of frequent exacerbations. In previous clinical studies, a transient and reversible weight decrease was reported with roflumilast, suggesting the systemic actions of this drug may impact metabolism.
Objective:
Our objective was to investigate the effects of roflumilast on glucose homeostasis and body weight.
Design and Setting:
We conducted a 12-wk, randomized, double-blind, placebo-controlled multicenter study with outpatients.
Patients:
Patients (n = 205) with newly diagnosed type 2 diabetes mellitus (DM2) but without COPD were included in the study.
Interventions:
Roflumilast 500 μg or placebo was administered once daily.
Primary Outcome:
We evaluated mean change in blood glycated hemoglobin levels.
Secondary Outcomes:
We also evaluated mean change from baseline in the postmeal area under the curve (AUC) for a range of metabolic parameters.
Results:
Roflumilast was associated with a significantly greater reduction in glycated hemoglobin levels than placebo (least square mean = −0.45%; P < 0.0001) in patients with DM2. In the roflumilast group, postmeal AUC decreased significantly from baseline to last visit for free fatty acids, glycerol, glucose, and glucagon, whereas they slightly increased for C-peptide and insulin. In contrast to roflumilast, the glucagon AUC increased with placebo, and the insulin AUC decreased. Between-treatment analysis revealed statistically significant differences in favor of roflumilast for glucose (P = 0.0082), glycerol (P = 0.0104), and C-peptide levels (P = 0.0033). Patients in both treatment groups lost weight, although the between-treatment difference of the changes from baseline to last visit −0.7 (0.4) kg was not statistically significant (P = 0.0584).
Conclusion:
Roflumilast lowered glucose levels in patients with newly diagnosed DM2 without COPD, suggesting positive effects on glucose homoeostasis.
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