Differential effects of RYGB surgery and best medical treatment for obesity-diabetes on intestinal and islet adaptations in obese-diabetic ZDSD rats

Modification of gut-islet secretions after Roux-En-Y gastric bypass (RYBG) surgery contributes to its metabolic and anti-diabetic benefits. However, there is limited knowledge on tissue-specific hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were excised from male Zucker-Diabetic Sprague Dawley (ZDSD) rats 8-weeks after RYGB, BMT (daily oral dosing with metformin 300mg/kg, fenofibrate 100mg/kg, ramipril 1mg/kg, rosuvastatin 10mg/kg and subcutaneous liraglutide 0.2mg/kg) or sham operation (laparotomy). Insulin, glucagon, somatostatin, PYY, GLP-1 and GIP expression patterns were assessed using immunocytochemistry and analyzed using ImageJ. After RYGB and BMT, body weight and plasma glucose were decreased. Intestinal morphometry was unaltered by RYGB, but crypt depth was decreased by BMT. Intestinal PYY cells were increased by both interventions. GLP-1- and GIP-cell counts were unchanged by RYGB but BMT increased ileal GLP-1-cells and decreased those expressing GIP. The intestinal contents of PYY and GLP-1 were significantly enhanced by RYGB, whereas BMT decreased ileal GLP-1. No changes of islet and beta-cell area or proliferation were observed, but the extent of beta-cell apoptosis and islet integrity calculated using circularity index were improved by both treatments. Significantly decreased islet alpha-cell areas were observed in both groups, while beta- and PYY-cell areas were unchanged. RYGB also induced a decrease in islet delta-cell area. PYY and GLP-1 colocalization with glucagon in islets was significantly decreased in both groups, while co-staining of PYY with glucagon was decreased and that with somatostatin increased. These data characterize significant cellular islet and intestinal adaptations following RYGB and BMT associated with amelioration of obesity-diabetes in ZDSD rats. The differential responses observed and particularly those within islets, may provide important clues to the unique ability of RYGB to cause diabetes remission

Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis.

Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women

Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis

Background: Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. Methods: All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. Results: Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. Conclusion: This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women

Kepler-20: A Sun-like Star with Three Sub-Neptune Exoplanets and Two Earth-size Candidates

We present the discovery of the Kepler-20 planetary system, which we initially identified through the detection of five distinct periodic transit signals in the Kepler light curve of the host star 2MASSJ19104752+4220194. We find a stellar effective temperature Teff=5455+-100K, a metallicity of [Fe/H]=0.01+-0.04, and a surface gravity of log(g)=4.4+-0.1. Combined with an estimate of the stellar density from the transit light curves we deduce a stellar mass of Mstar=0.912+-0.034 Msun and a stellar radius of Rstar=0.944^{+0.060}_{-0.095} Rsun. For three of the transit signals, our results strongly disfavor the possibility that these result from astrophysical false positives. We conclude that the planetary scenario is more likely than that of an astrophysical false positive by a factor of 2e5 (Kepler-20b), 1e5 (Kepler-20c), and 1.1e3 (Kepler-20d), sufficient to validate these objects as planetary companions. For Kepler-20c and Kepler-20d, the blend scenario is independently disfavored by the achromaticity of the transit: From Spitzer data gathered at 4.5um, we infer a ratio of the planetary to stellar radii of 0.075+-0.015 (Kepler-20c) and 0.065+-0.011 (Kepler-20d), consistent with each of the depths measured in the Kepler optical bandpass. We determine the orbital periods and physical radii of the three confirmed planets to be 3.70d and 1.91^{+0.12}_{-0.21} Rearth for Kepler-20b, 10.85 d and 3.07^{+0.20}_{-0.31} Rearth for Kepelr-20c, and 77.61 d and 2.75^{+0.17}_{-0.30} Rearth for Kepler-20d. From multi-epoch radial velocities, we determine the masses of Kepler-20b and Kepler-20c to be 8.7\+-2.2 Mearth and 16.1+-3.5 Mearth, respectively, and we place an upper limit on the mass of Kepler-20d of 20.1 Mearth (2 sigma).Comment: accepted by ApJ, 58 pages, 12 figures revised Jan 2012 to correct table 2 and clarify planet parameter extractio

K2 discovers a busy bee: an unusual transiting Neptune found in the beehive cluster

Open clusters have been the focus of several exoplanet surveys, but only a few planets have so far been discovered. The Kepler spacecraft revealed an abundance of small planets around small cool stars, therefore, such cluster members are prime targets for exoplanet transit searches. Kepler's new mission, K2, is targeting several open clusters and star-forming regions around the ecliptic to search for transiting planets around their low-mass constituents. Here, we report the discovery of the first transiting planet in the intermediate-age (800 Myr) Beehive cluster (Praesepe). K2-95 is a faint (Kp = 15.5 mag) dwarf from K2's Campaign 5 with an effective temperature of 3471 ±124 K, approximately solar metallicity and a radius of 0.402± 0.050.R⊕ We detected a transiting planet with a radius of3.47+0.78 -0.53R⊕ and an orbital period of 10.134 days. We combined photometry, medium/high-resolution spectroscopy, adaptive optics/speckle imaging, and archival survey images to rule out any false-positive detection scenarios, validate the planet, and further characterize the system. The planet's radius is very unusual as M-dwarf field stars rarely have Neptune-sized transiting planets. The comparatively large radius of K2-95b is consistent with the other recently discovered cluster planets K2-25b (Hyades) and K2-33b (Upper Scorpius), indicating systematic differences in their evolutionary states or formation. These discoveries from K2 provide a snapshot of planet formation and evolution in cluster environments and thus make excellent laboratories to test differences between field-star and cluster planet populations

Kepler-21b: A 1.6REarth Planet Transiting the Bright Oscillating F Subgiant Star HD 179070

We present Kepler observations of the bright (V=8.3), oscillating star HD 179070. The observations show transit-like events which reveal that the star is orbited every 2.8 days by a small, 1.6 R_Earth object. Seismic studies of HD 179070 using short cadence Kepler observations show that HD 179070 has a frequencypower spectrum consistent with solar-like oscillations that are acoustic p-modes. Asteroseismic analysis provides robust values for the mass and radius of HD 179070, 1.34{\pm}0.06 M{\circ} and 1.86{\pm}0.04 R{\circ} respectively, as well as yielding an age of 2.84{\pm}0.34 Gyr for this F5 subgiant. Together with ground-based follow-up observations, analysis of the Kepler light curves and image data, and blend scenario models, we conservatively show at the >99.7% confidence level (3{\sigma}) that the transit event is caused by a 1.64{\pm}0.04 R_Earth exoplanet in a 2.785755{\pm}0.000032 day orbit. The exoplanet is only 0.04 AU away from the star and our spectroscopic observations provide an upper limit to its mass of ~10 M_Earth (2-{\sigma}). HD 179070 is the brightest exoplanet host star yet discovered by Kepler.Comment: Accepted to Ap

Recurrence and Survival after Minimally Invasive and Open Esophagectomy for Esophageal Cancer: A Post Hoc Analysis of the Ensure Study

Objective: To determine the impact of operative approach [open (OE), hybrid minimally invasive (HMIE), and total minimally invasive (TMIE) esophagectomy] on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer. Background: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear. Methods: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009 and 2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield, and overall survival (OS). Results: In total, 3199 patients were included. Of these, 55% underwent OE, 17% HMIE, and 29% TMIE. DFS was independently increased post-TMIE [hazard ratio (HR): 0.86 (95% CI: 0.76-0.98), P = 0.022] compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to the operative approach [HMIE vs OE, odds ratio (OR): 0.79, P = 0.257; TMIE vs OE, OR: 0.84, P = 0.243]. The probability of systemic recurrence was independently increased post-HMIE (OR: 2.07, P = 0.031), but not TMIE (OR: 0.86, P = 0.508). R0 resection rates (P = 0.005) and nodal yield (P < 0.001) were independently increased after TMIE, but not HMIE (P = 0.424; P = 0.512) compared with OE. OS was independently improved following both HMIE (HR: 0.79, P = 0.009) and TMIE (HR: 0.82, P = 0.003) as compared with OE. Conclusion: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, whereas both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer

Kepler-14b: A massive hot Jupiter transiting an F star in a close visual binary

We present the discovery of a hot Jupiter transiting an F star in a close visual (03 sky projected angular separation) binary system. The dilution of the host star's light by the nearly equalmagnitude stellar companion (∼0.5mag fainter) significantly affects the derived planetary parameters, and if left uncorrected, leads to an underestimate of the radius and mass of the planet by 10% and 60%, respectively. Other published exoplanets, which have not been observed with high-resolution imaging, could similarly have unresolved stellar companions and thus have incorrectly derived planetary parameters. Kepler-14b (KOI-98) has a period of P = 6.790 days and, correcting for the dilution, has a mass of Mp = 8.40+0.35 -0.34 M J and a radius of Rp = 1.136+0.073 -0.054 R J, yielding a mean density of ρp = 7.1 ± 1.1 g cm-3

K2 Discovers a Busy Bee: An Unusual Transiting Neptune Found in the Beehive Cluster

Open clusters have been the focus of several exoplanet surveys, but only a few planets have so far been discovered. The Kepler spacecraft revealed an abundance of small planets around small cool stars, therefore, such cluster members are prime targets for exoplanet transit searches. Kepler's new mission, K2, is targeting several open clusters and star-forming regions around the ecliptic to search for transiting planets around their low-mass constituents. Here, we report the discovery of the first transiting planet in the intermediate-age (800 Myr) Beehive cluster (Praesepe). K2-95 is a faint (K_p = 15.5 mag) M3.0 ± 0.5 dwarf from K2's Campaign 5 with an effective temperature of 3471 ± 124 K, approximately solar metallicity and a radius of 0.402 ± 0.050 R⊙. We detected a transiting planet with a radius of 3.47^(+0.78)_(-0.53) R⊕ and an orbital period of 10.134 days. We combined photometry, medium/high-resolution spectroscopy, adaptive optics/speckle imaging, and archival survey images to rule out any false-positive detection scenarios, validate the planet, and further characterize the system. The planet's radius is very unusual as M-dwarf field stars rarely have Neptune-sized transiting planets. The comparatively large radius of K2-95b is consistent with the other recently discovered cluster planets K2-25b (Hyades) and K2-33b (Upper Scorpius), indicating systematic differences in their evolutionary states or formation. These discoveries from K2 provide a snapshot of planet formation and evolution in cluster environments and thus make excellent laboratories to test differences between field-star and cluster planet populations