Mesothelioma Cells Escape Heat Stress by Upregulating Hsp40/Hsp70 Expression via Mitogen-Activated Protein Kinases

Therapy with hyperthermal chemotherapy in pleural diffuse malignant mesothelioma had limited benefits for patients. Here we investigated the effect of heat stress on heat shock proteins (HSP), which rescue tumour cells from apoptosis. In human mesothelioma and mesothelial cells heat stress (39–42°C) induced the phosphorylation of two mitogen activated kinases (MAPK) Erk1/2 and p38, and increased Hsp40, and Hsp70 expression. Mesothelioma cells expressed more Hsp40 and were less sensitive to heat stress compared to mesothelial cells. Inhibition of Erk1/2 MAPK by PD98059 or by Erk1 siRNA down-regulated heat stress-induced Hsp40 and Hsp70 expression and reduced mesothelioma cell survival. Inhibition of p38MAPK by SB203580 or siRNA reduced Hsp40, but not Hsp70, expression and also increased mesothelioma cell death. Thus hyperthermia combined with suppression of p38 MAPK or Hsp40 may represent a novel approach to improve mesothelioma therapy

The Changing Role of Ancillary Health Care Service Providers: An Evaluation of Health Diagnostic Laboratory, Inc.

In an effort to reduce cost and improve quality, health care payers have enacted a number of incentives to motivate providers to focus their efforts on achieving better clinical outcomes and reducing the prevalence and progression of disease. In response to these incentives, providers are entering into new arrangements such as accountable care organizations and patient-centered medical homes to redesign delivery processes and achieve quality and cost objectives. This article reports the results of a study designed to evaluate the impact on cost and quality of care resulting from services provided by Health Diagnostic Laboratory, Inc., a clinical laboratory with a comprehensive care model. The results show that patients who utilized these laboratory services experienced lower total cost of care (23% reduction, P \u3c 0.01) and improved lipid profiles during the follow-up period. Total cost reductions were related to cost reductions found in both inpatient and ambulatory care. These findings suggest that accountable care organizations, patient-centered medical homes, and other groups entering shared savings initiatives should consider the potential role ancillary service providers with comprehensive care models can play in the delivery of integrated care. (Population Health Management 2014; 17: 121-126

Is Preoperative Patient-Reported Health Status Associated with Mortality after Total Hip Replacement?

The influence of comorbidities and worse physical status on mortality following total hip replacement (THR) leads to the idea that patient-reported health status may also be a predictor of mortality. The aim of this study was to investigate the relationship between patient-reported health status before THR and the risk of dying up to 5 years post-operatively. For these analyses, we used register data on 42,862 THR patients with primary hip osteoarthritis operated between 2008 and 2012. The relative survival ratio was calculated by dividing the observed survival in the patient group by age- and sex-adjusted expected survival of the general population. Pre-operative responses to the five EQ-5D-3L (EuroQol Group) dimensions along with age, sex, education status, year of surgery, and hospital type were used as independent variables. Results shown that, as a group, THR patients had a better survival than the general population. Broken down by the five EQ-5D-3L dimensions we observed differentiated survival patters. For all dimensions, those reporting extreme problems had higher mortality than those reporting moderate or no problems. In conclusion, worse health status according to the EQ-5-3L before THR is associated with higher mortality up to five years after surgery. EQ-5D-3L responses may be useful in a multifactorial individualized risk assessment before THR.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Three Small Planets Transiting a Hyades Star

We present the discovery of three small planets transiting K2-136 (LP 358 348, EPIC 247589423), a late K dwarf in the Hyades. The planets have orbital periods of $7.9757 \pm 0.0011$, $17.30681^{+0.00034}_{-0.00036}$, and $25.5715^{+0.0038}_{-0.0040}$ days, and radii of $1.05 \pm 0.16$, $3.14 \pm 0.36$, and $1.55^{+0.24}_{-0.21}$ $R_\oplus$, respectively. With an age of 600-800 Myr, these planets are some of the smallest and youngest transiting planets known. Due to the relatively bright (J=9.1) host star, the planets are compelling targets for future characterization via radial velocity mass measurements and transmission spectroscopy. As the first known star with multiple transiting planets in a cluster, the system should be helpful for testing theories of planet formation and migration.Comment: Accepted to The Astronomical Journa

Exoplanets around Low-mass Stars Unveiled by K2

We present the detection and follow-up observations of planetary candidates around low-mass stars observed by the K2 mission. Based on light-curve analysis, adaptive-optics imaging, and optical spectroscopy at low and high resolution (including radial velocity measurements), we validate 16 planets around 12 low-mass stars observed during K2 campaigns 5-10. Among the 16 planets, 12 are newly validated, with orbital periods ranging from 0.96-33 days. For one of the planets (K2-151b) we present ground-based transit photometry, allowing us to refine the ephemerides. Combining our K2 M-dwarf planets together with the validated or confirmed planets found previously, we investigate the dependence of planet radius $R_p$ on stellar insolation and metallicity [Fe/H]. We confirm that for periods $P\lesssim 2$ days, planets with a radius $R_p\gtrsim 2\,R_\oplus$ are less common than planets with a radius between 1-2$\,R_\oplus$. We also see a hint of the "radius valley" between 1.5 and 2$\,R_\oplus$ that has been seen for close-in planets around FGK stars. These features in the radius/period distribution could be attributed to photoevaporation of planetary envelopes by high-energy photons from the host star, as they have for FGK stars. For the M dwarfs, though, the features are not as well defined, and we cannot rule out other explanations such as atmospheric loss from internal planetary heat sources, or truncation of the protoplanetary disk. There also appears to be a relation between planet size and metallicity: those few planets larger than about 3 $R_\oplus$ are found around the most metal-rich M dwarfs.Comment: 29 pages, 21 figures, 6 tables, Accepted in Astronomical Journa

Neto1 Is a Novel CUB-Domain NMDA Receptor–Interacting Protein Required for Synaptic Plasticity and Learning

The N-methyl-D-aspartate receptor (NMDAR), a major excitatory ligand-gated ion channel in the central nervous system (CNS), is a principal mediator of synaptic plasticity. Here we report that neuropilin tolloid-like 1 (Neto1), a complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing transmembrane protein, is a novel component of the NMDAR complex critical for maintaining the abundance of NR2A-containing NMDARs in the postsynaptic density. Neto1-null mice have depressed long-term potentiation (LTP) at Schaffer collateral-CA1 synapses, with the subunit dependency of LTP induction switching from the normal predominance of NR2A- to NR2B-NMDARs. NMDAR-dependent spatial learning and memory is depressed in Neto1-null mice, indicating that Neto1 regulates NMDA receptor-dependent synaptic plasticity and cognition. Remarkably, we also found that the deficits in LTP, learning, and memory in Neto1-null mice were rescued by the ampakine CX546 at doses without effect in wild-type. Together, our results establish the principle that auxiliary proteins are required for the normal abundance of NMDAR subunits at synapses, and demonstrate that an inherited learning defect can be rescued pharmacologically, a finding with therapeutic implications for humans

Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓

A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions at √s=7  TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101  TeV/c2 and MLQ(B0→e±μ∓)>126  TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds