Repetitive patterns in rapid optical variations in the nearby black-hole binary V404 Cygni.

How black holes accrete surrounding matter is a fundamental yet unsolved question in astrophysics. It is generally believed that matter is absorbed into black holes via accretion disks, the state of which depends primarily on the mass-accretion rate. When this rate approaches the critical rate (the Eddington limit), thermal instability is supposed to occur in the inner disk, causing repetitive patterns of large-amplitude X-ray variability (oscillations) on timescales of minutes to hours. In fact, such oscillations have been observed only in sources with a high mass-accretion rate, such as GRS 1915+105 (refs 2, 3). These large-amplitude, relatively slow timescale, phenomena are thought to have physical origins distinct from those of X-ray or optical variations with small amplitudes and fast timescales (less than about 10 seconds) often observed in other black-hole binaries-for example, XTE J1118+480 (ref. 4) and GX 339-4 (ref. 5). Here we report an extensive multi-colour optical photometric data set of V404 Cygni, an X-ray transient source containing a black hole of nine solar masses (and a companion star) at a distance of 2.4 kiloparsecs (ref. 8). Our data show that optical oscillations on timescales of 100 seconds to 2.5 hours can occur at mass-accretion rates more than ten times lower than previously thought. This suggests that the accretion rate is not the critical parameter for inducing inner-disk instabilities. Instead, we propose that a long orbital period is a key condition for these large-amplitude oscillations, because the outer part of the large disk in binaries with long orbital periods will have surface densities too low to maintain sustained mass accretion to the inner part of the disk. The lack of sustained accretion--not the actual rate--would then be the critical factor causing large-amplitude oscillations in long-period systems.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of abdominal ultrasound in inflammatory bowel disease. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el empleo de la ecografía abdominal en la enfermedad inflamatoria intestinal.

Ultrasound has an excellent diagnostic performance when Crohn's disease is suspected, when performing an activity assessment, or determining the extension and location of Crohn's disease, very similar to other examinations such as MRI or CT. It has a good correlation with endoscopic lesions and allows the detection of complications such as strictures, fistulas or abscesses. It complements colonoscopy in the diagnosis and, given its tolerance, cost and immediacy, it can be considered as a good tool for disease monitoring. In ulcerative colitis, its role is less relevant, being limited to assessing the extent and activity when it is not possible with other diagnostic techniques or if there are doubts with these. Despite its advantages, its use in inflammatory bowel disease (IBD) is not widespread in Spain. For this reason, this document reviews the advantages and disadvantages of the technique to promote knowledge about it and implementation of it in IBD Units.

Effects of mannoprotein E1 in liquid diet on inflammatory response and TLR5 expression in the gut of rats infected by Salmonella typhimurium.

BACKGROUND: Mannoproteins are yeast cell wall componend, and rich in mannose. The use of foods rich in mannose as carbohydrate, could have a bioprotective effect against entrobacteria intestinal infection. Nothing is known about mannoproteins' activity in inflammatory bowel processes induced by entrobacteria.This study investigates the effects of mannoprotein administration via a liquid diet on inflammatory response and TLR5 expression during intestinal tissue injury in a rat model of infection with Salmonella typhimurium. METHODS: Adult Wistar male rats were divided into three groups: control, and mannoprotein E1 at 10 or 15%. Animals were fed with a liquid diet supplemented or not with mannoprotein E1. Groups were infected by intragastrical administration of S. typhimurium. 24 h post-inoculation samples of spleen, ileum and liver were collected for microbiological studies. Gut samples were processed to determine levels of proinflammatory cytokines (mRNA) and TLR5 (mRNA and protein) by quantitative PCR and Western-blot, and the number of proliferative and apoptotic cells determined by immunohistochemistry. RESULTS: Ininfected levels of proinflammatory cytokines and TLR5 were higher in untreated controls than in the animals receiving mannoprotein. Proliferation was similar in both groups, whereas apoptosis was higher in controls. Curiosly, the mannoprotein effect was dose dependent. CONCLUSIONS: Mannoprotein administration in a liquid diet seems to protect intestinal tissue against S. typhimurium infection. This protection seems to expressed as a lower pro-inflammatory response and TLR5 downregulation in gut epithelium, as well as by an inhibition of apoptosis. Nevertheless, the molecular mechanism by which mannoprotein is able to regulate these responses remain unclear. These results could open up new avenues in the use of mannoproteins as prebiotics in the therapeutic strategy for treatment of inflammatory gut processes induced by microbia.

Communications: Evidence for the role of fluctuations in the thermodynamics of nanoscale drops and the implications in computations of the surface tension.

Test-area deformations are used to analyze vapor-liquid interfaces of Lennard-Jones particles by molecular dynamics simulation. For planar vapor-liquid interfaces the change in free energy is captured by the average of the corresponding change in energy, the leading-order contribution. This is consistent with the commonly used mechanical (pressure-tensor) route for the surface tension. By contrast for liquid drops, one finds a large second-order contribution associated with fluctuations in energy. Both the first- and second-order terms make comparable contributions, invalidating the mechanical relation for the surface tension of small drops. The latter is seen to increase above the planar value for drop radii of approximately 8 particle diameters, followed by an apparent weak maximum and slow decay to the planar limit, consistent with a small negative Tolman length.

Urinary bladder lipoma: an illustrative case.

Urinary bladder lipomas are rare neoplasms. Therefore, very few of them have been reported in the literature. We present a case that illustrates the typical features that allow radiologists to diagnose this entity: a solid lesion that arises from the urinary bladder wall, showing an endophytic growth and homogeneous hypoattenuation. After its surgical resection, the diagnosis was confirmed by anatomo-pathological analysis. In the discussion we describe other neoplasms that should also be considered when a submucosal bladder neoplasm is detected on computed tomography or other imaging techniques.

Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors.

Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti-programmed cell death protein-1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti-PD-1 agent might be a strategy to revert anti-PD-1 resistance.

Computation of surface tensions using expanded ensemble simulations.

A method for the direct simulation of the surface tension is examined. The technique is based on the thermodynamic route to the interfacial tension and makes use of the expanded ensemble simulation method for the calculation of the free energy difference between two inhomogeneous systems with the same number of particles, temperature, and volume, but different interfacial area. The method is completely general and suitable for systems with either continuous or discontinuous interactions. The adequacy of the expanded ensemble method is assessed by computing the interfacial tension of the planar vapor-liquid interface of Lennard-Jones, Lennard-Jones dimers, Gay-Berne, and square-well model fluids; in the latter, the interactions are discontinuous and the present method does not exhibit the asymmetry of other related methods, such as the test area. The expanded ensemble simulation results are compared with simulation data obtained from other techniques (mechanical and test area) with overall good agreement.

Estimating errors in free energy calculations from thermodynamic integration using fitted data.

A procedure to estimate the statistical uncertainties associated with free energies computed from thermodynamic integration using fitted data is described. The method involves generating synthetic data sets from the actual simulation data and performing an analysis of the resulting distribution of free energy values. These values follow a Gaussian distribution, and the corresponding standard deviation is associated with the error in the computed value of the free energy. The impact of these uncertainties on the coexistence pressure is examined for first-order transitions. The approach is demonstrated with an examination of finite-size effects at the freezing transition of hard spheres.

Vapor-liquid interfacial properties of fully flexible Lennard-Jones chains.

We consider the computation of the interfacial properties of molecular chains from direct simulation of the vapor-liquid interface. The molecules are modeled as fully flexible chains formed from tangentially bonded monomers with truncated Lennard-Jones interactions. Four different model systems comprising of 4, 8, 12, and 16 monomers per molecule are considered. The simulations are performed in the canonical ensemble, and the vapor-liquid interfacial tension is evaluated using the test area and the wandering interface methods. In addition to the surface tension, we also obtain density profiles, coexistence densities, critical temperature and density, and interfacial thickness as functions of temperature, paying particular attention to the effect of the chain length on these properties. According to our results, the main effect of increasing the chain length (at fixed temperature) is to sharpen the vapor-liquid interface and to increase the width of the biphasic coexistence region. As a result, the interfacial thickness decreases and the surface tension increases as the molecular chains get longer. The interfacial thickness and surface tension appear to exhibit an asymptotic limiting behavior for long chains. A similar behavior is also observed for the coexistence densities and critical properties. Our simulation results indicate that the asymptotic regime is reached for Lennard-Jones chains formed from eight monomer segments. We also include a preliminary study on the effect of the cutoff distance on the interfacial properties. Our results indicate that all of the properties exhibit a dependence with the distance at which the interactions are truncated, though the relative effect varies from one property to the other. The interfacial thickness and, more particularly, the interfacial tension are found to be strongly dependent on the particular choice of cutoff, whereas the density profiles and coexistence densities are, in general, less sensitive to the truncation.

A high-protein dietary treatment to intestinally hypotrophic rats induces ghrelin mRNA content and serum peptide level changes.

BACKGROUND & AIMS: Ghrelin is a peptide mainly secreted in stomach with a potent growth hormone releasing activity both in vitro and in vivo. The trophic mucosal effect of an enriched protein diet may be related with ghrelin and growth hormone plasma levels since peptides from the somatotrophic axis are well-known trophic factors. The possible relationship between nutritionally regulated active ghrelin plasma levels and the intestinal trophic effects of a high-protein diet was probed in rats with intestinal hypotrophy induced by an elemental diet. METHODS: Normal and elemental-diet-induced intestinally hypotrophic rats were treated with either a normoproteic or a high-protein diet for 1 week. It was determined ghrelin and IGF-1 plasma levels, fundic and duodenal ghrelin concentrations, ghrelin mRNA content and intestinal morphometric, proliferative and apoptotic parameters were determined. Growth hormone plasma levels were measured indirectly through IGF-1 plasma levels. RESULTS: Ghrelin plasma levels increased in elemental diet-induced intestinally hypotrophic rats fed either diet. Duodenum mRNA content, but not fundus, increased under the same conditions where plasma was studied. Dietary treatment did not modify the IGF-1 plasma levels. However, animals previously fed an elemental diet to induce intestinal hypotrophy had significantly lower levels of IGF-1. CONCLUSIONS: The trophic effects on the intestine of an enriched protein diet are associated with increased ghrelin serum peptide level and mRNA content, and this increase might be related to the IGF-1 plasma levels in elemental diet-induced intestinally hypotrophic rats.

Smectic phase in a system of hard ellipsoids with isotropic attractive interactions.

The smectic phase is studied for a thermotropic fluid model consisting of aligned hard ellipsoids with superimposed square-well attractive interactions of variable range. The system is analyzed using a density functional theory in which the hard-core contributions to the free-energy functional are treated within a nonlocal weighted density approximation and the attractive contributions are considered at a mean-field level. In the absence of attractions the model reduces, under appropriate scaling, to a fluid of hard spheres and therefore does not exhibit smectic ordering. It is shown that above a certain value of the square-well range, smectic ordering is stable relative to the nematic state at densities well inside the fluid region. The nematic-smectic-A transition is found to be continuous at high temperatures and first order at low temperatures, these two regimes being separated by a tricritical point at an intermediate temperature. These predictions have been confirmed by computer simulation of the model fluid. The results highlight that smectic ordering can be stabilized by coupling anisotropic short-range repulsions with the isotropic contribution of the soft attractive interactions. By increasing the pressure, the range of stability of the smectic phase is seen to decrease. At sufficiently high pressure, the smectic phase is suppressed, and the solid phase dominates. Our calculations show that smectic ordering is no longer stable if the range of the attractions is made too long ranged.

Density functional theory and simulation of the columnar phase of a system of parallel hard ellipsoids with attractive interactions.

A simple molecular model consisting of parallel hard oblate ellipsoids with superimposed square-well attractive interactions of variable range is considered for the study of the phase behavior of thermotropic discotic molecules. A density functional theory appropriate for nonuniform fluids is formulated in which the hard-core contributions to the free energy are treated within a nonlocal weighted-density approximation (WDA) while the attractive contributions are treated at a mean-field level. It is shown that the columnar phase becomes stable relative to the nematic phase at fluid densities for a range of values of the range of the attractive well. In these cases, the region of stability of the columnar phase is bounded at high temperatures by a nematic-columnar-solid triple point. The calculations show that if the attractions are made too long ranged (lambda/D> or approximately =0.84 for particles of aspect ratio of L/D=0.1, where lambda/D is the range of the attractive interaction in units of the molecular diameter D), columnar ordering becomes unstable and the nematic phase dominates at all fluid densities. It is shown that columnar ordering is also predicted when the density functional theory is supplemented with the smoothed-density approximation (SDA). Computer simulations have also been carried out for a particular choice of model parameters; our simulation data confirm the stabilization of the hexagonal columnar phase between the solid and nematic phases. A comparison with simulation data allows us to conclude that the WDA provides a fairly good description of the columnar phase and very good agreement for the nematic-columnar transition properties. On the other hand, our calculations show that the SDA largely underestimates the transition pressure and predicts a too-strongly first-order nematic-columnar transition

Growth Hormone Protects the Intestine Preserving Radiotherapy Efficacy on Tumors: A Short-Term Study.

The efficacy of radiotherapy on tumors is hampered by its devastating adverse effects on healthy tissue, particularly that of the gastrointestinal tract. These effects cause acute symptoms that are so disruptive to patients that they can lead to interruption of the radiotherapy program. These adverse effects could limit the intensity of radiation received by the patient, resulting in a sublethal dose to the tumor, thus increasing the risk of tumor resistance. The lack of an effective treatment to protect the bowel during radiation therapy to allow higher radiation doses that are lethal to the tumor has become a barrier to implementing effective therapy. In this study, we present a comparative analysis of both intestinal and tumor tissue in regard to the efficacy and the preventive impact of a short-term growth hormone (GH) treatment in tumor-bearing rats as a protective agent during radiotherapy. Our data show that the exogenous administration of GH improved intestinal recovery after radiation treatment while preserving the therapeutic effect against the tumor. GH significantly increased proliferation in the irradiated intestine but not in the irradiated tumors, as assessed by Positron Emission Tomography and the proliferative markers Ki67, cyclin D3, and Proliferating Cell Nuclear Antigen. This proliferative effect was consistent with a significant increase in irradiated intestinal villi and crypt length. Furthermore, GH significantly decreased caspase-3 activity in the intestine, whereas GH did not produce this effect in the irradiated tumors. In conclusion, short-term GH treatment protects the bowel, inducing proliferation while reducing apoptosis in healthy intestinal tissue and preserving radiotherapy efficacy on tumors.

Growth hormone protects against radiotherapy-induced cell death.

BACKGROUND: In vivo treatment with growth hormone reduces radiation-associated mortality. The molecular mechanisms underlying this effect are unknown. It has been described that increased sensitivity to ionising radiation can be due to defects in machinery involved in detection and/or repair of DNA double-strand breaks. OBJECTIVE: To study the mechanisms involved in growth hormone action on the increased survival in irradiated cells. MATERIALS AND METHODS: CHO-4 cells stably expressing the growth hormone receptor were used. A cell viability assay was carried out to analyse the increase in survival induced by growth hormone in irradiated cells. To investigate whether the DNA repair mechanism could be implicated in this effect we performed DNA reactivation assays using pHIV-LUC and pCMV-betagal plasmids as control. Identical studies were also conducted using the radiomimetic drug, bleomycin. RESULTS: Growth hormone protects CHO-4 cells from bleomycin- and radiation-induced cell death. In pHIV-LUC transfected cells, a time-dependent decrease in luciferase activity was observed after irradiation in the absence of growth hormone. However, cells pretreated with this hormone maintained reporter activity. When cells were transfected with irradiated pHIV-LUC plasmid, only the hormone-treated cells recovered the transcriptional activity. CONCLUSIONS: Growth hormone exerts a radioprotective effect in CHO-4 cells stably transfected with the complementary DNA for the rat growth hormone receptor. The radioprotection is triggered directly by the hormone and it is also observed with bleomycin. The increased survival in response to radiation and bleomycin treatment induced by growth hormone correlates with an enhanced ability of the cells to repair damaged DNA.

Protective effects of dietary enrichment with docosahexaenoic acid plus protein in 5-fluorouracil-induced intestinal injury in the rat.

OBJECTIVE: The intestinal side effects of anti-tumoural therapy can be so severe as to preclude its clinical efficacy, although the use of selected nutrients and growth factors may ameliorate the noxious effects. This study examines whether dietary supplementation with the polyunsaturated fatty acid docosahexaenoic acid (DHA) potentiates the protective action of growth hormone in the intestine and whether a synergetic effect occurs with dietary protein and DHA enrichment and growth hormone treatment. METHODS: Male Wistar rats were divided into nine groups and received a standard diet, or a diet supplemented with protein, or a diet supplemented with DHA, or a diet supplemented with both protein and DHA. Three days later, the rats were given 5-fluorouracil (5-FU) and treated with either growth hormone or placebo. A further group of animals fed a standard diet was not treated and served as a control group. Intestinal morphometry, proliferation and apoptosis were determined. RESULTS: Supplementing the diet with DHA prevented the negative action of 5-FU on mucosal morphometry, but protein supplementation was necessary to prevent the increased apoptosis. When growth hormone was also given with the dietary supplementation, the hypoproliferative effect of 5-FU was also prevented. CONCLUSION: Enriching the diet with DHA protects against intestinal lesions produced by the anti-tumoural drug 5-FU but requires the joint administration of supplementary protein and growth hormone to reduce the noxious effects of 5-FU.

Growth hormone protects the intestines but not the tumour from 5-fluorouracil toxicity in the short term in the rat.

OBJECTIVE: Growth hormone has been proposed as an effective preventative treatment against radiotherapy- and chemotherapy-induced toxicity in the gut. The aim of this study was to determine whether exogenously administered growth hormone modified the effect of 5-fluorouracil on the gut and an implanted colon adenocarcinoma in the rat METHODS: An adenocarcinoma was implanted into rats that had been treated with 5-fluorouracil and growth hormone 3 days previously. Tumour growth, plus tumour and intestinal pathology, proliferation, apoptosis and p53 expression were determined. RESULTS: Growth hormone protected the intestines against 5-fluorouracil by increasing proliferation and mucosal length, and decreasing apoptosis and p53 expression. Growth hormone did not modify the effects of 5-fluorouracil on the tumour. CONCLUSIONS: Growth hormone protects the intestines from the deleterious effects of 5-fluorouracil while preserving its antitumoural action on the adenocarcinoma in the short term. Within the crypt, p53 expression is likely to be modulated by growth hormone after 5-fluorouracil treatment.

[Prevalence of main cardiovascular risk factors in women from Biscay]. / Prevalencia de los principales factores de riesgo cardiovascular en mujeres de Vizcaya.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the prevalence of principal cardiovascular risk factors in the female population from Biscay (northern Spain). PATIENTS AND METHOD: We selected a random representative sample of 1,317 women aged between 16 and 65 years from this province. For each participant we recorded the following parameters: weight and height, physical activity, smoking, blood pressure, glycemia, total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol. RESULTS: A total of 1,100 women (mean age 39.83 14 years) participated. Regarding physical activity, 31.9% of the women had a sedentary lifestyle and 48.4% did not exercise during leisure time. The prevalence of smoking was 31.9%. We found a mean body mass index of 24.9 4.6 kg/m2, and 42.4% of the women were overweight. The prevalence of hypertension was 13.1%, hypertension being defined as a mean systolic blood pressure > or = 160 mmHg, diastolic blood pressure > or = 95 mmHg, current antihypertensive treatment, or any combination of these criteria. When a cutoff value of > or = 140/90 mmHg was used, the prevalence increased to 26.7%. Total cholesterol values were > or = 240 mg/dl in 26.2%, triglyceride levels were > or = 200 mg/dl in 2.6%, LDL-cholesterol was > or = 160 mg/dl in 26.8%, and HDL-cholesterol values were < 45 mg/dl in 12.2%. The prevalence of hyperglycemia was 3.3%. CONCLUSIONS: The prevalences of main cardiovascular risk factors were similar to those in other Spanish studies. Except for smoking, the rest of these risk factors increased with age. Long-term measures should be adopted to modify dietary habits and lifestyles to obtain improvements in the cardiovascular risk profile.

Growth hormone upregulates intestinal trefoil factor expression in the ileum of rats after γ-radiation.

Growth hormone (GH) and intestinal trefoil factor (ITF) have been involved in intestinal protection and repair. This study investigates the effects of GH administration on ITF expression and histological changes associated with tissue injury in an intestinal rat model of radiation. Adult male rats were divided into four groups: control, GH, radiation and radiation + GH (GHyRAD). Ileum samples were obtained at 2 or 72 h after radiation and processed to determine ITF levels (mRNA and protein) by quantitative polymerase chain reaction, Western blot and immunohistochemistry. In addition, goblet ITF-positive cells were identified by immunohistochemistry at 72 h. Our results showed an upregulation of mRNA and protein production of ITF in ileum samples after GH and radiation + GH compared with control and irradiated samples. Irradiation alone affected ITF protein expression. However, irradiation after GH pretreatment produced the highest ITF mRNA and protein levels at both the tested time points. ITF-producing goblet cells were identified in intestinal villi (apical location). GH treatment increased the number of ITF-producing goblet cells, and radiation after GH treatment displayed further increase in the number of ITF-positive goblet cells. GH upregulates ITF in normal intestinal tissue. This upregulation is higher when radiation is given after GH treatment. Nevertheless, the mechanism by which GH regulates ITF expression remains unclear and is still under investigation. These results could open up new avenues in the therapeutic reparative and protective effects of GH during radiotherapy and chemotherapy.

Exogenous ghrelin regulates proliferation and apoptosis in the hypotrophic gut mucosa of the rat.

Ghrelin is the natural endogenous ligand for growth hormone secretagogue receptors. This peptide regulates energy homeostasis and expenditure and is a potential link between gut absorptive function and growth. We hypothesized that ghrelin may induce a proliferative and antiapoptotic action promoting the recovery of the hypotrophic gut mucosa. Therefore, the aim of the study was to determine the action of exogenous ghrelin following gut mucosal hypotrophia in rats fed an elemental diet. An elemental diet provides readily absorbable simple nutrients and is usually given to patients with absorptive dysfunction. Male Wistar rats (n = 48) were fed the elemental diet for one week to induce mucosal hypotrophy and then treated for another week with systemic ghrelin and pair-fed with either a normoproteic or hyperproteic isocaloric liquid diet. Another group received a standard diet instead of the elemental diet and served as control (normotrophy). The elemental diet induced intestinal hypotrophia characterized by decreased proliferation in the ileum and increased apoptosis in jejunum and ileum. Ghrelin administration restored normal levels of proliferation in the ileum and apoptosis in the jejunum, with partial apoptosis restoration in the ileum. Ghrelin levels in plasma and fundus were increased in all groups, although the highest levels were found in rats treated with exogenous ghrelin. Ghrelin administration has a positive effect in the hypotrophic gut, regulating both proliferation and apoptosis towards a physiological balance counteracting the negative changes induced by an elemental diet in the intestines.