Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer.

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.

Surgical impact of bilateral transient occlusion of uterine and utero-ovarian arteries during laparoscopic myomectomy.

The objective of this article is to compare the amount of intraoperative blood loss during laparoscopic myomectomy when performing bilateral transient clamping of the uterine and utero-ovarian arteries versus no intervention. It´s a randomized controlled prospective study carried out in the Department of Obstetrics and Gynecology Ramón y Cajal University Hospital and HM Montepríncipe-Sanchinarro University Hospital, Madrid, Spain, in women with fibroid uterus undergoing laparoscopic myomectomy. Eighty women diagnosed with symptomatic fibroid uterus were randomly assigned to undergo laparoscopic myomectomy without additional intervention (Group A) or temporary clamping of bilateral uterine and utero-ovarian arteries prior to laparoscopic myomectomy (Group B). Estimated blood loss, operating time, length of hospital stay, and postoperative hemoglobin values were compared in both groups. The number of fibroids removed was similar in both groups (p = 0.77). Estimated blood loss was lower in the group of patients with prior occlusion of uterine arteries (p = 0.025) without increasing operating time (p = 0.17) nor length of stay (p = 0.17). No patient had either intra or postoperative complications. Only two patients (2.5%) required blood transfusion after surgery. We conclude that temporary clamping of bilateral uterine arteries prior to laparoscopic myomectomy is a safe intervention that reduces blood loss without increasing operative time.

Game of Crowns: Na+ Is Coming! Red NIR-Emissive Hybrid Liquid Crystals Containing Discotic Crown Ethers and Na2Mo6X8iCl6 (Xi = Cl or Br).

Molecular or supramolecular materials that can self-organize into columns such as discotic liquid crystals are of interest for several applications in the field of optoelectronics. We show in this work that red near-infrared (NIR)-emissive metal cluster compounds of general formula Na2Mo6X8iCl6 (Xi = Cl or Br) can be readily complexed with discotic liquid crystals containing a crown ether. Three cavity sizes have been tested with crown ethers bearing 4, 5, or 6 oxygen atoms. In all cases, 1:1 complexes were formed, thanks to the well-known supramolecular interactions existing between the Na+ cations of the metal cluster salt and the crown ether derivatives. All obtained hybrids are homogeneous, emit in the red NIR region, and show liquid crystalline properties on a wider temperature range than their precursors. Charge transport properties have been investigated by using a space charge limited current device. Obtained results demonstrate that metal cluster compounds can enhance the charge carrier mobility by 5 orders of magnitude compared to the native discotic organic ligands. Considering that the presented organic crown ether derivatives are not the best candidates to design optoelectronic devices because of their inherently low conductivity, but that similar compounds were developed to design proton conductive porous framework, our results open promising perspectives for the use of metal cluster compounds in devices dedicated to such a field.

Monitoring of metals and metalloids from maternal and cord blood samples in a population from Seville (Spain).

Nowadays there is an increasing concern about exposition during prenatal stage to environmental pollutants such as metals, that make pregnant women a vulnerable group of population. Numerous studies have shown associations between the prenatal exposition to some metals and an impact on cognitive, motor and intellectual development of the child. Metals and metalloid are ubiquitous in the environment and pregnant women are exposed to them though their diet, lifestyle factors or occupational and environmental sources. One hundred of maternal and one hundred of cord blood samples were obtained at delivery from pregnant women after signing of the informed consent to determine simultaneously levels of Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Se and Zn by ICP-MS. Among these metals, essential ones (Cu, Mn, Se and Zn) can have health beneficial effects at low levels, however, in high concentration are potentially toxic. On the other hand, elements such as Al, As, Cd, Hg, Pb are classified as toxic metals, no matter what its concentration was. The aim of this study was to find the potential relationships between these metals and metalloid levels, newborn's parameters, pregnancy details and the epidemiologic information obtained using a questionnaire data from the participant pregnant women from Seville (Spain). A n = 100 of participants have been enrolled, 15.6 % of the women from Virgen del Rocio Hospital were smokers during pregnancy but only 11.1 % from Virgen de Valme had the habit. Dietary habits of all participants from both hospital were quite similar in average rice, fish and canned food consumption. The characteristics of newborns were also quite similar for both hospitals. A positive correlation between maternal and cord blood was found between all metals except for Cr and Cu. The strongest correlation was found for Hg (r = 0.779, p < 0.005). Positive but weaker correlations between maternal blood and lifestyle habits were also established.

Joint Venture of Metal Cluster and Amphiphilic Cationic Minidendron Resulting in Near Infrared Emissive Lamellar Ionic Liquid Crystals.

Inorganic red-NIR emissive materials are particularly relevant in many fields like optoelectronic, bioimaging or solar cells. Benefiting from their emission in devices implies their integration in easy-to-handle materials like liquid crystals, whose long-range ordering and self-healing abilities could be exploited and influence emission. Herein, we present red-NIR emissive hybrid materials obtained with phosphorescent octahedral molybdenum cluster anions electrostatically associated with amphiphilic guanidinium minidendrons. Polarized optical microscopy and X-ray analysis show that while the minidendron chloride salts self-organize into columnar phases, their association with the dianionic metal cluster leads to layered phases. Steady-state and time-resolved emission investigations demonstrate the influence of the minidendron alkyl chain length on the phosphorescence of the metal cluster core.

Nutritional Quality of the Most Consumed Varieties of Raw and Cooked Rice in Spain Submitted to an In Vitro Digestion Model.

Rice is one of the most consumed staple foods around the world and its trade is highly globalized. Increased environmental pollution generates a large amount of waste that, in many cases, is discarded close to culture fields. Some species are able to bioaccumulate toxic substances, such as metals, that could be transferred to the food chain. The main goal of this study was to evaluate the content of metallic (Al, Cd, Pb, and Cr) and metalloid elements (As) in 14 of the most consumed varieties of rice in Spain and their effects on human health. The samples were cooked, and human digestion was simulated by using a standard in vitro digestion method. Metallic and metalloid element levels were analysed by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), previous called microwave digestion. Both the human health risk index, Hazard Quotient, and Lifetime Cancer Risk did not show toxic values in any case. Rice with a higher non-digestible fraction showed a higher liberation of proteins and a lower glycemic index. There were no significant differences in the concentrations of metallic and metalloid elements in cooked rice or in the digestible fraction in all varieties analysed. However, Al concentrations were higher than other metals in all varieties studied due to its global distribution. No relationship has been observed between the digestibility of rice and the bioaccessibility of each metallic and metalloid element. All of the studied rice varieties are healthy food products and its daily consumption is safe. The regular monitoring of metals and As in rice consumed in Spain may contribute to improvements in the human health risk evaluation.

Systematic Analysis of the Crystal Chemistry and Eu3+ Spectroscopy along the Series of Double Perovskites Ca2LnSbO6 (Ln = La, Eu, Gd, Lu, and Y).

Eu3+ (1 mol %)-doped Ca2LnSbO6 (replacing Ln3+; Ln = Lu, Y, Gd, and La) and Ca2EuSbO6 were synthesized and structurally characterized by means of X-ray powder diffraction. The Eu3+ luminescence spectroscopy of the doped samples and of Ca2EuSbO6 has been carefully investigated upon collection of the excitation/emission spectra and luminescence decay curves of the main excited states. Surprisingly, apart from the dominant red emission from 5D0, all the doped samples show an uncommon blue and green emission contribution from 5DJ (J = 1, 2, and 3). This is made possible thanks to both multiphonon and cross-relaxation mechanism inefficiencies. However, the emission from 5D3 is more efficient and the decay kinetics of the 5DJ (J = 0, 1, and 2) levels is slower in the case of Y- and Lu-based doped samples. This evidence can find a possible explanation in the crystal chemistry of this family of double perovskites: our structural investigation suggests an uneven distribution of the Eu3+ dopant ions in Ca2YSbO6 and Ca2LuSbO6 hosts of the general A2BB'O6 formula. The luminescent center is mainly located in the A crystal site, and on average, the Eu-Eu distances are longer than in the case of the Gd- and La-based matrix. These longer distances can further reduce the efficiency of the cross-relaxation mechanism and, consequently, the radiative transitions are more efficient. The slower depopulation of Eu3+ 5D2 and 5D1 levels in Ca2YSbO6 and Ca2LuSbO6 hosts is reflected in the longer rise observed in the 5D1 and 5D0 decay curves, respectively. Finally, in Ca2EuSbO6, the high Eu3+ concentration gives rise to an efficient cross-relaxation within the subset of the lanthanide ions so that no emission from 5DJ (J = 1, 2, and 3) is possible and the 5D0 decay kinetics is faster than for the doped samples.

Super-quadratic upconversion luminescence among lanthanide ions.

We explore the arguably most fundamental aspect of energy-transfer upconversion (ETU), namely the dependence of upconversion luminescence from a higher-energy level, following ETU excitation from a metastable lower-energy level, on direct luminescence from that metastable level. We investigate ETU among neighboring Nd3+ ions in single crystals of GdVO4 and LaSc3(BO3)4 with different doping concentrations by measuring, after short-pulse laser excitation with different pump energies, the infrared luminescence decay from the metastable 4F3/2 level and the yellow upconversion luminescence decay from the 4G7/2 level. We observe a highly super-quadratic dependence of upconversion on direct luminescence intensity. We conclude that the commonly assumed quadratic law of ETU, as proposed by Grant's model and frequently employed in rate-equation simulations, is inadequate to the description of ETU processes. Whereas Zubenko's model, which considers a finite migration rate, provides significantly better fits to the experimental luminescence-decay curves, also this model cannot accurately reproduce the measured decay curves, partly because it does not take the non-homogeneous distribution of active ions into account.

Consumer Motivation in Developed Economies With Secular Stagnation.

In recent years, the slow pace of economic growth, high indebtedness, and high unemployment registered in most developed economies since 2009 have revived the debate over the "secular stagnation hypothesis" first formulated by the Keynesian economist Alvin Hansen in 1938. This return of the secular stagnation hypothesis occurred in November 2013, when Lawrence Summers postulated that the global economy was facing a scenario of low growth, low inflation, and a reduction in GDP per capita due to a chronic insufficiency of aggregate demand. The causes should be sought not only in cyclical factors associated with a long financial cycle and excessive accumulated public and private debt, but also in structural changes in the central economies in recent decades, linked to the rapid slowdown in population growth and the gradual aging of the population. Finally, other factors also depress demand, such as the progressive exhaustion of the globalization process and the consolidation of new labor models. In light of these developments, this paper's aim is twofold: first, to perform an econometric panel-data study in order to determine the influence of each of these factors in explaining secular stagnation in recent years for the selected sample of countries; and, second, to lay out proposals for reorienting the government intervention strategies adopted since the onset of the financial crisis to promote consumption and achieve sustained growth, job creation, and poverty reduction.

Outcomes after Hysteroscopic Treatment of Symptomatic Isthmoceles in Patients with Abnormal Uterine Bleeding and Pelvic Pain: A Prospective Case Series.

BACKGROUND: Isthmoceles are described as complications associated with caesarean section (CS). Only symptomatic isthmoceles should be treated. The main symptoms are abnormal uterine bleeding (AUB) in the absence of any other causes, pelvic pain and secondary infertility. There are several techniques described for the correction of isthmoceles. Isthmoplasty can be performed by hysteroscopy, laparoscopy or vaginal surgery. The aim of this study was to assess the effectiveness of hysteroscopic surgical treatment of isthmoceles in women with associated symptoms such as pelvic pain and AUB. MATERIALS AND METHODS: A prospective case series study was performed; this study included all women with AUB, pelvic pain and ultrasonographic (US) diagnosis of isthmocele, who had undergone hysteroscopic correction between June 2014 and December 2017 in our Hospital. RESULTS: Thirty eight women underwent surgical hysteroscopy for correction of symptomatic isthmoceles. All patients presented AUB, 42.1% experienced pelvic pain and 28.9% had secondary infertility. US evaluation of isthmoceles was performed using 2D ultrasound. The residual myometrial thickness (RMT) above the isthmocele was measured in women who expected future pregnancy; if it was <2.5 mm the patient was not included in the study because the correction was performed laparoscopically. Follow-up was performed one and two months after the surgery. In all cases, pelvic pain was resolved one month after the surgery. AUB disappeared within the first month in 87.5% of patients and in the second month in 96.8% of subjects; however, one patient needed further surgery to alleviate her symptoms. Secondary infertility was assessed one year after surgical isthmoplasty. Seven women completed the first year of follow up, and three of them (42.8%) reported pregnancy after treatment between six and eight months after the surgery. CONCLUSION: Hysteroscopic correction of symptomatic isthmoceles may constitute a safe and effective technique for patients who present AUB and pelvic pain.

Disorder-Induced Breaking of the Local Inversion Symmetry in Rhombohedral Pyrochlores M2La3Sb3O14 (M = Mg or Ca): A Structural and Spectroscopic Investigation.

A detailed investigation of the overall crystal structure, and in particular of the local structure around the cations in M2La3Sb3O14 (M = Mg, Ca) was accomplished using X-ray diffraction, steady state luminescence spectroscopy and decay kinetics, and state of the art density functional calculations. The computational tool was also used to investigate the structure of Mn2La3Sb3O14. The Eu3+ dopant ion was employed as an optical probe of the local symmetry at the cationic sites. The use of these complementary techniques shows that the antimonates under investigation belong to the rhombohedral pyrochlore family with space group R3̅ m (No. 166), but while Mg2La3Sb3O14 and Mn2La3Sb3O14 show an ordered cationic configuration, the Ca2+ and La3+ of Ca2La3Sb3O14 are disordered because of their similar ionic radii. In both the Mg- and the Ca-based compounds, the Eu3+ ions formally occupy centrosymmetric sites, but in the case of Ca2La3Sb3O14 the presence of disorder in the outer coordination spheres removes the local inversion symmetry in these sites. This has a strong influence on the Eu3+ luminescence spectrum and on the radiative decay rate of the 5D0 emitting level.

CCL11, a novel mediator of inflammatory bone resorption.

Normal bone homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts is perturbed by inflammation. In chronic inflammatory disease with disturbed bone remodelling, e.g. rheumatoid arthritis, patients show increased serum levels of the chemokine eotaxin-1 (CCL11). Herein, we demonstrate an inflammatory driven expression of CCL11 in bone tissue and a novel role of CCL11 in osteoclast migration and resorption. Using an inflammatory bone lesion model and primary cell cultures, we discovered that osteoblasts express CCL11 in vivo and in vitro and that expression increased during inflammatory conditions. Osteoclasts did not express CCL11, but the high affinity receptor CCR3 was significantly upregulated during osteoclast differentiation and found to colocalise with CCL11. Exogenous CCL11 was internalised in osteoclast and stimulated the migration of pre-osteoclast and concomitant increase in bone resorption. Our data pinpoints that the CCL11/CCR3 pathway could be a new target for treatment of inflammatory bone resorption.

Assessing the Growth of Ethical Banking: Some Evidence from Spanish Customers.

Aristotle, who, having predated Adam Smith by 2000 years, deserves to be recognized as the world's first economist (Solomon, 1995), distinguished between two different senses of what we call economics: oikonomikos, or household trading, which he approved of and considered essential to the working of any even slightly complex society, and chrematisike, or trade for profit, which he considered selfish and utterly devoid of virtue, calling those who engaged in such practices "parasites". Of course, consumers do not purchase and invest for solely economic reasons (Polanyi, 1944). Interest in ethics in economics has been the subject of continuous study. In this regard, the recent financial crisis has had not only economic, but also social, psychological, political, and ethical consequences, which have impacted the financial and banking system. Consumers are no longer drawn only by the economic return but also by ethical factors. Ethical banking is on the rise. This paper aims to explain the reasons for the growth in ethical banking and to answer the following questions: can banking consumers-investors change the characterization of the banking system? Can ethical banking gain ground on traditional banking? And is ethical banking really effective? To this end, it will examine the Spanish case, using econometric causal regression models to identify the reasons why consumers decide to invest in ethical banking and determine its role in the Spanish economy.

SOCS3 deletion promotes optic nerve regeneration in vivo.

Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.