Mass diffusion and Soret coefficient measurements of triethylene glycol/water binary mixtures by dynamic shadowgraphy.

The investigation of the transport properties of binary fluid mixtures remains a topic of interest in relation to the more challenging studies of ternary mixtures. In fact, the study of the phase boundary limits of the Gibbs composition triangle can be the initial step for a more complete analysis of ternary mixtures. In this paper, we apply the dynamic shadowgraphy optical technique to study non-equilibrium fluctuations induced by the presence of a gradient of temperature and/or concentration in the triethylene glycol (TEG)/water system. These thermodiffusion and free-diffusion experiments aim at measuring the transport properties of samples of the studied system at different experimental conditions. We scan both the average temperature and the TEG concentration, which allows us investigating both positive and negative thermodiffusive behaviours. The obtained values of mass diffusion coefficient are consistent with data available in the literature in the range of temperature investigated in this study. The mass diffusion coefficient of the sample prepared at 0.7 w/w TEG concentration are characterised by shadowgraphy following the two proposed methods, exhibiting consistent results. An increase of the mass diffusion coefficient as a function of the average temperature is highlighted. On the other hand, the thermodiffusion coefficient appears to be independent of the average temperature of the sample at 0.3 w/w TEG concentration.

Coupled non-equilibrium fluctuations in a polymeric ternary mixture.

We investigate by dynamic shadowgraphy the non-equilibrium fluctuations at the steady state of a thermodiffusion experiment in a polymeric ternary mixture of polystyrene-toluene-n-hexane. The structure function of the refractive index reveals the existence of quite different decay times, thus requiring the analysis of a wide range of correlation times. This is related to the simultaneous presence of three distinct decay modes corresponding to (from fastest to slowest) the relaxation of temperature fluctuations, of the concentration fluctuations of the mixed solvent, and of the concentration fluctuations of the polymer in the binary solvent. An investigation of the decay times at the corresponding diffusive regimes provides a measurement of the thermal diffusivity and the two eigenvalues of the mass diffusion matrix of the ternary mixture. Similar experiments were performed in the past but here, to suppress the confinement effect and obtain a more direct comparison with the theory, a thicker sample is studied. Moreover, also a faster camera is used allowing the experimental observation of faster modes, like the propagative ones. The experimental values of the decay times are eventually compared with those predicted by different available theories. Finally, we present a more complete theoretical model to describe the non-equilibrium fluctuations in the bulk of a ternary mixture at the steady state of a thermodiffusion experiment.

Preliminary analysis of Diffusion Coefficient Measurements in ternary mIXtures 4 (DCMIX4) experiment on board the International Space Station.

In the frame of the Diffusion Coefficient Measurements in ternary mIXtures 4 (DCMIX4) project the thermodiffusion experiments were conducted on the International Space Station (ISS) in the Selectable Optical Diagnostics Instrument (SODI) which is on orbit since 2009. We describe the results of the preliminary analysis of images downloaded during the execution of DCMIX4 in order to check the quality of the running experiments and, if needed, adjust the experiment parameters for the following runs. The quick analysis of raw data showed that they are meaningful and will allow to obtain the transport coefficients of examined ternary and binary mixtures.

European Space Agency experiments on thermodiffusion of fluid mixtures in space.

This paper describes the European Space Agency (ESA) experiments devoted to study thermodiffusion of fluid mixtures in microgravity environment, where sedimentation and convection do not affect the mass flow induced by the Soret effect. First, the experiments performed on binary mixtures in the IVIDIL and GRADFLEX experiments are described. Then, further experiments on ternary mixtures and complex fluids performed in DCMIX and planned to be performed in the context of the NEUF-DIX project are presented. Finally, multi-component mixtures studied in the SCCO project are detailed.

bFGF interaction and in vivo angiogenesis inhibition by self-assembling sulfonic acid-based copolymers.

The antiangiogenic activity of different families of biocompatible and non-toxic polymer drugs based on 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or polymethacrylic derivatives of 5-aminonaphthalen sulfonic acid (MANSA) is analyzed using directed in vivo angiogenesis assay and correlated with in vitro results. These active compounds were copolymerized with butylacrylate (BA) and N-vinylpyrrolidone in order to obtain two families of copolymers with different properties in aqueous media. The most hydrophobic copolymers poly(BA-co-MANSA) and poly(BA-co-AMPS) formed amphiphilic copolymers and presented micellar morphology in aqueous media. This supramolecular organization of the copolymers had a clear effect on bioactivity. Poly(BA-co-MANSA) copolymers showed the best antiangiogenic activity and very low toxicity at relatively low dose, with the possibility to be injected directly in the solid tumors alone or in combination with other therapeutic agents such as anti-VEGF drugs. The obtained results demonstrate that not only the chemical structure but also the supramolecular organization of the macromolecules plays a key role in the anti-angiogenic activity of these active polymers.

Impact of outbreak COVID-19 pandemic on psychiatry emergencies in Spain.

The SARS-CoV-2 pandemic has caused an unprecedented clinical situation. A retrospective cross-sectional study was designed with the aim to evaluate psychiatric emergencies from March 14 to May 1, 2020, coinciding with the start of the emergency state and the lockdown until the attenuation of the confinement. Data obtained during this period were compared with the emergencies attended in the same period of 2019. A total of 213 psychiatric emergencies were attended in 2020 compared with 367 in 2019. The mean number of emergencies per day was significantly lower during the COVID-19 outbreak in 2020 (M=4.35, SD= 2.04) vs. the same period in 2019 (M=7.50, SD= 3.18). A higher percentage of patients with schizo/psychotic disorders (34.3% in 2020, vs. 24.3% in 2019), as well as a lower percentage of patients with anxiety/adaptive disorders (25.4% in 2020 vs. 35.4% in 2019) was observed during the outbreak. A significant lower mean discharge/emergency ratio (M=42.17, SD= 26.94 in 2020 vs. M=63.43, SD= 17.64 in 2019) and a higher referral to Internal Medicine/emergency ratio (M=20.55, SD= 22.16 in 2020 vs. M=3.32, SD= 6.63 in 2019) was observed. The results suggest important changes in psychiatric emergencies during the most critical period of the COVID-19 outbreak in Spain.

Structure, morphology, and bioactivity of biocompatible systems derived from functionalized acrylic polymers based on 5-amino-2-naphthalene sulfonic acid.

New therapeutic strategies for the treatment of neoplastic pathologies and, in particular, metastasis processes are based on the inhibitory effect of angiogenic processes. The present article deals with the design, preparation, and application of new "polymer drugs" with a clear inhibitory effect of the activation of fibroblast growth factors, which plays an important role in the proliferation of vascular cells and, consequently, in tumor angiogenesis. Two different copolymer systems based on 5-methacrylamide-2-naphthalenesulfonic acid (MANSA) and butylacrylate (BA) or vinylpyrrolidone (VP) were prepared by free radical copolymerization and exhaustively characterized. The molecular weight of the copolymers was moderate but both families presented very homogeneous macromolecular populations with a polydispersity index very close to unity, which indicates that MANSA presents a noticeable effect on the polymerization processes. The system poly(BA-co-MANSA) provides amphiphilic copolymers that give rise to the formation of oriented micelles with a core of the hydrophobic BA segments and a shell of MANSA components. The average size of these self-assembling nanoparticles is between 20 and 100 nm, depending on the composition of the copolymer system. However, poly(VP-co-MANSA) systems are more hydrophilic and give more homogeneous and water-soluble macromolecules. The bioactivity of both systems was studied by the analysis of proliferation of Balb/c 3T3 fibroblasts in the presence of acidic fibroblast growth factor (aFGF) as a function of the concentration of poly(BA-co-MANSA) or poly(VP-co-MANSA), and the results obtained demonstrated that the MANSA-containing polymers were not toxic for cells, but induced a clear inhibition of cell proliferation in the presence of aFGF. The effect was polymer-concentration dependent, but the activity was noticeably higher for poly(BA-co-MANSA) copolymers, owing to the self-assembled micellar morphology of the nanoparticles, which placed the sulfonic groups in the more adequate position to interact with the growth factor. These systems offer a good alternative for low toxicity treatments of angiogenic, processed based on inhibition of the activity of growth factors.

MCCB cognitive profile in Spanish first episode schizophrenia patients.

The objective of the study was to examine the cognitive profile of Spanish patients with a first episode of schizophrenia (FESz) and to compare that to the profile of patients with a chronic schizophrenia (CSz) and non-psychiatric (NP) control subjects. The study included 106 FESz, 293 CSz, and 210 NP, assessed with the Spanish version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB cognitive profile in a Spanish sample of FESz was similar to the cognitive profile of CSz with some discrepancies in select domains. The scores of both patient samples were about 1-2 SD below the scores of non-psychiatric control subjects.

Identification of a thyroid hormone response element in the promoter region of the rat lipocalin-type prostaglandin D synthase (beta-trace) gene.

We have previously reported that mRNA levels for the rat lipocalin-type prostaglandin (PG) D synthase/beta-trace (PGDS) gene, the enzyme responsible for the production of PGD2 in the central nervous system, are regulated by thyroid hormone in vivo. In this study, we describe the identification of a thyroid hormone (T3) response element (T3RE) in the 5'-flanking region of the rat PGDS gene. By radioimmunoprecipitation of genomic fragments using thyroid hormone receptor (TR) protein and specific anti-TR antibodies, gel-shift, foot-printing, mutational analysis, and transactivation assays we have identified a spaced four imperfect direct repeat (DR4) element, GGTTCACTTCAGGGTA (positions -586/-571), which functions as a T3RE when fused to a heterologous promoter. Our results suggest that thyroid hormone regulates the expression of the rat lipocalin-type PGDS gene through this element. Remarkably, the element identified also confers regulation by retinoic acid. Giving the important roles proposed for the PGDS enzyme and its product, PGD2, the major PG in the mammalian brain, the altered expression of the PGDS gene may contribute to the deleterious effects of hypothyroidism in the central nervous system.

PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity.

BACKGROUND AND PURPOSE: PM01183 is a new synthetic tetrahydroisoquinoline alkaloid that is currently in phase I clinical development for the treatment of solid tumours. In this study we have characterized the interactions of PM01183 with selected DNA molecules of defined sequence and its in vitro and in vivo cytotoxicity. EXPERIMENTAL APPROACH: DNA binding characteristics of PM01183 were studied using electrophoretic mobility shift assays, fluorescence-based melting kinetic experiments and computational modelling methods. Its mechanism of action was investigated using flow cytometry, Western blot analysis and fluorescent microscopy. In vitro anti-tumour activity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the in vivo activity utilized several human cancer models. KEY RESULTS: Electrophoretic mobility shift assays demonstrated that PM01183 bound to DNA. Fluorescence-based thermal denaturation experiments showed that the most favourable DNA triplets providing a central guanine for covalent adduct formation are AGC, CGG, AGG and TGG. These binding preferences could be rationalized using molecular modelling. PM01183-DNA adducts in living cells give rise to double-strand breaks, triggering S-phase accumulation and apoptosis. The potent cytotoxic activity of PM01183 was ascertained in a 23-cell line panel with a mean GI(50) value of 2.7 nM. In four murine xenograft models of human cancer, PM01183 inhibited tumour growth significantly with no weight loss of treated animals. CONCLUSIONS AND IMPLICATIONS: PM01183 is shown to bind to selected DNA sequences and promoted apoptosis by inducing double-strand breaks at nanomolar concentrations. The potent anti-tumour activity of PM01183 in several murine models of human cancer supports its development as a novel anti-neoplastic agent.

[Quality of life evaluation in spinal cord injured patients comparing different bladder management techniques]. / Evaluación de la calidad de vida en pacientes con lesión medular comparando diferentes métodos de vaciado vesical.

OBJECTIVES: This study examines quality of life among patients with spinal cord injury requiring bladder management techniques, according to the validated King s Health Questionnaire (KHQ). MATERIAL AND METHODS: Prospective and observational study of 91 spinal cord-injured patients (21 women 23% and 70 men 77%). Mean age was 40 years (SD 13.4) and average time since spinal injury was 11.4 (SD 10.4) years. Patients completed the KHQ quality of life instrument and 10 additional questions related to urinary disturbance developed for the study, and filled in a form to subjectively rank their main concerns related to spinal injury. Patients were divided according to the bladder management techniques they regularly used: intermittent catheterization, condom catheter or indwelling catheter, and differences between the mean groups were assessed with de SPSS 13.0 statistic package. RESULTS: The overall KHQ score for the sample was 39.9 (SD 54.4) with higher scores (poorer QoL) in patients using an indwelling catheter. A thorough analysis of the test showed no significant differences between the groups other than in the physical role limitation item (p

Brain-specific prostaglandin D2 synthetase mRNA is dependent on thyroid hormone during rat brain development.

We have previously described several cDNA clones whose expression is affected by thyroid hormone during rat brain development. We now report the identification of one of these, the E2 clone, as the brain-specific prostaglandin D2 (PGD2) synthetase gene. Sequence comparison shows a nearly complete identity between the 356 nucleotides of the E2 clone and nucleotides 403 to 759 of PGD2 synthetase cDNA. The pattern of E2 expression corresponds to that expected for brain specific PGD2 synthetase gene, i.e. the corresponding mRNA is not detected in any other tissue analyzed apart of the brain, and it was present at different levels in all brain regions. Hypothyroidism decreased E2 mRNA concentrations in cerebral cortex and cerebellum. Control of the level of expression of PGD2 synthetase gene may contribute the complex effects of thyroid hormone on brain development and function.

Establishment and characterisation of a human carcinoma cell line with acquired resistance to Aplidin.

Aplidin (APL) is a new antitumoral drug from marine origin currently in phase II clinical trials against a wide multiplicity of cancers. As resistance may be, as with other drugs, an important obstacle to the APL therapeutic efficacy, we have established an acquired resistance cellular model by continuous exposure of HeLa cells to the drug. The stably resistant subline generated (HeLa-APL), possessing more than 1000-fold relative resistance to APL than parental cells, did not show crossresistance to a subset of clinically relevant antitumoral agents. In addition, resistance was not related to overexpression of P-glycoprotein or differences in overall drug accumulation. Comparing to parental cells, HeLa-APL cells did not present either significant differences in the growth rate or apparent alterations in the cell cycle distribution. Aplidin induced rapid and persistent phosphorylation of both JNK and p38 MAPKs, resulting in activation of the mitochondrial apoptotic pathway in parental cells, but, notably, in HeLa-APL-resistant cells MAPKs activation only occurred in a slight and transiently manner, failing to activate the above-mentioned apoptotic machinery. These results suggest that sustained activation of JNK and p38 is essential for triggering the apoptotic programme induced by APL and that HeLa-APL cells bypass this apoptotic response by preventing the specific mechanisms that prime and sustain the long-term activation of these signalling cascades. Although far from human tumour physiology in vivo, HeLa-APL cells represent a potentially useful tool in gaining insights into the mode of action of APL, in selecting non-crossresistant APL structural analogues, as well as in investigating and developing methods to prevent resistance to this drug.

Hypothyroidism alters the expression of prostaglandin D2 synthase/beta trace in specific areas of the developing rat brain.

Lipocalin-type prostaglandin D2 synthase is the enzyme responsible for the synthesis of prostaglandin D2, a major prostaglandin in the central nervous system. We analysed the effects of thyroid hormone deprivation on prostaglandin D2 synthase gene expression in the developing rat brain. By in situ hybridization, the strongest prostaglandin D2 synthase mRNA signal was detected in the leptomeninges and choroid plexus. The signal was greatly reduced in the cerebellar interlaminar meninges of hypothyroid rats aged 15 and 25 days. Immunohistochemical studies defined changes in the location of the prostaglandin D2 synthase protein. In control but not in hypothyroid animals, Cajal-Retzius neurons of cortical layer I, and pyramidal cortical plate neurons were intensely stained on postnatal day 5. Conversely, prostaglandin D2 synthase protein levels were higher in neurons of the CA1 and CA3 regions and the dentate gyrus of the hippocampus of hypothyroid animals on postnatal days 5, 15 and 25, and also in subplate neurons on postnatal days 15 and 25. In agreement with the in situ hybridization and northern blotting data, the major difference was found in the cerebellar interlaminar meninges of hypothyroid animals, where the protein was clearly down-regulated on postnatal days 15 and 25. These results show that hypothyroidism causes both age- and region-specific alterations in the expression and location of the prostaglandin D2 synthase during postnatal brain development, probably reflecting a cell-specific regulatory effect of thyroid hormone on the prostaglandin D2 synthase.

Intraspinal baclofen in the treatment of severe spasticity and spasms.

Ten patients with severe spasticity were evaluated according to a standardized protocol in order to be treated by intraspinal baclofen. Entry criteria in the protocol were the following: 1) Stable central nervous system lesion, 2) Severe spasticity and/or flexo-extensor spasms not controllable by oral treatment, 3) Normal CSF circulation and 4) Informed consent. All patients received a test dose of twenty-five micrograms of baclofen injected intrathecally. At intervals of at least one day, doses were increased in 10-25 microgram steps until total abolition of spontaneous spasms was achieved in complete spinal cord lesions. In patients with residual motor function, doses were titrated until the optimal dose was found that reduced spasms and enabled performance of maximum daily life activities according to the patient's neurological level. In nine patients a multidose reservoir was implanted to deliver intrathecal baclofen. Effective dosage was 60 +/- 31 micrograms in the entire group. Ashworth score was reduced from 4.6 +/- 0.7 to 1.2 +/- 0.4 (mean +/- SD) (p less than 0.0001) and spasms from 3.2 +/- 0.8 to 0.2 +/- 0.4 (p less than 0.0001). Follow-up of the nine patients in whom a reservoir was implanted has been 18 +/- 9 months. Initial dosage requirements and tolerance were significantly different in complete (Frankel's A grade) or incomplete lesions (Frankel's B, C and D grades). Complete spinal cord lesions required a greater initial dose (156 +/- 43) than incomplete lesions (44 +/- 24), these differences being statistically significant (Student's t-test, p less than 0.05). Tolerance was observed only in patients with complete motor and complete sensory lesions. In incomplete lesions, dose increase was insignificant.

Dexamethasone induces lipocalin-type prostaglandin D synthase gene expression in mouse neuronal cells.

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the production of PGD(2), the main PG in the CNS. PGD(2) is an endogenous sleep inducer, and it is involved in the control of odor and pain responses and body temperature. In addition, PGD synthase transports lipophilic molecules in the subarachnoid space and CSF. By northern and western assays we show that the synthetic glucocorticoid dexamethasone, an inhibitor of PG production in most tissues, induces L-PGDS mRNA and protein in a dose- and time-dependent fashion in mouse neuronal GT1-7 cells. Accordingly, dexamethasone increases cellular L-PGDS enzymatic activity. Dexamethasone induced L-PGDS gene transcription in run-on assays and activated the mouse L-PGDS gene promoter in transiently transfected cells. It is interesting that the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA), which induces the synthesis of PGs in many tissues, inhibited the increase in L-PGDS expression induced by dexamethasone. In contrast, neither dexamethasone nor TPA affected the expression of cyclooxygenases-1 and -2. Our data demonstrate that dexamethasone induces L-PGDS gene transcription in neuronal cells.

Retinoic acid and 1,25-dihydroxyvitamin D3 inhibit tenascin-C expression in rat glioma C6 cells.

Tenascin-C (Tn-C) is an extracellular matrix protein with growth-, invasive-, and angiogenesis-promoting activities. Tn-C is upregulated during wound healing, tumorigenesis, and other pathological conditions. Highly malignant gliomas with poor prognosis exhibit high levels of Tn-C expression. Here we demonstrate that Tn-C RNA expression in glioma C6 cells is inhibited in a dose-dependent manner by retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-D3). No additive or synergistic effects were found. Inhibition is maximum 24 hr after RA or 1,25-D3 treatment, prior to a delayed cytotoxic effect starting at day 4-5 of treatment, and correlates with a reduction in the synthesis of Tn-C protein. Tn-C expression is also inhibited, but to a lesser extent by prostaglandin D2 (PGD2). Furthermore, both RA and 1,25-D3, but not PGD2 abolish the induction of Tn-C by the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate. The inhibition of Tn-C expression might be relevant for the anti-cancer activity of RA and 1,25-D3.

Traumatic spinal cord injury complicating ankylosing spondylitis.

The aim of this paper is to review the incidence and characteristics found in traumatic spinal cord injury (SCI) occurring in patients with long-standing ankylosing spondylitis (AS). The incidence of patients with traumatic SCI admitted to our unit from January 1984 to February 1996 was 2% (15 out of 893). They were all men with a mean age of 56 years. Most frequently the etiology of the lesion was a motor vehicle accident and the injury was mainly due to a hyperextension mechanism. Acute spinal fracture occurred in 13 patients, all involving the cervical region. No fracture was observed in two patients with thoracic neurological level. Three patients presented with an interval free period of neurological symptoms in whom a spinal epidural hematoma was visualized with magnetic resonance imaging. On admission eight patients were diagnosed as having complete SCI and the other seven an incomplete SCI. In the acute phase, respiratory complications were most frequent, causing six patients to die. Treatment was conservative in 14 patients. Multidisciplinary management of these patients should be implemented in an institution equipped with both a Spinal Injury Unit and an Intensive Care Unit.

Identification and localization of a nucleolin homologue in onion nucleoli.

A protein homologous to nucleolin, a major nucleolar protein with multifunctional features involved in pre-rRNA synthesis and early processing, has been identified and localized in situ in onion root meristematic cells by different techniques, which have included the use of an antibody raised against hamster nucleolin. The protein was identified on Western blots of nucleolar proteins as a 64-kDa band, by means of the anti-nucleolin antibody, bismuth staining, and the silver staining-nucleolar organizer (Ag-NOR) method. The experiments also suggested that nucleolin could be a target of these two cytochemical stainings. Although the 64-kDa band corresponds to a major nucleolar protein, it is a minor one among total nuclear proteins. The same techniques were used in situ at the ultrastructural level, and the immunogold detection of the nucleolin homologue was quantitatively evaluated. The protein accumulates in the transition area from nucleolar fibrillar centers to the dense fibrillar component, which is considered to be the structural result of ribosomal gene transcription. Out of this transition area, the dense fibrillar component may be divided into two regions, proximal and distal with respect to fibrillar centers, which show, respectively, the significant and unsignificant presence of nucleolin; we interpret this fact as the expression of the topological arrangement of pre-rRNA processing. Fibrillar centers themselves showed a weak but significant labeling with the anti-nucleolin antibody. However, bismuth staining was absent from the interior of fibrillar centers, indicating that the nucleolin in them is not phosphorylated. Ag-NOR staining uniformly covered fibrillar centers and the dense fibrillar component (at least in its proximal region), but it did not stain condensed chromatin inclusions in heterogeneous fibrillar centers, showing that the binding of nucleolin to chromatin is associated with its decondensation. This work provides additional evidence of the high phylogenetic conservation of molecular motifs which take part in ribosome biogenesis.