Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP). / Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP).

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings. / BIOBADATOP: Registro Español de Dermatitis Atópica. Descripción y primeros resultados.

BACKGROUND: In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. MATERIALS AND METHOD: The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). RESULTS: We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine. CONCLUSIONS: Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD.

Dynamics and rheology of a suspension of super-paramagnetic chains under the combined effect of a shear flow and a rotating magnetic field.

This study presents an analysis of the dynamics of single and multiple chains of spherical super-paramagnetic beads suspended in a Newtonian fluid under the combined effect of an external rotating magnetic field and a shear flow. Viscosity results depend on two main non-dimensional numbers: the ratio between the shear rate and the magnetic rotation frequency and the ratio between the hydrodynamic and magnetostatic interactions (the Mason number). When the shear rate is smaller than the magnetic field frequency, the chain rotation accelerates the surrounding fluid, reducing the value of the measured suspension viscosity even below that of the solvent. In this regime, shear-thickening is observed. For values of the shear rates comparable to the rotation magnetic frequency, the viscosity reaches a maximum and non-linear coupling effects come up. If the shear rate is increased to values above the rotation frequency, the viscosity decreases and a mild shear-thinning is observed. In terms of the Mason number, the suspension viscosity reduces in line with the literature results reported for fixed magnetic fields, whereas the shear-rate/magnetic-frequency ratio parameters induce a shift of the viscosity curve towards larger values. Results at larger concentrations and multiple chains amplify the observed effects.

A real-time XAS PEEM study of the growth of cobalt iron oxide on Ru(0001).

The growth of mixed cobalt-iron oxides on Ru(0001) by high-temperature oxygen-assisted molecular beam epitaxy has been monitored in real time and real space by x-ray absorption photoemission microscopy. The initial composition is a mixed Fe-Co(II) oxide wetting layer, reflecting the ratio of the deposited materials. However, as subsequent growth of three dimensional spinel islands nucleating on this wetting layer takes place, the composition of the oxide in the wetting layer changes as iron is transferred into the spinel islands. The composition of the islands themselves also changes during growth.

Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.

UNLABELLED: Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. INTRODUCTION: Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. METHODS: Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. RESULTS: C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. CONCLUSIONS: Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies utilizing mice as preclinical models for osteoporosis.

Novel chiral magnetic domain wall structure in Fe/Ni/Cu(001) films.

Using spin-polarized low energy electron microscopy, we discovered a new type of domain wall structure in perpendicularly magnetized Fe/Ni bilayers grown epitaxially on Cu(100). Specifically, we observed unexpected Néel-type walls with fixed chirality in the magnetic stripe phase. Furthermore, we find that the chirality of the domain walls is determined by the film growth order with the chirality being right handed in Fe/Ni bilayers and left handed in Ni/Fe bilayers, suggesting that the underlying mechanism is the Dzyaloshinskii-Moriya interaction at the film interfaces. Our observations may open a new route to control chiral spin structures using interfacial engineering in transition metal heterostructures.

Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

Phototherapy, classic systemic treatments (methotrexate, acitretin, and ciclosporin), and biologic agents (etanercept, infliximab, adalimumab, and ustekinumab) constitute a broad therapeutic arsenal that increases the likelihood of achieving control of severe and extensive disease in patients with psoriasis. Acitretin continues to be a very valuable tool in both monotherapy, in which it is combined with other systemic treatments (classic or biologic), and in sequential therapy. Thanks to its lack of a direct immunosuppressive effect and its ability to achieve a long-term response, acitretin has an important role in the treatment of psoriasis, although this has not always been acknowledged in relevant treatment guidelines. We present consensus guidelines for the use of acitretin in psoriasis drawn up by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. These guidelines provide a detailed account of acitretin, including pharmacological properties, indications and contraindications, adverse effects, and factors that should be taken into account to enhance the safe use of this drug. They also propose treatment strategies for use in routine clinical practice. The overall aim of these guidelines is to define the criteria for the use and management of acetretin in psoriasis.

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer.

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.

Multidisciplinary approach to the study of large-format oil paintings.

Cultural heritage has become a keystone for comprehending our society, as it represents and reflects our origins, passions, beliefs and traditions. Furthermore, it provides fundamental information about specific temporary spaces, materials' availability, technology, artist's intention, and site weather conditions. Our aim was to develop a multidisciplinary approach with a main focus on investigating two Italian large-format paintings located in highly diverse environments such as the National Theater of Costa Rica. We monitored environmental conditions and quantified fungal aerial spores. Then, we determined regions of possible biodeterioration with the software MicroorganismPattern and used the software PigmentArrangement to elucidate the apparent colour of the paintings based on distribution and arrangement of the pigment crystals. Finally, we characterized eight genera of calcareous nannofossils found in the ground layers of the artwork. The former Men's Canteen at the National Theater of Costa Rica presented a mean air temperature of 23.5 [Formula: see text]C, a relative humidity of 72.7% and a concentration of CO[Formula: see text] of 570 ppm. The fungal aerial concentration was 1776 spores/m[Formula: see text]. The software MicroorganismPattern identified 32 sampling regions, out of which 11 were positive for microbial contamination. The software PigmentArrangement determined that the blue crystals (ultramarine pigment) had the shortest distances between themselves (29 [Formula: see text]m). Finally, the nanofossils identified enabled us to restrict the age of the material to a biostratigraphic interval ranging from Coniacian to Maastricthian ages. By using a multidisciplinary approach we were able to explore the diptych, suggest a set of minimally invasive perspectives in tropical environments to be used worldwide and obtain key information about the artist's artistic process, materials used along with better understand its state of conservation.

Chemotherapy-induced nausea and vomiting in clinical practice: impact on patients' quality of life.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) in cancer patients are common symptoms most feared by patients. The aim of this study was to analyze the impact of CINV associated to moderate/highly emetogenous chemotherapy regimens on patients' quality of life (QoL). PATIENTS AND METHODS: Open, multicenter, prospective observational study was performed. Each patient filled out a patient diary for each cycle from the day before chemotherapy and for the next 5 days that included the number of emetic episodes, the intensity of nausea, and QoL evaluation (functional living index-emesis questionnaire). RESULTS: Data from 202 consecutive patients from nine university hospitals were collected, but only data from 160 were analyzed (79.2 %). Most of the participants (70 %) were women with a mean age of 50 years (SD 1.2 years). The most frequent cancer site was breast (44 %) followed by lung (16 %) and 76.3 % were receiving highly emetogenous chemotherapy. Despite the use of antiemetic prophylaxis, patients experienced significant nausea and vomiting during 31 % (3.2 % during acute, 15.0 % during delayed phase, and 13.2 % during both phases) and 45.1 % (5.1 % only during the acute phase, 23.5 % only during the delayed phase and 16.5 % during both phases) of the cycles, respectively, having 44.5 % (nausea) and 39.3 % (emesis) of the cycles an impact on patients' QoL. CONCLUSIONS: The results of the study confirm the detrimental effect of CINV on patients' QoL despite the use of antiemetic prophylaxis (5HT(3) receptor antagonist, steroids, and dopamine receptor antagonists). It is mandatory to intensify the detection of CINV in order to improve the management of these important, albeit frequent, side effects of cancer treatments.

A re-evaluation of the mitogenic effect of serotonin on vascular endothelial cells.

Serotonin is an extracellular mediator recognized by seven different types of receptors, thus giving rise to pleiotropic intracellular responses. One of these responses is the activation of proliferation for a number of cell types. The induction of proliferation of otherwise quiescent endothelial cells is a key step of angiogenesis. Previously published work concerning the effect of serotonin on endothelial cell proliferation is controversial. The present work is aimed to re-evaluate the mitogenic role of serotonin on endothelial cells, since a pro-angiogenic role for serotonin could be hypothesized if its mitogenic potential on these cells were confirmed. By using three different types of endothelial cells and three experimental approaches, we demonstrate that serotonin cannot be considered a general mitogen for endothelial cells.

[Meduloblastoma: infrequent onset in local recurrence]. / Meduloblastoma: una presentación infrecuente en la recurrencia local.

INTRODUCTION. Meduloblastoma is high potential to recur and spread tumour. CASE REPORT. One case posterior fosse meduloblas toma in six years old boy who received 3 surgeries, chemotherapy and radiotherapy, with local recurrence and extracranial extension into neck laterocervical musculature. CONCLUSION. Although meduloblastoma extraneural metastases are not isolated phenomenon, meduloblastoma extracraneal extension is uncommon phenomenon in local recurrence.

[Occult anterior sacral meningocele]. / Meningocele sacro anterior oculto.

BACKGROUND: The anterior sacral meningocele is a rare form of spinal dysraphism located in the presacral extraperitoneal space. It is generally asymptomatic and appears as a small pelvic mass. CASE DESCRIPTION: We present a case of a 10 year-old male that develops a bacteria meningitis because of a pararectal abscess that is connected with an anterior sacral meningocele. We successfully treated it using a posterior approach. CONCLUSION: The aim of the surgery is to repair the dural defect and to obliterate the communication between the thecal sac and the herniation defect. The posterior approach is the simplest and most effective surgical technique because the lower risk of neurological injury than the anterior approach.

[Level of empowerment of hospitalized chronic heart failure patient].

BACKGROUND: Establishing the level of chronic cardiac inpatient empowerment is essential. By doing so, it is possible to identify groups with a lower level. It also provides a basis for designing effective strategies to improve their control over decision making and the actions that affect their health and wellness. The shortage of studies of this phenomenon for this particular population and context suggests that such patients are not receiving proper care. METHODS: A prospective and descriptive study was carried out. A validated Spanish version of the Patient empowerment in long-term conditions scale was used. The survey has 47 items, grouped into three dimensions: Positive attitude and feeling of control, Knowledge in shared decision making, and Seeking information and sharing with other patients. It was distrib-uted 24 hours before hospital discharge. RESULTS: Twenty five questionnaires were collected (81%). The mean global empowerment score of the patients was 165.92 ± 20.9. The dimension Positive attitude and sense of control showed the lowest score, with a mean of 3.4 ± 0.5. An inverse weak relationship was found between the level of empowerment and age (rho = -0.240; p = 0.000) while a positive one was found with 10-year survival (rho = 0,316; p = 0.01). CONCLUSION: The level of empowerment of the patients in this study was medium-high. The strategies used to address the care of this population should focus on working on their attitude towards the disease and perceived control of the situation, and should be individualized according to age.

[Pediatric intensive care after brain tumor surgery]. / Postoperatorio de tumores cerebrales en la unidad de cuidados intensivos pediátricos.

INTRODUCTION: Primary brain tumors are the most common solid tumors in children. Surgery is the basis of treatment for these patients, who require postoperative admission to the ICU-P. The aim of this study was to at the epidemiology of brain tumors of patients admitted to our ICU-P and to analyze the progress of these children in the postoperative period. PATIENTS AND METHODS: Retrospective-prospective study of children admitted to our unit after brain tumor surgery between January 1998 and January 2007. We collected information such as, personal details, clinical characteristics, type of intervention and postoperative period. RESULTS: We reviewed 161 postoperative periods, corresponding to 134 patients (54.5% male). The mean age was 7 years and 8 months +/- 5 months. The most common location was the posterior fossa (44.8%). The most common histological type was low grade/intermediate astrocytoma (44.7%). The most frequent complication was diabetes insipidus (9.9%). Resection was complete in 58.4% patients. The median stay in the ICU-P was 2 days (0-61 days). 3 patients died after surgery. CONCLUSIONS: The epidemiology of the group of patients admitted to our ICU-P is similar to the general population. The most common complication is diabetes insipidus.

[Environmental Guarantees in the Constitution: a new ecological-political model for Costa Rica and the rest of the world]. / Garantías Ambientales en la Constitución: un nuevo modelo ecológico-político para Costa Rica y el resto del mundo.

In the last thirty years significant changes to protect the environment have been introduced in the judicial, administrative and social systems. Costa Rica is a well known international model in the field of sustainable development, and here I present a proposal for adding environmental gaurantees to the Costa Rican Constitution. One of the most important changes in the Costa Rican judicial system has been the introduction of an environmental amendment in the Constitution (Article 50). However, it is still fundamental to introduce a Title of Environmental Guarantees in the Constitution of Costa Rica, with these components: first, the State, the public and the private sector have the duty of defending the right to a safe environment; second, public domain over environmental issues, and third, the use of the environment should be regulated by scientific and technical knowledge. If current efforts succeed, Costa Rica will be the first country in the world to include Environmental Guarantees in its Constitution. This would be an example to other nations.

Spatial-temporal survey of Microcystis oligopeptide chemotypes in reservoirs with dissimilar waterbody features and their relation to genetic variation.

The ability of cyanobacteria to produce toxins and other secondary metabolites is patchily distributed in natural populations, enabling the use of cellular oligopeptide compositions as markers to classify strains into ecologically-relevant chemotypical subpopulations. The composition and spatiotemporal distribution of Microcystis chemotypes within and among waterbodies was studied at different time scales by analyzing (i) Microcystis strains isolated between 1998 and 2007 from different Spanish reservoirs and (ii) individual Microcystis aeruginosa colonies collected from pelagic and littoral habitats in Valmayor reservoir (Spain) during a bloom. No agreement between chemotypes and both morphotypes and genotypes (based on cpcBA-IGS, 16S-23S rRNA ITS and mcyB genes) was found, suggesting that oligopeptide profiles in individual strains evolve independently across morphospecies and phylogenetic genotypes, and that the diversity of microcystin variants produced cannot be explained by mcyB gene variations alone. The presence of identical chemotypes in spatially-distant reservoirs with dissimilar trophic state, lithology or depth indicate that waterbody characteristics and geographical boundaries weakly affect chemotype composition and distribution. At smaller spatiotemporal scales (i.e. during bloom), M. aeruginosa populations showed high number of chemotypes, as well as marked differences in chemotype composition and relative abundance among the littoral and pelagic habitats. This indicates that the factors influencing chemotype composition, relative abundance and dynamics operate at short spatial and temporal scales, and supports emerging hypotheses about interactions with antagonistic microorganisms as possible drivers for widespread chemical polymorphisms in cyanobacteria.

Phase singularity point tracking for the identification of typical and atypical flutter patients: A clinical-computational study.

Atrial Flutter (AFL) termination by ablating the path responsible for the arrhythmia maintenance is an extended practice. However, the difficulty associated with the identification of the circuit in the case of atypical AFL motivates the development of diagnostic techniques. We propose body surface phase map analysis as a noninvasive tool to identify AFL circuits. Sixty seven lead body surface recordings were acquired in 9 patients during AFL (i.e. 3 typical, 6 atypical). Computed body surface phase maps from simulations of 5 reentrant behaviors in a realistic atrial structure were also used. Surface representation of the macro-reentrant activity was analyzed by tracking the singularity points (SPs) in surface phase maps obtained from band-pass filtered body surface potential maps. Spatial distribution of SPs showed significant differences between typical and atypical AFL. Whereas for typical AFL patients 70.78 ±â€¯16.17% of the maps presented two SPs simultaneously in the areas defined around the midaxialliary lines, this condition was only satisfied in 5.15 ±â€¯10.99% (p < 0.05) maps corresponding to atypical AFL patients. Simulations confirmed these results. Surface phase maps highlights the reentrant mechanism maintaining the arrhythmia and appear as a promising tool for the noninvasive characterization of the circuit maintaining AFL. The potential of the technique as a diagnosis tool needs to be evaluated in larger populations and, if it is confirmed, may help in planning ablation procedures.

Strontium hexaferrite platelets: a comprehensive soft X-ray absorption and Mössbauer spectroscopy study.

Platelets of strontium hexaferrite (SrFe12O19, SFO), up to several micrometers in width, and tens of nanometers thick have been synthesized by a hydrothermal method. They have been studied by a combination of structural and magnetic techniques, with emphasis on Mössbauer spectroscopy and X-ray absorption based-measurements including spectroscopy and microscopy on the iron-L edges and the oxygen-K edge, allowing us to establish the differences and similarities between our synthesized nanostructures and commercial powders. The Mössbauer spectra reveal a greater contribution of iron tetrahedral sites in platelets in comparison to pure bulk material. For reference, high-resolution absorption and dichroic spectra have also been measured both from the platelets and from pure bulk material. The O-K edge has been reproduced by density functional theory calculations. Out-of-plane domains were observed with 180° domain walls less than 20 nm width, in good agreement with micromagnetic simulations.