Predictors of Interstitial Lung Disease in Mixed Connective Tissue Disease.

Interstitial lung disease (ILD) frequently complicates mixed connective tissue disease (MCTD) and contributes to increased mortality. We aimed to identify predictors of ILD in MCTD patients. This is a nationwide, multicentre, retrospective study including patients with an adult-onset MCTD clinical diagnosis who met Sharp's, Kasukawa, Alarcón-Segovia, or Kahn's diagnostic criteria and had available chest high-resolution computed tomography (HRCT) data. Univariate and multivariate analyses were conducted. We included 57 MCTD patients, with 27 (47.4%) having ILD. Among ILD patients, 48.1% were asymptomatic, 80.0% exhibited a restrictive pattern on pulmonary function tests, and 81.5% had nonspecific interstitial pneumonia on chest HRCT. Gastroesophageal involvement (40.7% vs. 16.7%, p = 0.043) and lymphadenopathy at disease onset (22.2% vs. 3.3%, p = 0.045) were associated with ILD. Binary logistic regression identified lymphadenopathy at disease onset (OR 19.65, 95% CI: 1.91-201.75, p = 0.012) and older age at diagnosis (OR 1.06/year, 95% CI: 1.00-1.12, p = 0.046) as independent ILD predictors, regardless of gender and gastroesophageal involvement. This study is the first to assess a Portuguese MCTD cohort. As previously reported, it confirmed the link between gastroesophageal involvement and ILD in MCTD patients. Additionally, it established that lymphadenopathy at disease onset and older age at diagnosis independently predict ILD in MCTD patients.

Unexpected Primary Pleural Melanoma Simulating a Chest Wall Tumor

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Fundamentos del Diseño Universal para el Aprendizaje Desde la Perspectiva Internacional / Fundamentals of Universal Design for Learning from an International Perspective

RESUMEN: El presente estudio se enmarca en el ámbito educativo, concretamente, en el área de la educación inclusiva, profundizando en el Diseño Universal para el Aprendizaje (DUA). El DUA se concibe como un enfoque teórico y práctico que actúa como una herramienta eficaz para alcanzar una educación de calidad y equidad dentro del movimiento de la inclusión educativa. El objetivo de este estudio es analizar la presencia de los fundamentos del DUA (derecho de la educación; diversidad; Diseño Universal; currículo flexible; igualdad de oportunidades; neurociencia y tecnologías de la información y la comunicación) en los documentos publicados por los organismos internacionales con competencia en materia educativa y de repercusión mundial. La metodología de la investigación es de corte cualitativo utilizando el análisis documental. Las categorías de análisis corresponden a los siete fundamentos del DUA. Las fuentes documentales para el estudio han sido fundamentalmente las páginas web de los organismos internacionales y la base de datos UNESDOC, obteniéndose una muestra definitiva de once documentos pertenecientes a la literatura gris. Tras la revisión documental, los resultados han evidenciado que no todos los documentos objeto de estudio contemplan en su contenido las categorías de análisis. En suma, se observan carencias en cuanto a la presencia de los siete fundamentos del DUA en los documentos publicados analizados, por lo que se requiere de un nuevo tratamiento a nivel internacional del DUA con el fin de promover una educación de calidad e inclusiva, que atiende y respeta a las diferencias individuales dentro del proceso de enseñanza-aprendizaje.

ABSTRACT: The present study was carried out in the frame of the educational field, specifically in the area of​​inclusive education, going deeper into the Universal Design for Learning (UDL). UDL is conceived as a theoretical and practical approach that acts as an effective tool to achieve quality education and equity within the educational inclusion movement. The objective of this study is to analyze the presence of the fundamentals of UDL (education law; diversity; Universal Design; flexible curriculum; equal opportunities; neuroscience and information and communication technologies) in documents published by international organizations with competence in education and global impact. The research methodology is of a qualitative nature and uses documentary analysis. The categories of analysis correspond to the seven fundamentals of UDL. The documentary sources of the study were mainly the web pages of international organizations and the UNESDOC database, obtaining a definitive sample of eleven documents belonging to the gray literature. After the document review, the results showed that not all documents under study include the categories of analysis in their content. In summary, there are gaps in the presence of the seven fundamentals of UDL in the published documents analyzed, which is why a new international treatment of the UDL is needed to promote an inclusive and quality education that meets and respects individual differences within the teaching-learning process.

Vaginal residence and pharmacokinetic preclinical study of topical vaginal mucoadhesive W/S emulsions containing ciprofloxacin.

The aim of this work is to test the in vivo behavior of a mucoadhesive vaginal emulsion resistant to the clearance of vaginal fluids using ciprofloxacin (CPX) as an anti-infective model of drug. CPX is a broad-spectrum antibiotic used in the treatment of sexual tissues infections, as intravenous injection in a dose of 20 mg every 12 h. In this study, CPX was incorporated in water in silicone (W/S) mucoadhesive emulsions and the in vivo residence time and the CPX in vivo absorption and distribution to the sexual organs was studied using the rat as animal model. W/S emulsion shows excellent in vitro bioadhesion having high resistance to the vaginal fluids clearance. The drug release profiles show a constant release of CPX during at least 6 h according to a zero-order kinetics. In vivo computerized PET/CT Image Analysis after intravaginal administration to rats indicates that W/S emulsions remain in the vaginal area for a long time and shows a good absorption of the radiotracers used as markers through the vaginal mucosa. Ciprofloxacin pharmacokinetic studies developed after the single intravaginal administration of W/S emulsion shows a good absorption and distribution of CPX on the uterus and ovarian tissue. A significant concentration of CPX in the sexual tissues was observed after 24 h of administration of W/S emulsion. Therefore, W/S emulsions have a good in vivo residence and drug release in the vaginal mucosae showing a great potential for the treatment of sexual tissues infections, as vaginal bioadhesive delivery systems of antinfectious drugs.

Effect of roll compaction on granule size distribution of microcrystalline cellulose-mannitol mixtures: computational intelligence modeling and parametric analysis.

Dry granulation using roll compaction is a typical unit operation for producing solid dosage forms in the pharmaceutical industry. Dry granulation is commonly used if the powder mixture is sensitive to heat and moisture and has poor flow properties. The output of roll compaction is compacted ribbons that exhibit different properties based on the adjusted process parameters. These ribbons are then milled into granules and finally compressed into tablets. The properties of the ribbons directly affect the granule size distribution (GSD) and the quality of final products; thus, it is imperative to study the effect of roll compaction process parameters on GSD. The understanding of how the roll compactor process parameters and material properties interact with each other will allow accurate control of the process, leading to the implementation of quality by design practices. Computational intelligence (CI) methods have a great potential for being used within the scope of quality by design approach. The main objective of this study was to show how the computational intelligence techniques can be useful to predict the GSD by using different process conditions of roll compaction and material properties. Different techniques such as multiple linear regression, artificial neural networks, random forest, Cubist and k-nearest neighbors algorithm assisted by sevenfold cross-validation were used to present generalized models for the prediction of GSD based on roll compaction process setting and material properties. The normalized root-mean-squared error and the coefficient of determination (R2) were used for model assessment. The best fit was obtained by Cubist model (normalized root-mean-squared error =3.22%, R2=0.95). Based on the results, it was confirmed that the material properties (true density) followed by compaction force have the most significant effect on GSD.

MCC-mannitol mixtures after roll compaction/dry granulation: percolation thresholds for ribbon microhardness and granule size distribution.

In roll compaction, the specific compaction force, the gap width and the roll speed are the most important settings as they have a high impact in the products obtained. However the mechanical properties of the mixture being compacted are also critical. For this reason, a multilevel full factorial design including these parameters as factors plus three repetitions of the center point was performed for microcrystalline cellulose, mannitol and five binary mixtures (15, 30, 50, 70 and 85% MCC). These two reference excipients were chosen in order to investigate the plastic/brittle behavior of mixtures for the roll compaction process. These materials were roll compacted in a 3-W-Polygran® 250/50/3 (Gerteis) and the ribbons obtained were collected and milled into granules which were characterized regarding granule size distribution. After statistical evaluation, it was found that the most critical factors affecting the D10, D50, D90 and the fines fraction from the granules were the gap width and the specific compaction force, as well as the proportion of MCC together with its quadratic effect and the interaction between force and proportion of MCC. The microhardness of the ribbons from the center point as well as the D10, D50, D90 and the fines fraction from the granules produced at these same conditions were characterized. In all the cases, the proportion of MCC, i.e. the composition of the mixture, showed also an important effect on these properties measured. In this sense, the percolation theory was applied in order to study further the importance of the plastic/brittle ratio by calculating the percolation threshold or the limit over which the behavior of the system changes. This resulted in values of 34% for the HU (expression of microhardness), 27% and 28% for the D10 and fines, respectively (percolation of MCC) and 84% and 85% for the D50 and D90, respectively (percolation of mannitol).

NEOPLASM study: Real-life use of lacosamide in patients with brain tumor-related epilepsy.

BACKGROUND: The choice of antiepileptic drug (AED) therapy in patients with brain tumor-related epilepsy (BTRE) is complicated, and there are a lack of robust clinical trial data to date. METHODS: The NEOPLASM (Neuroncologic Patients treated with LAcoSaMide) study was a 6-month, multicenter, retrospective, observational study in patients with BTRE treated with lacosamide. Patients were started on lacosamide because of a lack of efficacy or adverse events (AEs) with prior AEDs or suitability versus other AEDs, according to clinical practice. The primary efficacy variable was the seizure-free rate at 6months. Safety variables included the proportion of patients with an AE and the proportion with an AE that led to discontinuation. RESULTS: Overall, 105 patients from 14 hospital centers were included in the analysis. Treatment with lacosamide for 6months resulted in a 30.8% seizure-free rate, and 66.3% of patients had a ≥50% seizure reduction (responders). In the subset of patients included because of a lack of efficacy with prior AEDs, seizure-free rates were 28.0%, and 66.7% of patients were responders. No statistically significant differences in efficacy were observed according to the mechanism of action or enzyme-inducing properties of concomitant AEDs. Adverse events were reported by 41.9% of patients at 6months, and 4.7% of them led to discontinuation. The most common AEs were somnolence/fatigue and dizziness. Notably, 57.1% of the patients who were switched to lacosamide because of AEs with their previous therapy did not report any AE at 6-month follow-up. CONCLUSIONS: In this open-label, observational study, lacosamide appeared to be effective and well tolerated in a large population of patients with BTRE. Lacosamide may therefore be a promising option for the treatment of patients with BTRE.

Effect of roll-compaction and milling conditions on granules and tablet properties.

Dry granulation is an agglomeration process used to produce size-enlarged particles (granules), improving the handling properties of powders such as flowability. In this process, powders are compacted using a roll press to produce ribbons, which are milled in granules used further in the tableting process. The granule and tablet properties are influenced by the existence of different designs of the roll compactors, milling systems and the interaction between process parameters and raw material properties. The main objective of this work was to investigate how different roll-compaction conditions and milling process parameters impact on ribbons, granules and tablet properties, highlighting the role of the sealing system (cheek plates and rimmed roll). In this context, two common excipients differing in their mechanical behaviour (MCC and mannitol) are used. The study is based on the analysis of granule size distribution together with the characterization of loss of compactability during die compaction. Results show that the tensile strength of tablets is lower when using granules than when the raw materials are compressed. Moreover, the plastic material (MCC) is more sensitive than the brittle one (mannitol). Regarding the roll-force, it is observed that the higher the roll force, the lower the tensile strength of tablets from granulated material is. These findings are in agreement with the literature. The comparison of sealing systems shows that the rimmed-roll system leads to slightly stronger tablets than the use of cheek plates. In addition, the use of the rimmed-roll system reduces the amount of fines, in particular when high roll force is applied. Overall, it can be concluded that roll-compaction effect is predominant over the milling effect on the production of fines but less significant on the tablet properties. This study points out that the balance between a good flowability by reducing the amount of fines and appropriate tablet strength is achieved with rimmed-roll and the highest roll-force used.

Robust and Accurate Modeling Approaches for Migraine Per-Patient Prediction from Ambulatory Data.

Migraine is one of the most wide-spread neurological disorders, and its medical treatment represents a high percentage of the costs of health systems. In some patients, characteristic symptoms that precede the headache appear. However, they are nonspecific, and their prediction horizon is unknown and pretty variable; hence, these symptoms are almost useless for prediction, and they are not useful to advance the intake of drugs to be effective and neutralize the pain. To solve this problem, this paper sets up a realistic monitoring scenario where hemodynamic variables from real patients are monitored in ambulatory conditions with a wireless body sensor network (WBSN). The acquired data are used to evaluate the predictive capabilities and robustness against noise and failures in sensors of several modeling approaches. The obtained results encourage the development of per-patient models based on state-space models (N4SID) that are capable of providing average forecast windows of 47 min and a low rate of false positives.

Polineuropatía periférica en un paciente con enfermedad pulmonar obstructiva crónica grave / Peripheral Polyneuropathy in a Patient With Severe Chronic Obstructive Pulmonary Disease

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The perception of facial aesthetics in a young Spanish population.

Improved facial aesthetics is one aim of orthodontic treatment. This study was designed to determine if the faces considered more beautiful in a young population exhibit the same parameters used by orthodontists to assess successful results. A panel of 34 laypeople (30 females and 4 males) evaluated a set containing one frontal, one frontal during smiling, and one profile photograph of 89 students (77 females and 12 males) on a 5-point attractiveness scale, in relation to a set of reference photographs. For each photographic set, the mean and final scores were calculated. Once the sample was established, 11 subjects (9 females and 2 males) with the highest final facial aesthetic score were selected and cephalometric analysis was performed. All cephalometric measurements were within the norm for the total sample. When the sample was divided by gender, Wilcoxon's W non-parametric test showed significant differences between the male and female photographs; while females tended to a Class II malocclusion, with the mandible slightly retrusive to the maxilla, males tended to a Class III and showed a straighter profile with a prominent chin; the face height ratio was higher in males. There were no significant differences between genders for lower lip to E plane. The findings show that the faces considered more attractive fulfilled the cephalometric and facial norms.

[Communication of needs in laryngectomized patients: Pictorrino]. / Comunicación de necesidades en el paciente laringectomizado: Pictorrino.

OBJECTIVE: To design, create and validate a pictogram, called Pictorrino, as a tool to obtain direct and simple communication with laryngectomized patients. PATIENTS AND METHODS: In a prospective sample of 10 laryngectomized patients within the first postoperative week, their principal needs and demands were evaluated, and were confirmed in a retrospective second sample of 10 laryngectomized patients who attended reviews in the outpatient clinic. Thereafter, pictograms were created to state such needs in as clear a fashion as possible. RESULTS: A pictogram was designed and validated, named and registered as Pictorrino, consisting of a board, which showed these pictograms on one of its sides, and a visual analogue scale of pain, with the aim of enabling the patient to express the demand or need at every moment. CONCLUSIONS: With Pictorrino we have achieved a multicultural tool that allows a more direct communication with laryngectomized patients.

Comunicación de necesidades en el paciente laringectomizado: Pictorrino© / Communication of needs in laryngectomized patients: Pictorrino©

Objetivo: Diseñar, elaborar y validar un pictograma, llamado Pictorrino©, como herramienta de comunicación directa y sencilla con el paciente laringectomizado. Pacientes y métodos: En una muestra prospectiva de 10 laringectomizados durante la primera semana posquirúrgica, se evaluaron las principales necesidades y demandas del paciente, que se confirmaron de forma retrospectiva con otra muestra de 10 pacientes laringectomizados que acudían a revisión en consultas. A continuación, se procedió a la elaboración de unos pictogramas que plasmaran lo más gráficamente posible dichas necesidades. Resultados: Se diseñó y validó un pictograma, denominado y registrado como Pictorrino©, consistente en una pizarra en la que en una de sus caras muestra dichos pictogramas y una escala visual analógica de dolor, con el fin de que el paciente señale la demanda o necesidad que presente en cada momento. Conclusiones: Con el Pictorrino© hemos conseguido una herramienta multicultural que nos permite una comunicación más directa con el paciente laringectomizado (AU)

Objective: To design, create and validate a pictogram, called Pictorrino©, as a tool to obtain direct and simple communication with laryngectomized patients. Patients and methods: In a prospective sample of 10 laryngectomized patients within the first postoperative week, their principal needs and demands were evaluated, and were confirmed in a retrospective second sample of 10 laryngectomized patients who attended reviews in the outpatient clinic. Thereafter, pictograms were created to state such needs in as clear a fashion as possible. Results: A pictogram was designed and validated, named and registered as Pictorrino©, consisting of a board, which showed these pictograms on one of its sides, and a visual analogue scale of pain, with the aim of enabling the patient to express the demand or need at every moment. Conclusions: With Pictorrino© we have achieved a multicultural tool that allows a more direct communication with laryngectomized patients (AU)

Uptake and depuration of anatoxin-a by the mussel Mytilus galloprovincialis (Lamarck, 1819) under laboratory conditions.

Cyanobacterial blooms tend to be more common in warm and nutrient-enriched waters and are increasing in many aquatic water bodies due to eutrophication. The aim of this work is to study the accumulation and depuration of anatoxin-a by Mytilus galloprovincialis a widespread distributed mussel living in estuarine and coastal waters and recognized worldwide as a bioindicator (e.g. Mussel Watch programs). Research on the distribution and biological effects of anatoxin-a in M. galloprovincialis is important. Nevertheless, the risk of human intoxication due to the consumption of contaminated bivalves should also be considered. A toxic bloom was simulated in an aquarium with 5 x 10(5) cell ml(-1) of Anabaena sp. (ANA 37), an anatoxin-a producing strain. Mussels were exposed to Anabaena for 15 days and then 15 days of depuration followed. Three or more animals were sampled every 24h for total toxin quantification and distribution in soft tissues (edible parts). Water samples were also taken every 24h in order to calculate total dissolved and particulate anatoxin-a concentrations. Anatoxin-a was quantified by HPLC with fluorescence detection. No deaths occurred during accumulation and depuration periods. One day after the beginning of depuration, the toxin could not be detected in the animals. Anatoxin-a is distributed in the digestive tract, muscles and foot and is probably actively detoxified.