Unique Polyhalogenated Peptides from the Marine Sponge Ircinia sp.

Two new bromopyrrole peptides, haloirciniamide A (1) and seribunamide A (2), have been isolated from an Indonesian marine sponge of the genus Ircinia collected in the Thousand Islands (Indonesia). The planar structure of both compounds was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of Marfey's method. Compound 1 is the first dibromopyrrole cyclopeptide having a chlorohistidine ring, while compound 2 is a rare peptide possessing a tribromopyrrole ring. Both compounds failed to show significant cytotoxicity against four human tumor cell lines, and neither compound was able to inhibit the enzyme topoisomerase I or impair the interaction between programmed cell death protein PD1 and its ligand, PDL1.

On-chip Heaters for Tension Tuning of Graphene Nanodrums.

For the study and application of graphene membranes, it is essential to have means to control their resonance frequency and temperature. Here, we present an on-chip heater platform for local tuning of in-plane tension in graphene mechanical resonators. By Joule heating of a metallic suspension ring we show thermomechanical resonance frequency tuning in a few-layer (FL) graphene nanodrum, which is accompanied by an increase in its quality factor, which we attribute to the increase of the in-plane tension. The in situ control of temperature, in-plane tension, resonance frequency, and quality factor of suspended two-dimensional (2D) nanodrums makes this device a unique platform for investigating the origin of dissipation in these ultrathin structures and can be of fundamental importance for studying the thermal properties of 2D materials. Moreover, by simultaneously controlling the heater and the backgate voltage, we can independently control the resonance frequency and quality factor, which is of great importance for applications in sensors and resonant mechanical filters.

Graphene Squeeze-Film Pressure Sensors.

The operating principle of squeeze-film pressure sensors is based on the pressure dependence of a membrane's resonance frequency, caused by the compression of the surrounding gas which changes the resonator stiffness. To realize such sensors, not only strong and flexible membranes are required, but also minimization of the membrane's mass is essential to maximize responsivity. Here, we demonstrate the use of a few-layer graphene membrane as a squeeze-film pressure sensor. A clear pressure dependence of the membrane's resonant frequency is observed, with a frequency shift of 4 MHz between 8 and 1000 mbar. The sensor shows a reproducible response and no hysteresis. The measured responsivity of the device is 9000 Hz/mbar, which is a factor 45 higher than state-of-the-art MEMS-based squeeze-film pressure sensors while using a 25 times smaller membrane area.

Colorimetry Technique for Scalable Characterization of Suspended Graphene.

Previous statistical studies on the mechanical properties of chemical-vapor-deposited (CVD) suspended graphene membranes have been performed by means of measuring individual devices or with techniques that affect the material. Here, we present a colorimetry technique as a parallel, noninvasive, and affordable way of characterizing suspended graphene devices. We exploit Newton's rings interference patterns to study the deformation of a double-layer graphene drum 13.2 µm in diameter when a pressure step is applied. By studying the time evolution of the deformation, we find that filling the drum cavity with air is 2-5 times slower than when it is purged.

Visualizing the Motion of Graphene Nanodrums.

Membranes of suspended two-dimensional materials show a large variability in mechanical properties, in part due to static and dynamic wrinkles. As a consequence, experiments typically show a multitude of nanomechanical resonance peaks, which make an unambiguous identification of the vibrational modes difficult. Here, we probe the motion of graphene nanodrum resonators with spatial resolution using a phase-sensitive interferometer. By simultaneously visualizing the local phase and amplitude of the driven motion, we show that unexplained spectral features represent split degenerate modes. When taking these into account, the resonance frequencies up to the eighth vibrational mode agree with theory. The corresponding displacement profiles, however, are remarkably different from theory, as small imperfections increasingly deform the nodal lines for the higher modes. The Brownian motion, which is used to calibrate the local displacement, exhibits a similar mode pattern. The experiments clarify the complicated dynamic behavior of suspended two-dimensional materials, which is crucial for reproducible fabrication and applications.

Histomorphometric results in ridge preservation procedures comparing various graft materials in extraction sockets with nongrafted sockets in humans: a systematic review.

INTRODUCTION: The aim of this systematic review was to evaluate, from a histological point of view, the amount of newly formed bone in ridge preservation procedures using various graft materials in comparison with natural healing (NH) and to determine which is the ideal type of graft to be used. MATERIALS AND METHODS: A search strategy was developed to find articles in a human model published between 1990 and January 2013 in English language using MEDLINE database. RESULTS: Thirty-four articles were included in this systematic review. When comparing the percentage of newly formed bone using various grafting materials with NH, calcium sulfate, magnesium enriched hydroxyapatite, and porcine-derived bone grafts offered the best outcomes. However, due to the heterogeneity of the included studies, the search was extended to determine which type of graft resulted in greatest bone formation. CONCLUSION: When comparing ridge preservation with NH, only 3 studies encountered a greater amount of newly formed bone in the ridge preservation group, whereas the rest did not find statistically significant differences or even observed a greater percentage of newly formed bone in the control group. Therefore, more studies are needed to determine whether the use of graft materials enhances new bone formation in contrast to NH alone and to determine the most effective bone grafting material.

Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds.

Microtubules continue to be one of the most successful anticancer drug targets and a favorite hit for many naturally occurring molecules. While two of the most successful representative agents in clinical use, the taxanes and the vinca alkaloids, come from terrestrial sources, the sea has also proven to be a rich source of new tubulin-binding molecules. We describe herein the first isolation, structural elucidation and total synthesis of two totally new polyketides isolated from the Madagascan sponge Lithoplocamia lithistoides . Both PM050489 and PM060184 show antimitotic properties in human tumor cells lines at subnanomolar concentrations and display a distinct inhibition mechanism on microtubules. The development of an efficient synthetic procedure has solved the supply problem and, following pharmaceutical development, has allowed PM060184 to start clinical studies as a promising new drug for cancer treatment.

Stolonoxides E and F, cytotoxic metabolites from the marine ascidian Stolonica socialis.

Two new members of the stolonoxide family, stolonoxides E (1) and F (2), were isolated from samples of the marine ascidian Stolonica socialis collected in Cádiz (Spain). Their structures were determined by a combination of techniques, including (+)-HRESIMS, 1D and 2D NMR spectroscopy, and comparison with published data for the structurally related stolonoxides A-D (3-6). Both compounds displayed cytotoxicity against a panel of three human tumor cell lines.

Diabetes mellitus and work. Assessment and questionnaires revision. / Diabetes mellitus y trabajo. Valoración y revisión de cuestionarios.

Diabetes mellitus presents high prevalence, severe complications, clinical repercussions, costs and occupational implications. Their assessment requires the use of the medical history and support questionnaires. A literature review was conducted on the topic of clinical and occupational evaluation aspects of diabetes; the database searched was Medline. The search showed numerous papers about diabetes clinical and therapeutic aspects as well as social or public health aspects but the results lacked occupational aspects. To assess the disease, the use of questionnaires is generalized and each author selects those which fit best to their purpose. It is concluded that to carry out a clinical and occupational evaluation related to diabetes, an inter-specialities cooperation, based on a complete medical history including occupational risk factors, is recommended. The questionnaires are useful, adapted to the objective, recommending those valued in Spanish as in Fear of hypoglycemia questionnaire (EsHFS) and Diabetes-related quality of life questionnaire (EsDQOL).

Cytotoxic staurosporines from the marine ascidian Cystodytes solitus.

Two new indolocarbazole alkaloids, 7-oxo-3,8,9-trihydroxystaurosporine (1) and 7-oxo-8,9-dihydroxy-4'-N-demethylstaurosporine (2), were isolated from samples of the marine ascidian Cystodytes solitus. Their structures were determined by a combination of spectroscopic techniques, including (+)-HRMALDITOFMS and 1D and 2D NMR spectroscopy, and comparison with published data for related structures. Both compounds displayed strong cytotoxicity against three human tumor cell lines.

[Ethical and legal implications of biomedical research]. / Implicaciones éticas y legales de la investigación biomédica.

The major advances in biomedical research pose ethical and legal problems for the researchers, institutions and companies responsible for these advances. This new vision of their professional task results from the necessary protection of patients' rights and responsibilities, reflected in international documents and specific legislation in distinct countries, which are globally being adopted by transnational research, linked -in turn- to translational research. The pluridisciplinary nature of current biomedical research is reflected in the field of the rights and responsibilities to be protected. Thus, Ethics, Bioethics and the Law started an ineludible and intense dialogue that has even given rise to new areas of knowledge such as Healthcare Law and Biolaw. Personalized medicine constitutes a new healthcare criterion while pharmacogenetics may be a good study model, able to promote deliberation and prudence in decisions. Finally, Health Economics is essential, not only to benefit from its technical experience but also to rediscover the ethics that gave rise to this discipline.

Papilla and pontic area regeneration in patient with gingival smile: A clinical case.

PURPOSE: Connective tissue grafts are widely documented as a predictable technique for treating Miller Class I and II recessions, as well as procedures in which soft tissue augmentation is required for aesthetic reasons. This article aims to explore the resolution of a clinical case with this type of problema. CLINICAL CASE: This case describes a technique for reconstructing a pontic area and adjacent papilla by means of two consecutive connective tissue grafts. The first graft served to increase the amount of tissue in the horizontal direction, and the second promoted vertical reconstruction of the defect. RESULTS AND CONCLUSION: In cases with aesthetic requirements, restorative intervention may be able to mask tissue loss, but it can hardly achieve optimal aesthetic results. Periodontal plastic surgery techniques can be used to achieve that ideal result. The clinician must diagnose conditions in order to select correct treatment regimen for each individual case. Key words:Papilla, gingival smile, pontic, restorative dentistry.

Graphene mechanical pixels for Interferometric Modulator Displays.

Electro-optic modulators based on micro-electromechanical systems have found success as elements for optical projectors, for simplified optical spectrometers, and as reflective-type screens that make use of light interference (Interferometric Modulator Display technology). The latter concept offers an exciting avenue for graphene nanomechanical structures to replace classical micro-electromechanical devices and bring about enhancement in performance, especially switching speed and voltage. In this work we study the optical response of electrically actuated graphene drumheads by means of spectrometric and stroboscopic experiments. The color reproducibility and speed of these membranes in producing the desired electro-optic modulation makes them suitable as pixels for high refresh rate displays. As a proof of concept, we demonstrate a Graphene Interferometric Modulator Display prototype with 5 µm-in-diameter pixels that compose a high resolution image (2500 pixels per inch)-equivalent to a 5″ display of 12K-whose color can be changed at frame rates of at least 400 Hz.

Mandibular ameloblastoma. Reconstruction with iliac crest graft and implants.

The ameloblastoma is a bening odontogenic tumor. The treatment planning in young persons is still not clear. We describe a case report of a young boy who was treated in our unit and we review the different approaches for this type of lesions, which nowadays still not clear in this patients.

Very large scale characterization of graphene mechanical devices using a colorimetry technique.

We use a scalable optical technique to characterize more than 21 000 circular nanomechanical devices made of suspended single- and double-layer graphene on cavities with different diameters (D) and depths (g). To maximize the contrast between suspended and broken membranes we used a model for selecting the optimal color filter. The method enables parallel and automatized image processing for yield statistics. We find the survival probability to be correlated with a structural mechanics scaling parameter given by D4/g3. Moreover, we extract a median adhesion energy of Γ = 0.9 J m-2 between the membrane and the native SiO2 at the bottom of the cavities.

Exome Sequencing and Clot Lysis Experiments Demonstrate the R458C Mutation of the Alpha Chain of Fibrinogen to be Associated with Impaired Fibrinolysis in a Family with Thrombophilia.

AIM: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. METHODS: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clot lysis experiments were performed to analyze the reasons of the altered fibrinolytic activity caused by the mutation found. RESULTS: We found a mutation that consists of a R458C substitution on the fibrinogen alpha chain (FGA) gene confirmed in 13 new familial subjects that causes a rare subtype of dysfibrinogenemia characterized by venous thromboembolic events. The mutation was already reported to be associated with a fibrinogen variant called fibrinogen Bordeaux. Clot-lysis experiments showed a decreased and slower fibrinolytic activity in carriers of this mutation as compared to normal subjects, thus demonstrating an impaired fibrinolysis of fibrinogen Bordeaux. CONCLUSIONS: The exome sequencing and clot-lysis experiments might be powerful tools to diagnose idiopathic thrombophilias after an unsuccessful set of biochemical laboratory tests. Fibrinogen Bordeaux is associated with impaired fibrinolysis in this family with idiopathic thrombophilia.

Valoración de limitaciones en reumatología. Herramientas más utilizadas en la práctica / Assessment of limitations in rheumatology. Tools most used in practice

Resumen Introducción: Las enfermedades reumáticas son patologías de alta prevalencia, impacto y repercusión, caracterizadas por dolor y limitación funcional. Para valorar la limitación, la historia clínica es el punto de partida, junto con las pruebas específicas necesarias, según el tipo de padecimiento. De forma complementaria, se recomienda el uso de herramientas clinimétricas. Objetivo: Comparar algunas herramientas o cuestionarios usados en las enfermedades reumáticas más prevalentes, revisando la bibliografía para destacar sus aportes y su utilidad en la labor del médico con finalidad clínica o pericial. Método: Se revisan las características básicas de los cuestionarios y herramientas más usadas en: osteoartritis, artritis reumatoide y artritis psoriásica, espondilitis anquilosante y lupus eritematoso sistémico. Se revisa en Medline la experiencia de los autores con algunos cuestionarios en función de la patología y de sus diversos usos. Resultados: Los cuestionarios se utilizan en su mayoría para la valoración de la calidad de vida, la discapacidad y la evolución clínico-terapéutica de los pacientes. No hay acuerdo entre los autores sobre si existe prioridad en el uso de algún cuestionario concreto por patología y se tiende a combinar varios. Los cuestionarios genéricos más utilizados son SF-36, NHP y EQ-5D. Por enfermedades: en artritis reumatoide, HAQy DAS28; en osteoartritis, WOMAC y Knoos; en Lupus, SLEDAI y BICLA, y en espondilitis, BASDAI y ASDAS. Conclusiones: En reumatología los cuestionarios son de uso habitual y resultan de utilidad de forma complementaria a la historia clínica y a las pruebas específicas. La elección por el profesional médico se basa en su experiencia y en la adecuación al objetivo buscado.

Abstract Introduction: Rheumatic diseases are high prevalence, high impact and repercussion pathologies characterised by pain and functional limitation. To assess the limitation, the starting point is the clinical history, together with the specific tests required according to the type of condition. The use of complimentary clinometric tools is recommended. Objective: To compare some tools or questionnaires used in the most prevalent rheumatic diseases, and a review of the literature to highlight their contributions and usefulness in medical practice by the clinician or expert. Method: A review is made of the basic characteristics of the questionnaires and the most used tools in osteoarthritis, rheumatoid arthritis and psoriatic arthritis, ankylosing spondylitis and systemic lupus erythematosus. The experience of the authors is reviewed in Medline, with some questionnaires depending on the pathology and its various uses. Results: The questionnaires are used mainly to assess the quality of life, disability, and clinical-therapeutic evolution of patients. There is no agreement among the authors on whether there is a priority in the use of a specific questionnaire by pathology, and there is a tendency to combine several. The most commonly used generic questionnaires are SF-36, NHP and EQ-5D. For diseases: in rheumatoid arthritis, the HAQ and DAS28; in osteoarthritis, WOMAC and Knoos; in lupus, SLEDAI and BICLA; and in spondylitis, BASDAI and ASDAS. Conclusions: In rheumatology, questionnaires are commonly used, and are useful as a complement to the clinical history and specific tests. The choice by the medical professional is based on their experience and on the adaptation to the objective sought.

Cuestionarios de valoración funcional en traumatología / Trauma functional assessment questionnaires

RESUMEN Introducción: Las enfermedades musculoesqueléticas son dolencias de alta prevalencia, impacto y repercusión. La historia clínica y las pruebas complementarias son las primeras pautas para diagnosticarlas. Se recomienda el uso de cuestionarios para la valoración de las limitaciones e impacto en la calidad de vida de los pacientes. Objetivo: Valorar el uso y eficacia de los cuestionarios en traumatología. Métodos: Se revisaron las bases de datos Medline, Pubmed. Se obtuvieron 32 publicaciones, fundamentalmente, en inglés, aunque también en español y otros idiomas, realizadas entre 2001-2018, que recogen la experiencia de los investigadores con el uso de los cuestionarios. Los términos de búsqueda empleados fueron: Musculoskeletal Disorders, Musculoskeletal pain; and Foot and Ankle, hip and knee, Upper Extremity, low back pain; and disability, quality of life questionnaires and assessment tool. Resultados: Se han revisado 46 cuestionarios: 4 de calidad de vida, 16 de miembro superior (1 general y 15 por localización de la lesión), 19 de miembro inferior (4 generales y 15 por localización de la lesión) y 7 para raquis. Conclusiones: No hay acuerdo en los autores sobre cuál es el mejor cuestionario para la valoración de impacto y repercusión, y se combinan varios de ellos. La elección del cuestionario y el que sea genérico (de calidad de vida) o específico (de miembro superior, inferior o raquis), está en consonancia con el objetivo buscado en la investigación, la experiencia del investigador, su uso clínico y tiempo necesario para cumplimentarlo(AU)

ABSTRACT Introduction: Musculoskeletal diseases are ailments of high prevalence, impact and impact. The medical record and the complementary tests are the first guidelines to diagnose them. The use of questionnaires is recommended to assess the limitations and impact on the quality of life of patients. Objective: To assess the use and effectiveness of traumatology questionnaires. Methods: Medline, Pubmed databases were reviewed. We recovered 32 publications mainly in English, but also in Spanish and other languages, made from 2001 to 2018. These publications collect the experience of researchers with the use of questionnaires. The search terms used were Musculoskeletal Disorders, Musculoskeletal pain; and Foot and Ankle, hip and knee, Upper Extremity, low back pain; and disability, quality of life questionnaires and assessment tool. Results: Forty six questionnaires were reviewed. Four on quality of life, 16 on the upper limbs (one general and 15 by location of the lesion), 19 on the lower limbs (four general and 15 by location of the lesion) and 7 on spine. Conclusions: There is no consensus among the authors on which is the best questionnaire for assessing of the impact and repercussion. Several of them are combined. The choice of the questionnaire and the one that is generic (on quality of life) or specific (on upper, lower limbs or spinal) is in line with the objective sought in this research, the researcher´s experience, clinical use and the time needed to fill it out(AU)

RÉSUMÉ Introduction: Les troubles musculo-squelettiques sont des affections dont la prévalence, l'impact et le retentissement sont élevés. Le dossier médical et les examens complémentaires sont les premières orientations pour les diagnostiquer. L'emploi des questionnaires pour évaluer les limitations et l'impact sur la qualité de vie des patients est recommandé. Objectif: Évaluer l'emploi et l'efficacité des questionnaires en traumatologie. Méthodes: On a consulté les bases de données Medline et PubMed. On a obtenu 32 publications notamment en anglais, mais aussi en espagnol et d'autres langues, parues entre 2001-2018, recueillant toute l'expérience des chercheurs dans l'usage des questionnaires. Les termes de recherche utilisés ont été: Musculoskeletal Disorders, Musculoskeletal pain ; and Foot and Ankle, hip and knee, Upper Extremity, low back pain ; and disability, quality of life questionnaires and assessment tool. Résultats: Sur 46 questionnaires, on a révisé 4 concernant la qualité de vie, 16 concernant les membres supérieurs (1 de sujet général et 15 de localisation de la lésion), 19 concernant les membres inférieurs (4 de sujet général et 15 de localisation de la lésion), et 7 concernant le rachis. Conclusions: Les auteurs ne sont pas arrivés à un consensus sur le meilleur questionnaire pour évaluer l'impact et le retentissement; on a fait une combinaison de plusieurs d'entre eux. La sélection d'un questionnaire et le fait qu'il soit générique (qualité de vie) ou spécifique (membre supérieur, inférieur ou rachis) ont été en concordance avec l'objectif de la recherche, l'expérience du chercheur, l'usage clinique et le temps nécessaire pour le compléter(AU)

La Fibromialgia en la jurisprudencia Española. Herramienta FMCheck de Valoración / Fibromyalgia in de Spanish caselaw. FM-Check Assessment Tool

La fibromialgia se define como un estado doloroso generalizado que no afecta a las articulaciones, sino a zonas musculares y raquis con una exagerada sensibilidad a la presión en unos puntos determinados, así lo recoge la Organización Mundial de la Salud desde 1992, incluyéndola en el CIE-10 con el código M79.0.Especialmente compleja es la valoración de sus limitaciones desde el punto de vista clínico, social, laboral o pericial. Esta complejidad trasciende al ámbito médico-legal y se refleja en las cuantiosas sentencias recogidas (más de 30.000), de las que el 96% se corresponden con el área de lo Social y en los conceptos de Limitación e Incapacidad laboral. La herramienta FM-Check puede servir de apoyo para una valoración homogénea, integral y objetiva, evitando inequidades. Puede complementarse con otras en función del destino de la valoración y calificación al que se encamine al paciente/trabajador afectado..(AU)

Fibromyalgia was defined in 1992 by the World Health Organization as a general painful state that does not affect the joints, but muscle areas and rachis with an exaggerated sensitivity to pressure at specific points and was included in the ICD-10 with M79.0 code. Especially complex is the valuation of its limitations both in terms of clinical, social,occupational, or expert view. This complexity transcends the forensic field and is reflected in the substantial sentences collected (over 30,000), of which 96% correspond to the area of the Social and concepts of limitation and disability. The FM-Check tool can support for seamless, omprehensive and objective assessment,avoiding inequities. It can be complemented with other depending on the destination of the assessment and qualification to which the patient / affected worker is heading..(AU)

A novel surgical procedure for coronally repositioning of the buccal implant mucosa using acellular dermal matrix: a case report.

BACKGROUND: This case report describes a surgical procedure for coronally advancing the peri-implant mucosa to treat a soft tissue dehiscence in a single-tooth implant-supported restoration in combination with an acellular dermal matrix graft. METHODS: The patient was a 41-year-old systemically healthy, non-smoking female. Her chief complaint pertained to the unesthetic appearance of her right lateral upper incisor, caused by recession of the mucosal margin. On examination, a 3-mm recession could be observed. The periodontium was classified as thin. A 2-mm band of keratinized peri-implant mucosa was present. Keratinized gingiva was approximately 6 mm at adjacent areas. The surgical technique included a novel incision design to coronally position the flap over an acellular dermal matrix graft. RESULTS: Partial coverage of the recession was achieved. After a 6-month period, tissues appeared thicker than preoperatively, with no bleeding on probing and no probing depth >2 mm. The patient was satisfied with the overall treatment result. CONCLUSIONS: This case report shows the possibility of achieving partial soft tissue coverage over an implant-supported restoration with the combined use of an acellular dermal matrix and a coronally positioned flap. A novel technique is presented that allowed advancing the flap over the graft in a single-tooth restoration where enough keratinized tissue was present preoperatively.