Search

Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient’s response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.

Blue sharks

Among other circumstances relevant to maritime delimitations, some States have recently used the protection of underwater cultural heritage (UCH) as grounds for advancing jurisdictional or sovereignty claims over different maritime areas. After identifying the contours of current international law governing that heritage, this book critically addresses: first, the generally limited use of archaeological heritage in territorial claims; second, the broad acceptance by States of ‘archaeological maritime zones’ that overlap with declared contiguous zones; and, third, the (mis)use of UCH and underwater archaeology in three still disputed maritime claims, namely, Canada’s claim in Arctic waters, China’s in the South China Sea, and Russia’s in Crimea and its surrounding waters. Legal and ethical issues related to underwater archaeology are also discussed.

Each individual cetacean is an ecosystem itself, potentially harboring a great variety of animals that travel with it. Despite being often despised or overlooked, many of these epizoites have been proven to be suitable bio-indicators of their cetacean hosts, informing on health status, social interactions, migration patterns, population structure or phylogeography. Moreover, epizoites are advantageous over internal parasites in that many of them can be detected by direct observation (e.g., boat surveys), thus no capture or dissection of cetaceans are necessary. Previous reviews of epizoites of cetaceans have focused on specific geographical areas, cetacean species or epibiotic taxa, but fall short to include the increasing number of records and scientific findings about these animals. Here we present an updated review of all records of associations between cetaceans and their epibiotic fauna (i.e., commensals, ecto- or mesoparasites, and mutualists). We gathered nearly 500 publications and found a total of 58 facultative or obligate epibiotic taxa from 11 orders of arthropods, vertebrates, cnidarians, and a nematode that are associated to the external surface of 66 cetacean species around the globe. We also provide information on the use as an indicator species in the literature, if any, and about other relevant traits, such as geographic range, host specificity, genetic data, and life-cycle. We encourage researchers, not only to provide quantitative data (i.e., prevalence, abundance) on the epizoites they find on cetaceans, but also to inform on their absence. The inferences drawn from epizoites can greatly benefit conservation plans of both cetaceans and their epizoites.

Antarctic minke whales,Balaenoptera bonaerensis, breed in tropical and temperate waters of the Southern Hemisphere in winter and feed in Antarctic grounds in the austral summer. These seasonal migrations could be less defined than those of other whale species, but the evidence is scanty. We quantitatively describe the epibiotic fauna of Antarctic minke whales and explore its potential to trace migrations. Seven species were found on 125 out of 333 examined Antarctic minke whales captured during the last Antarctic NEWREP-A expedition in the Southern Ocean: the amphipodBalaenocyamus balaenopterae(prevalence = 22.2%), the copepodPennella balaenoptera(0.6%); three coronulid, obligate barnacles,Xenobalanus globicipitis(11.1%),Coronula reginae(8.7%),C. diadema(0.9%); and two lepadid, facultative barnacles,Conchoderma auritum(9.0%) andC. virgatum(0.3%). Species with prevalence > 8% exhibited a modest increase in their probability of occurrence with whale body length. Data indicated positive associations between coronulid barnacles and no apparent recruitment in Antarctic waters.All specimens ofX. globicipitiswere dead, showing progressive degradation throughout the sampling period, and a geographic analysis indicated a marked drop of occurrence where the minimum sea surface temperature is X. globicipitis, on whales in the Southern Ocean could evince seasonal migration. Future investigations on geographical distribution, growth rate, and degradation (forX. globicipitis) could also assist in timing whales’ migration.

Brewers spent grain (BSG) is the largest by-product originated from the brewery industry with a high potential for producing carbohydrases by solid-state fermentation. This work aimed to test the efficacy of a carbohydrases-rich extract produced from solid-state fermentation of BSG, to enhance the digestibility of a plant-based diet for European seabass (Dicentrarchus labrax). First, BSG was fermented with A. ibericus to obtain an aqueous lyophilized extract (SSF-BSG extract) and incorporated in a plant-based diet at increasing levels (0control; 0.1%, 0.2%, and 0.4%). Another diet incorporating a commercial carbohydrases-complex (0.04%; Natugrain; BASF) was formulated. Then, all diets were tested in in vitro and in vivo digestibility assays. In vitro assays, simulating stomach and intestine digestion in European seabass, assessed dietary phosphorus, phytate phosphorus, carbohydrates, and protein hydrolysis, as well as interactive effects between fish enzymes and dietary SSF-BSG extract. After, an in vivo assay was carried out with European seabass juveniles fed selected diets (0control; 0.1%, and 0.4%). In vitro digestibility assays showed that pentoses release increased 45% with 0.4% SSF-BSG extract and 25% with Natugrain supplemented diets, while amino acids release was not affected. A negative interaction between endogenous fish enzymes and SSF-BSG extract was observed in both diets. The in vivo digestibility assay corroborated in vitro data. Accordingly, the dietary supplementation with 0.4% SSF-BSG increased the digestibility of dry matter, starch, cellulose, glucans, and energy and did not affect protein digestibility. The present work showed the high potential of BSG to produce an added-value functional supplement with high carbohydrases activity and its potential contribution to the circular economy by improving the nutritional value of low-cost and sustainable ingredients that can be included in aquafeeds. © 2021, The Author(s)., Te authors thank UNICER, a sof-drink company (Porto, Portugal), for providing the brewer’s spent grain used in this study. Tis study was supported by the project “SPO3-Development of innovative sustainable protein and omega-3 rich feedstufs for aquafeeds, from local agro-industrial by-products”, reference POCI-01- 0145-FEDER-030377, funded by European Regional Development Fund (ERDF) and Portuguese Foundation for Science and Technology (FCT) and by strategic funding of UIDB/04423/2020 by UIDB/04469/2020 unit, the BioTecNorte operation (NORTE-01-0145-FEDER-000004) through national funds provided by FCT, and under the scope of the strategic funding of UIDB/04469/2020 unit. Te H.F. and C.C were supported by grants SFRH/BD/131219/2017 and SFRH/BPD/114942/2016, respectively, from FCT, MCTES, FSE, and UE under the North Portugal Regional Operational Programme (NORTE2020). José Manuel Salgado was supported by Beatriz Galindo contract of Ministry of Education (Spain)., info:eu-repo/semantics/publishedVersion

Issue/problem Leptospirosis is an endemic disease which is mandatorily notifiable in Spain. It is associated with occupational activities in which workers come into contact with rat urine. In our region, this disease's rates of prevalence and incidence are highest among red swamp crayfish collectors (Procambarus clarkii) (RSCC). The increase in outbreaks of leptospirosis over the last 7 years has motivated us to design and implement a Clinical Practice Guide (CPG) for health workers, informational material for the general population, and ID cards and specific information aimed at RSCCs, as a means of reducing the incidence rate. The guide may also serve as a useful tool in other regions and countries with activities associated with Leptospira-infected wetlands. Description of the problem The material we have designed is the result of a research project funded by the Consejería de Salud de Andalucía to identify leptospirosis incidence, prevalence, and risk factors among wetland RSCCs. Hardly any CPGs or informational material exist about this disease. The GPC and the educational material designed may be very useful in other environments with a high risk of leptospirosis. Results Prevalence of the disease was higher among RSCCs than among the general population (9.8% vs 3.1%) (OR: 3.4; CI 95%: 1.1-12.7) and accumulated incidence was 17.4%. Less than half of the workers adopted appropriate individual preventive measures. Lessons The risk of contracting leptospirosis is 3.4 times greater for the RSCC population than it is for the general population. Early detection and antibiotic therapy prevent aggravation of the disease in serious cases and may even prevent deaths. Education and the promotion of preventive measures among RSCCs reduces the risk of infection. The training of health professionals and the design of decision algorithms shorten and improve the quality of treatment for leptospirosis patients. Key messages Early detection and antibiotic therapy reduce the incidence of severe forms of leptospirosis. The material designed will help the risk population to adopt preventive measures and seek medical attention.

Spain has just declared a new marine protected area in the Mediterranean. This follows a protective trend taken by Spanish authorities during the last decades and has permitted Spain to honour its international compromises under the Convention on Biological Diversity. It contributes to a framework of protected areas established under conventional regimes such as OSPAR, RAMSAR or EU Natura 2000. The new area protects a ‘cetacean corridor’ and will be inscribed in the list of Specially Protected Areas of Mediterranean Importance under the Barcelona Convention regional framework.

In the standard AK growth model we introduce the threat of an ecological catastrophe and study the consequences for the economic variables in the long-run. We extend the basic framework by considering two environmental externalities: the first one is local and gives account of the marginal damage from emissions flow; the second one is aggregate, or global, and relates to the extreme damage which may happen if the accumulated stock of pollutants is on the threshold of a worldwide catastrophe. In this context dominated by market failures, we focus on the socially optimal solution and the search of conditions for sustainability. We identify the efficient balanced growth path, which may even show a singularity with trajectories truncating and changing course. In short, with respect to the economy’s long-run performance, we study how environment matters in different ways and at different stages, giving conditions to prevent the catastrophe and preserve (a lower) sustained growth. This paper may also be read as a clear and rigorous example of an optimal control problem involving a pure state-space constraint.

Background:Axial involvement in patients diagnosed of Psoriatic arthritis (PsA) in variable in previous studies. Axial involvement (according GRAPPA criteria) is based upon inflammatory spinal symptoms pain with loss of lumbar mobility and the presence of radiological sacroiliitis and other radiographic signs of spondylitis in patients with PsA.Objectives:Evaluate the prevalence of axial involvement in PsA an their clinical features.Methods:All patients included in the monographic PsA consultation database of our second level hospital were analyzed. Demographic, clinical and analytical variables were collected. Statistical analysis was performed using SPPSS v.25Results:We included 145 patients with PsA (fulfilling CASPAR criteria) with a mean age at diagnosis of 45,4 (±13) years and time of evolution of the disease 9,3 (±6,2) years. The proportion of the affectation types were: peripheral 94 (64,8%), mixta 31 (21,4%) and axial 20 (13,8%). Therefore, 51 (35,2%) patients meet criteria for axial involvement, of with 31 (21,4%) also had associated peripheral involvement. Table 1 shows the differences between patients with and without axial disease. Axial involvement was higher in males than women [OR=2,3 (1,1-4,7), p=0,023]. HLAB27, determined in 106 patients, was more prevalent in axial PsA than in exclusive peripheral patients, 35% and 4,5% respectively [OR=11,3 (3,0-42,7), p25) less frequently than peripheral disease [OR=0,4 (0,2-0,8), p=0,01)]. We didn’t find any differences in other comorbidities (arterial hypertension, diabetes, hyperlipemia, hyperuricemia, ischemic heart disease, depression) between patines with axial or peripheral disease.TABLE 1.Differences between axial and peripheral patternsWith axial involvement, n=51Without axial involvement, n=94OR (IC 95%)p valueAge at diagnosis, years (SD)44,6 (±13,3)45,9 (±12,8)0,6Time of evolution, years (SD)10 (±6,8)8,9 (±5,8)0,3Men, n (%)36 (42,9%)48 (57,1%)2,3 (1,1-4,7)0,02HLAB27, n (%)14 (82,4%)3 (17,6%)11,3 (3,0-42,7)Skin Psoriasis, n (%)47 (36,4%)82 (63,6%)1,7 (0,5-5,6)0,4Onicopathy, n (%)11 (26,2%)31 (73,8%)0,6 (0,2-1,2)0,1Dactilytis, n (%)9 (32,1%)19 (67,9%)0,8 (0,3-2,0)0,7Enthesitis, n (%)13 (44,8%)16 (55,2%)1,7 (0,7-3,8)0,2Uveitis, n (%)2 (66,7%)1 (33,3%)3,8 (0,3-42,9)0,2Inflammatory bowel disease, n (%)2 (66,7%)1 (33,3%)3,8 (0,3-42,9)0,2Hyperlipemia, n (%)27 (31%)60 (69%)0,6 (0,3-1,3)0,2BMI >25, n (%)22 (26,5%)61 (73,5%)0,4 (0,2-0,8)0,01Hypertension, n (%)18 (39,1%)28 (60,9%)1,3 (0,6-2,6)0,5Hyperuricemia, n (%)16 (39%)25 (61%)1,3 (0,6-2,7)0,5Smokers, n (%)13 (50%)13 (50%)2,1 (0,9-5,0)0,08Ischemic heart disease, n (%)8 (53,3%)7 (46,7%)2,3 (0,8-6,8)0,1Depression, n (%)7 (30,4%)16 (69,6%)0,8 (0,3-2,0)0,6Diabetes, n (%)7 (30,4%)20 (74,1%)0,6 (0,2-1,5)0,3Conclusion:Prevalence of axial involvement in our cohort (35,2%) is found within the data reported in other studies (25-70%). Nevertheless, we found less prevalence of HLAB27 positive than other reports. Patients with HLAB27 positive, dactylitis or uveitis are diagnosed at earlier ages.Disclosure of Interests:None declared

Species of Anisakis typically infect the stomach of cetaceans worldwide, often causing ulcerative lesions that may compromise the host's health. These nematodes also cause anisakiasis or allergic reactions in humans. To assess the risks of this emerging zoonosis, data on long-term changes in Anisakis infections in cetaceans are necessary. Here, we compare the prevalence and severity of ulcerative lesions caused by Anisakis spp. in five cetacean species stranded along the north-west Spanish coast in 2017-2018 with published data from 1991-1996. Open ulcers were found in 32/43 short-beaked common dolphins, Delphinus delphis; 3/5 striped dolphins, Stenella coeruleoalba; 1/7 bottlenose dolphins, Tursiops truncatus; and 1/3 harbour porpoises, Phocoena phocoena meridionalis; a single individual of long-finned pilot whale, Globicephala melas, was found uninfected. In common dolphins, the mean abundance of open ulcers per host was 1.1 (95% confidence interval: 0.8-1.3), with a maximum diameter (mean ± standard deviation) of 25.4 ± 16.9 mm. Stomachs with scars or extensive fibrosis putatively associated with Anisakis were detected in 14 and five animals, respectively. A molecular analysis based on the mitochondrial cytochrome c oxidase II gene using 18 worms from three cetacean species revealed single or mixed infections of Anisakis simplex sensu stricto and Anisakis pegreffii. Compared with the period 1991-1996, we found a strong increase of prevalence, abundance and extension of ulcerative lesions in most cetacean species. Anisakis populations could have increased in the study area over the last decades, although we cannot rule out that a higher environmental stress has also boosted the pathological effects of these parasites.

Remotely Piloted Aircraft System (RPAS) is a capital issue for the majority of aviation actors nowadays. The integration of RPAS is an extremely demanding task that must be tackled by multiple standpoints: economic, social, technological or environmental among others. U-space is the answer from Europe to design the operation of multiple and different types of RPAS. U-space is a set of novel services designed to support efficient, safe and secure access to airspace, from the very low level to the upper airspace. This paper focuses on the terminal airspace to design the operational concept for the integration of RPAS in conjunction with conventional aircraft and general aviation. This work develops a holistic methodology to analyse the way RPAS integration affect crucial factors and tries to bring to the light different issues that can frustrate their integration. First, we focus on detailing the requirements specified by RPAS legislation. Second, all the requirements are gathered into different categories to perform further analysis. The categorisation identifies navigation, communication, surveillance, air traffic management and control, and safety as crucial categories (security is out of the scope of this study). The results provide for each category a proposal about how to solve the integration and implementation of RPAS in a TMA.

espanolLas nociones de derechos preferentes e intereses de los estados no son ajenas al derecho internacional general o al derecho del mar y, como hipotesis, existe una tendencia sutil y plausible de preferir los ultimos a los primeros al abordar el regimen juridico de los bienes comunes globales. Considerando el patrimonio cultural subacuatico (PCS) entre estos bienes comunes, este articulo analiza como construir un regimen juridico que proteja el PCS abandonando progresivamente la presencia de derechos y su sustitucion por la nocion de interes. Una busqueda de los titulares de este interes y su identificacion in casu a traves de la nocion revisada de vinculo verificable, el contenido y el alcance de sus capacidades juridicas y las responsabilidades que los actores interesados puedan tener (particularmente los Estados), y el regimen juridico que rige todos estos temas son el proposito de estas paginas. Este articulo discutira primero la nocion de derecho preferente como se usa en el derecho internacional y el derecho del mar, en general, seguido por el estudio de la presencia y proyeccion de esa nocion en los instrumentos juridicos internacionales actuales que rigen el PCS. Se seguira el mismo esquema de analisis cuando se aborde la nocion del interes juridico y su desempeno como un concepto operativo tanto a nivel general del derecho internacional como en el derecho del mar para, mas adelante, estudiar como esta nocion puede estar creando una nueva estructura de analisis para la proteccion del PCS. EnglishThe notions of preferential right and interest of states are not alien to general international law or the law of the sea and, as hypothesis, there is a subtle and plausible trend to prefer the later before the former when addressing the legal regime of global commons. Considering the underwater cultural heritage (UCH) as a possible component among these commons, this article discusses how to build up a legal regime protecting UCH progressively abandoning the presence of rights and its substitution by the notion of interest. A quest for the holders of this interest and their identification in casu through the revisited notion of verifiable link, the content and extent of their legal capacities and the responsibilities these stakeholders may have ⎯particularly states⎯, and the legal regime governing all these issues are the purpose of these pages. This article will discuss first the notion of preferential right as used in international law and the law of the sea, in general, followed by the study of the presence and projection of that notion in current international legal texts governing UCH. The same scheme of analysis will be followed when addressing the notion of legal interest and its performance as an operative concept both at the general level of international law and the law of the sea and, later, how this notion may be creating a new legal and political canvas for the protection of UCH.

A detailed list of acanthocephalans from Argentina was generated based on 205 published records. The list includes 52 named and 35 undetermined species of Acanthocephala infecting 6 species of invertebrate (2 amphipods, 3 decapods and 1 insect) and 155 species of vertebrate (one cartilaginous fish, 95 bony fishes, 10 amphibians, 3 reptiles, 13 birds and 33 mammals) host species in the Argentinean territory. The present list contains information on the invertebrate and vertebrate host(s), site of infection, developmental stage and locality(ies) of the acanthocephalans listed and references. For some species of acanthocephalans, information about repositories of the type material, voucher specimens, and DNA sequences of individual taxa are also presented. Finally, a host-Acanthocephala list is also provided. The data compiled revealed considerable gaps in the knowledge of the diversity, taxonomy, distribution, and life cycles of the acanthocephalans from Argentina.

Se realiza una revisión de las diferentes pruebas de laboratorio empleadas para el control de la terapéutica anticoagulante. Se hace especial hincapié en el estudio del trombotest de Owren. Se precisan las particularidades del mismo, técnica, valoración y otros aspectos. Se exponen las ventajas de este test sobre otros empleados hasta ahora.

Se ha realizado la valoración estadística del trombotest de Owren basándose en más de 600 determinaciones del mismo. Se llega a las siguientes conclusiones: 1ª Operando con sangres normales, la exactitud de la técnica es grande, ya que el margen de variación no sobrepasa un segundo. 2.ª A medida que los valores del trombotest van aumentando, el error de la técnica aumenta, llegando a ser el margen de variación de 4 segundos cuando los valores del trombotest alcanzan 80 segundos, aproximadamente. 3.ª Con reactivos congelados se pueden obtener resultados valorables, ya que se comportan como si fueran recientes. La congelación debe ser a menos 25º C. 4.ª A 4º C. el reactivo del trombotest no se conserva en condiciones de ser usado de nuevo. 5.ª Las muestras de sangre se conservan perfectamente durante 36 horas a partir del momento en que se practicaba la extracción. Después de 48 horas, los valores del Trombotest se acortan sensiblemente, por lo que creemos que pasado este período de tiempo, la muestra de sangre no se halla en condiciones de ser usada.

Los aa. han estudiado la adhesividad plaquetar "in vivo" por medio de un método simple, fácilmente realizable en un laboratorio corriente. Consiste en practicar recuentos de plaquetas en sangre venosa y capilar y ver las diferencias numéricas existentes entre ambas. Normalmente estas diferencias oscilan entre 50.000/mm3 y 180.000/mm3, con una disminución porcentual que varía entre 18,1 y 51,4 por 100. Asimismo se observa una disminución progresiva de las plaquetas en las sucesivas gotas que fluyen de la misma herida. Dicha disminución igualmente está en relación con la propiedad de los trombocitos de adherirse entre sí y a la superficie de la herida, con la finalidad de coartar la hemorragia por medio de la formación del tapón hemostático. Durante las investigaciones practicadas se han observado dos casos, caracterizados clínicamente por una púrpura de origen vasculo plaquetar, en los cuales la adhesividad trombocítica estaba francamente disminuida. Basándose en los resultados obtenidos, se ha puesto en evidencia el hecho de que si se quiere realizar un recuento exacto de plaquetas en sangre periférica, conviene hacer las determinaciones sobre la primera gota de sangre que se obtiene después de practicada la incisión.

1. Se estudiaron 30 sujetos considerados normales con la técnica del tiempo de hemorragia secundario, a fin de valorar la misma, habiéndose conseguido unas cifras que oscilaron entre 0 y 5 min. 30 seg. 2. Se investigaron las variaciones del mismo en un grupo de 4 hemofílicos, cuyos tiempos de hemorragia primarios fueron normales. Se obtuvieron unos tiempos de hemorragia secundarios de 9, 12 y 14 min., resultados, como se ve, francamente alterados: lo que nos parece de interés como dato coadyuvante para el diagnóstico de los estados hemofílicos. 3. Asimismo se estudiaron 10 sujetos sometidos a la administración de Sintrom y en los que se pudo comprobar un manifiesto alargamiento de los tiempos de hemorragia primario y secundario tras la administración del mismo. Se estudia el mecanismo fisiopatológico de estas anomalías.

Los autores presentan un caso de cloroma en un niño de ocho años, diagnosticado once meses después del comienzo de la enfermedad. Actualmente se considera el cloroma como una variedad de tumor mieloblástico. El color de las masas tumorales es debido a la verdeperoxidasa. Parece demostrado que la porfirina forma parte de la molécula del fermento.

On the 10-year anniversary of the discovery of induced pluripotent stem cells, we review the main results from their various fields of application, the obstacles encountered during experimentation and the potential applications in clinical practice. The efficacy of induced pluripotent cells in clinical experimentation can be equated to that of human embryonic stem cells; however, unlike stem cells, induced pluripotent cells do not involve the severe ethical difficulties entailed by the need to destroy human embryos to obtain them. The finding of these cells, which was in its day a true scientific milestone worthy of a Nobel Prize in Medicine, is currently enveloped by light and shadow: high hopes for regenerative medicine versus the, as of yet, poorly controlled risks of unpredictable reactions, both in the processes of dedifferentiation and subsequent differentiation to the cell strains employed for therapeutic or experimentation goals.

On the 10-year anniversary of the discovery of induced pluripotent stem cells, we review the main results from their various fields of application, the obstacles encountered during experimentation and the potential applications in clinical practice. The efficacy of induced pluripotent cells in clinical experimentation can be equated to that of human embryonic stem cells; however, unlike stem cells, induced pluripotent cells do not involve the severe ethical difficulties entailed by the need to destroy human embryos to obtain them. The finding of these cells, which was in its day a true scientific milestone worthy of a Nobel Prize in Medicine, is currently enveloped by light and shadow: high hopes for regenerative medicine versus the, as of yet, poorly controlled risks of unpredictable reactions, both in the processes of dedifferentiation and subsequent differentiation to the cell strains employed for therapeutic or experimentation goals.

Se ha estudiado en 10 enfermos, no afectos de hepatopatías, ni de nefropatías, y con ausencia de trastornos de la coagulación o hemostasia, el efecto de la terapéutica anticoagulante con derivados cumarínicos. Ello se hizo midiendo la actividad de los diversos factores. Las caídas más profundas se observaron al 4º día, y afectaron a los factores VII, IX y X. El trombotest de Owren, que muestra en su caída un marcado paralelismo con el IX, se ha mostrado como eficaz elemento de control. Se discuten asimismo los niveles ideales y perjudiciales en la terapéutica anticoagulante.