Family-based intervention to prevent childhood obesity among school-age children of low socioeconomic status: study protocol of the FIVALIN project.

BACKGROUND: Childhood obesity represents a global public health crisis: the number of obese children and adolescents (aged 5-19 years) worldwide has risen tenfold in the past four decades. The vast majority of overweight and obese children live in high-income countries, and low socio-economic status (SES) is a significant risk factor. Family Based Interventions (FBI) have demonstrated positive results in preventing obesity, although these results are strongly influenced by SES. Moreover, we still poorly understand how FBI can determine a positive trend in weight status in low-income communities. Therefore, there is an urgent need to define and evaluate innovative and multi-target projects to reduce obesity risk behaviors and health inequalities and the present study aims to present the study protocol of FIVALIN a FBI that pretends to achieve this goal. METHODS: We will conduct a quasi-experimental design within 60 Community Child Centers (CCC) in Barcelona metropolitan area. Each cluster (CCC) will be assigned by convenience to the intervention and control groups. For the whole study, a total of 810 children aged 8-12 years and 600 parents will be recruited during 3 consecutive editions (1st - 2019/2020; 2nd - 2020/2021; 3rd - 2021/2022) of 10 months each. The action is a regular multicomponent health-promotion intervention targeting children, families, and CCC. All activities are based on the Motivational Interviewing (MI) approach and will focus on promoting good dietary habits, physical activity, appropriate screen time and sleep duration, and psychological well-being. The control group participate in a unique workshop on general awareness of healthy lifestyles for families. We will perform a comparative analysis of the evolution of weight status, healthy lifestyles, and socioeconomic variables, between the intervention and control groups. DISCUSSION: There is a need for more evidence on how to target and evaluate holistic interventions in low SES families. Our multi-targeting intervention for obesity prevention tackles risky behaviors that go beyond diet and physical activity (PA). Therefore, future interventions can effectively promote all the behavioral domains that determine trends in the weight status. TRIAL REGISTRATION: ISRCTN Registry: ISRCRN12682870 . Registered 9 July 2020. Retrospectively registered. Protocol version: 30 April 2021, version 5.

Study of must and wine amino acids composition after seaweed applications to Tempranillo blanco grapevines.

Recently, A.O.C. Rioja have selected and enlisted the Tempranillo blanco as a new grapevine variety to be cultivated in this area. This is the first report that studies amino acid and ammonium composition of grape juice and wine from Tempranillo blanco. The aim was to study the effect of foliar application of a seaweed extract to a Tempranillo blanco vineyard on must and wine amino acids and ammonium content. The results suggested that Tempranillo blanco behaved as an arginine accumulator variety. Biostimulation after seaweed applications at a high dosage (Hd) to the grapevines increased the concentration of several amino acids in the 2017 season, while scarcely affected their content in 2018. Phenylalanine, precursor of several volatile and phenolic compounds, was increased in both seasons after Hd applications. Season was the most important factor in the variability of the must and wine amino acids concentration, followed by treatment and its interaction.

Daño neurológico perioperatorio. Identificación de factores de riesgo, prevención y estudios relacionados / Perioperative nerve injury. Risk factor identification, prevention and work-up

BACKGROUND: Regional anesthesia techniques can have adverse effects, like peripheral nerve injuries. This can affect the practitioner on the choice of techniques when offering multimodal analgesia. CASE REPORT: We present the case of an arthroscopic rotator cuff repair on a patient with no comorbidities who presented peripheral nerve injury during post-op. Initially thought to have occurred as a consequence of the anesthetic technique, further study of the patient revealed the injuries to have been produced by the arthroscopic surgery. CONCLUSION: There are multiple factors that influence the possibility of peripheral nerve injury associated with nerve blocks. They can be grouped as related to the patient, the anesthetic technique or the surgical technique, the latter being the most relevant. If a patient manifests signs of peripheral nerve injury high-resolution magnetic resonance of the neural tissue must be performed immediately. Sensory nerve conduction study and electromyography must be performed 4 weeks after by an expert neurologist.

INTRODUCCIÓN: La anestesia regional puede producir como efecto adverso lesiones de nervios periféricos, lo que puede hacer desistir al anestesiólogo de realizar técnicas que mejoran la analgesia multimodal. CASO CLÍNICO: Se presenta el caso de un paciente sin comorbilidades que se operó de reparación artroscópica del manguito rotador y presentó daño neurológico postoperatorio. Inicialmente se sospechó que el daño había sido producido durante la técnica anestésica, sin embargo, el estudio adecuado demostró que el daño se relacionaba con la técnica quirúrgica. CONCLUSIÓN: Existen factores que influyen en la posibilidad de daño neurológico asociado a bloqueos de nervios periféricos que pueden ser propios del paciente, de la técnica anestésica o quirúrgicos, siendo estos últimos los más relevantes. En un paciente con clínica compatible debe realizarse resonancia magnética del tejido neural de alta resolución de forma inmediata; estudio de conducción neural sensitiva y electromiografía a las 4 semanas de evolución por un neurólogo experto.

Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.

Hipnosis anestésica inducida por profesional de Enfermería. Reporte de un caso / Nursing staff induced anesthetic hypnosis: A case report / Hipnose anestésica induzida por profissional de Enfermagem. Relatório de um caso

Resumen Introducción: La hipnosis anestésica puede ser un recurso útil para procedimientos dolorosos. Desarrollo: Se reporta caso de una joven que requiere exodoncia de terceros molares, con uso de hipnosis como único anestésico. El proceso de enfermería inicia con la valoración según patrones funcionales, impresiona lo sana que se encuentra, sin antecedentes mórbidos relevantes ni contraindicación para anestesia química. Se selecciona diagnóstico NANDA de Disposición para mejorar el confort. Dentro del plan se incorporan el NIC 5920 Hipnosis y 5922 Facilitar la autohipnosis, con buena evolución según lo planificado. Resultados: La extracción con hipnosis anestésica se desarrolló de forma similar a la cirugía con anestesia química, la cual se realizó sin dolor. En posoperatorio, paciente practica autohipnosis, sin necesitar analgésicos y evolucionó favorablemente. Discusión: La hipnosis requiere mayor evidencia científica, pero su uso es prometedor. Se constataron los beneficios de la hipnosis en el abordaje del dolor. Conclusión: La hipnosis anestésica, fue útil como intervención de enfermería en cirugía dental. La autohipnosis contribuyó al buen resultado. El profesional de Enfermería entrenado en hipnosis está en condiciones de incorporarla en la gestión del cuidado. El caso resulta interesante, dado que la paciente opta por la hipnosis, sin contraindicación para anestesia química, ya que no se encontró otro reporte de hipnoanestesia inducida por profesional de Enfermería, como anestésico único. Anecdóticamente, durante la filmación del procedimiento, una periodista entra espontáneamente en trance, por lo que requiere intervención del profesional de Enfermería para salir de él.

Abstract Introduction: Anesthetic hypnosis can be a useful resource to address painful procedures. Development: The case is of a young female patient requiring third-molars exodontia who underwent it under anesthetic hypnosis. The nursing process began with the assessment according to functional patterns. The patient was found healthy and without relevant morbid antecedents nor drug-anesthesia contraindications. A comfort improving disposition NANDA diagnosis was selected. NIC 5922 and 5920 were incorporated to the intervention plan. Results: The extraction under anesthetic hypnosis was performed in a similar form in comparison to a drug-anesthesia extraction procedure. During the post operatory stage, the patient used self-hypnosis and responded favorably without analgesics. Discussion: While hypnosis requires more scientific evidence, its use appears to be promising. In this case, diverse benefits from using hypnosis to address a painful procedure were acknowledged. Conclusion: Anesthetic hypnosis proved being helpful in a dental-surgery related nursing intervention. Self-hypnosis also contributed to the favorable outcome. A nursing professional who is well trained in hypnosis can incorporate this kind of procedure into her care management approach. This particular case was interesting because the patient chose hypnosis over drug anesthesia, and no other report on a nursing staff induced anesthetic hypnosis was found. Anecdotally, during the filming of this procedure, a journalist suffered an emotional trance which required immediate nursing intervention.

Resumo Introdução: A hipnose anestésica pode ser um recurso útil para procedimentos dolorosos. Desenvolvimento: Informa-se o caso de uma garota que requer exodontia de terceiros molares, com uso de hipnoses como único anestésico. O processo de enfermagem inicia com a valoração segundo padrões funcionais, impressiona o saudável que se encontra, sem antecedentes mórbidos relevantes nem contraindicação para anestesia química. Seleciona-se diagnóstico NANDA de Disposição para melhorar o conforto. Dentro do plano se incorporam o NIC 5920 Hipnose e 5922 Facilitar a auto-hipnose, com boa evolução segundo o planejado. Resultados: A extração com hipnose anestésica desenvolveu-se de forma similar à cirurgia com anestesia química, a qual se realizou sem dor. Em pós-operatório, o paciente prática auto-hipnose, sem precisar analgésicos e evolucionou favoravelmente. Discussão: A hipnose requer maior evidencia científica, mas seu uso é promissor. Verificaram os benefícios da hipnose na abordagem da dor. Conclusão: A hipnose anestésica foi útil como intervenção de enfermagem em cirurgia dental. A auto-hipnose contribuiu para o bom resultado. O profissional de Enfermagem treinado em hipnose está em condições de incorporá-la na gestão do cuidado. O caso resulta interessante, dado que a paciente opta pela hipnose, sem contraindicação para anestesia química, já que não se encontrou outro relatório de hipnoanestesia induzida por profissional de Enfermagem, como anestésico único. Anedoticamente, durante a filmagem do procedimento, uma jornalista entrou espontaneamente em transe, pelo qual se requereu intervenção do profissional de Enfermagem para sair dele.

NATURAL RADIUM ISOTOPES PRESENT IN SOME COSMETIC PRODUCTS: DETERMINATION OF ACTIVITY CONCENTRATION AND DOSE ESTIMATION.

Since the early days, clays, plant extracts and raw materials have been used for therapeutic and beauty purposes. Nowadays, this use is widely spread, as a huge amount of companies have developed new cosmetics based on natural sources. This may lead to an accumulation of radionuclides that can be hazardous for people. Especially dangerous are radium isotopes (226,228Ra), which can be part of the raw materials that cosmetics are made from. In this paper, the concentration of radium isotopes of 18 natural cosmetics was determined. Concentrations resulted in the range 7.9 ± 5.0-37.6 ± 12.5 Bq kg-1 for 226Ra; and 2.5 ± 1.7-35.4 ± 2.6 Bq kg-1 for 228Ra. The effective dose in the skin has been estimated, obtaining a mean value of 13.1 ± 4.9 µSv y-1. This value is far from the reference level of 50 mSv y-1 for the public members. Therefore, no radiological risk derived from the use of these samples, has been found.

Biomarkers of carotenoid bioavailability.

The use of biomarkers constitutes an essential tool to assess the bioavailability of carotenoids in humans. The present article aims to review several methodological, host-related and modulating factors relevant on assessing and interpreting carotenoid bioavailability. Markers for carotenoid bioavailability can be broadly divided into direct, biochemical or "analytical" markers and indirect, physiological or "functional" indicators. Analytical markers usually refer to biochemical indicators of intake and/or status (short and long term exposure) while functional measures may be interpreted in terms of cumulative exposure, biological effect (bioactivity) or modification of risk factors. Both types of markers display advantages and limitations but, in general, a relationship exists among the type of marker, the biological specimen needed and the time required for a change. Humans may absorb a wide range of carotenes and xanthophylls and many of them may be found in serum and tissues. However, under physiological conditions, the several classes of dietary carotenoids may behave unequally leading to a different systemic profile and, moreover, they can be selectively accumulated at target tissues. In addition, some carotenoids may be chemically and enzymatically modified generating different oxidative metabolites and apocarotenoids. Quantitatively, the biological response upon carotenoid intervention (assessed by analytical and functional markers) is highly variable but the use of large doses and long-term protocols may lead to saturation effects and the loss of linearity in the response. Also, despite carotenoid exposition is considered to be safe, markers of overexposure include clinical signs (i.e. carotenodermia, corneal rings and retinopathy) and biochemical indicators (hypercarotenemia, xanthophyll esters). Overall, both host-related and methodological factors may influence analytical and functional markers to assess carotenoid bioavailability although the different subclasses of carotenoids may not be equally affected.

The impacts of temperature, alcoholic degree and amino acids content on biogenic amines and their precursor amino acids content in red wine.

The aim was to study how factors such as temperature, alcoholic degree, and amino acids supplementation are able to influence the content of tyramine, histamine, 2-phenylethylamine, tryptamine and their precursor amino acids in winemaking process. Biogenic amines and amino acids were quantified at the beginning, middle and end of alcoholic fermentation, and at the end of malolactic fermentation. In general, samples produced with amino acid supplementation did not show the highest concentrations of biogenic amines, except for histamine, which content increased with the addition of the four amino acids. The synthesis of tyramine was mainly affected by the temperature and alcoholic degree, the formation of phenylethylamine was largely influenced by alcoholic degree, and tryptamine synthesis principally depended on temperature. Interestingly, there was interaction between these three factors for the biogenic amines studied. In conclusion, winemaking conditions should be established depending on the biogenic amine which synthesis is required to be controlled.

Hipnosis clínica para mejorar la disposición a la curación de un paciente en la unidad de cuidados intensivos / Clinical hypnosis to improve a patient's disposition to receive treatment in an ICU / Hipnose clínica para melhorar a disposição à cura de um paciente em UCI

En el presente artículo se revisa el caso de una persona adulta hospitalizada en una unidad de paciente crítico, quien ha evolucionado con agitación durante la estadía hospitalaria y que requiere curación de úlceras por presión. A la valoración la enfermera se anticipa a la reacción negativa que podría tener el paciente ante el dolor asociado a la técnica, por lo cual utiliza la hipnosis clínica con el objetivo de favorecer la disposición del paciente a mejorar su comodidad; para lograr realizar la curación sin signos de dolor en la monitorización ni en el reporte subjetivo, se constata el mejoramiento del bienestar general del paciente relacionado con la relajación involucrada en el proceso. Se presenta el proceso de enfermería, la descripción del procedimiento y se motiva a los profesionales de enfermería a incorporar la hipnosis dentro de su repertorio de competencias para la gestión del cuidado.

In this article, we review the case of an adult person hospitalized in a critical patient unit, who has become agitated, and who requires treatment for pressure sores. During assessment, the nurse anticipates the patient's possible negative reaction associated to the pain, and thus uses the clinical hypnosis technique in order to favor the patient's better disposition. This procedure improved the patient's comfort, and the healing treatment was performed without signs of pain. As a result of the enhanced relaxation, the patient's overall wellbeing was ensured. The nursing process is presented as well as the specific procedure. Nursing professionals are encouraged to incorporate the hypnosis into their competences repertoire for the care management.

No presente artigo revisa-se o caso de uma pessoa adulta hospitalizada em uma unidade de paciente crítico, quem tem evoluído com agitação durante a estadia hospitalar e que requer cura de úlceras por pressão. À avaliação, a enfermeira antecipa-se à reação negativa que poderia ter o paciente perante a dor associada à técnica, pelo qual utiliza a hipnose clínica com o objetivo de favorecer a disposição do paciente para melhorar seu conforto, consegue-se realizar a cura sem signos de dor na monitorizarão nem no relatório subjetivo, constata-se a melhora do bem-estar geral do paciente relacionado com a relaxação envolvida no processo. Apresenta-se o processo de enfermagem, a descrição do procedimento e motiva-se aos profissionais de enfermagem a incorporar a hipnose dentro de seu repertório de competências para a gestão do cuidado.

Prevalence of hypercalcemia related to hypervitaminosis D in clinical practice.

BACKGROUND & AIMS: Recent interest in vitamin D has led to a substantial increase in the use of vitamin D supplements. Vitamin D intoxication may be a concern as hypervitaminosis D can result in irreversible calcification of soft tissues so that it is important to detect early markers of vitamin D intoxication. Our aim was to assess the simultaneous presence of biochemical markers of vitamin D toxicity (i.e. hypervitaminosis D, hypercalcemia) and determine the concentrations of 25-OH-vitamin D at which the risk of hypercalcemia, and thus toxicity, might begin. METHODS: We evaluated retrospectively a 6-year period during which 25.567 samples were assessed for 25-OH-vitamin D status by UHPLC. Hypervitaminosis D was defined at serum 25-OH-vitamin D >160 nmol/L. Serum and urine calcium, phosphorus and iPTH were also recorded, if available. Medical history revision was performed in subjects displaying simultaneously hypervitaminosis D and hypercalcemia. RESULTS: Overall, hypervitaminosis D was found in 475 samples (1.86%) of which 51 displayed hypercalcemia (11.1%). A total of 382 samples were identified as the first record of hypervitaminosis D and 39 presented hypercalcemia (10.2%), most of them at 25-OH-vitamin D levels between 161 and 375 nmol/L. Only in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l. In no case, serum calcium achieved concentrations considered as critical values (>13 mg/dl). CONCLUSION: Hypercalcemia due to vitamin D represented <4% of the total hypervitaminosis D detected and <0.1% of the tests performed. However, a highly variable response was observed and most subjects presented hypercalcemia at serum concentrations of 25-OH-vitamin D < 375 nmol/L.

Primary care randomized clinical trial: manual therapy effectiveness in comparison with TENS in patients with neck pain.

This study investigated effectiveness of manual therapy (MT) with transcutaneous electrical nerve stimulation (TENS) to reduce pain intensity in patients with mechanical neck disorder (MND). A randomized multi-centered controlled clinical trial was performed in 12 Primary Care Physiotherapy Units in Madrid Region. Ninety patients were included with diagnoses of subacute or chronic MND without neurological damage, 47 patients received MT and 43 TENS. The primary outcome was pain intensity measured in millimeters using the Visual Analogue Scale (VAS). Also disability, quality of life, adverse effects and sociodemographic and prognosis variables were measured. Three evaluations were performed (before, when the procedure finished and six months after). Seventy-one patients (79%) completed the follow-up measurement at six months. In more than half of the treated patients the procedure had a clinically relevant "short term" result after having ended the intervention, when either MT or TENS was used. The success rate decreased to one-third of the patients 6 months after the intervention. No differences can be found in the reduction of pain, in the decrease of disability nor in the quality of life between both therapies. Both analyzed physiotherapy techniques produce a short-term pain reduction that is clinically relevant.

Evaluación del contenido de esteviósido y rebaudiósido A en una población de Stevia rebaudiana Bertoni (kaâ heê) cultivada comercialmente: estudio preliminar / Evaluation of the content of stevioside and rebaudioside A in a population of Stevia rebaudiana Bertoni (kaâ heê) commercially cultivated: a preliminary study

Stevia rebaudiana Bertoni (kaâ heê) es un arbusto originario de la Región Oriental de Paraguay. Sus hojas contienen glucósidos diterpénicos que producen un sabor dulce, perosin valor calórico y son de 150 a 300 veces más dulces que la sacarosa (solución al 0,4%). Durante las temporadas agrícolas 1998 y 1999 se establecieron sembrados deselección individual, en el Instituto Agronómico Nacional (Caacupé, Paraguay). El objetivo de este trabajo fue determinar el contenido de esteviósido y rebaudiósido A en plantasseleccionadas en campo a fin de evaluar la variabilidad existente en la población e identificar clones con alto contenido de dichos glucósidos. De una población original de 2000 individuos, se seleccionaron fenotípicamente 140 plantas por características agronómicas superiores y se cosecharon en etapa de prefloración y libres de polinización.En los Laboratorios del Instituto Nacional de Tecnología Normalización y Metrología (INTN) fueron evaluados los contenidos de esteviósido y rebaudiósido A por detección por cromatografía liquida de alta resolución. El contenido de esteviósido fluctuó entre 0 y 21 % concentrándose el 92 % de la población entre valores del 5 al 15 % .En cuanto al contenido de rebaudiósido A se obtuvieron valores entre 0 y 12 % correspondiendo al 68% de la población un contenido entre 3 y 9 %. La demanda actual de stevia se halla en creciente aumento, por lo que las acciones orientadas a establecer líneas clonales con alto contenido de principios edulcorantes permitirá a los productores primarios la obtención decultivos más productivos e incrementara el rendimiento de obtención de glucósidos.

Stevia rebaudiana Bertoni (kaâ heê) is a bush native to the Eastern Region of Paraguay. Its leaves contain diterpene glycosides that produce a sweet taste but without any caloric value and are 150 to 300 times sweeter than sacharose (0, 4% solution). During 1998 and 1999 agricultural seasons, individual selection sown fields were established in the National Agronomical Institute (Caacupé, Paraguay). The objective of this work was todetermine the content of stevioside and rebaudioside A in these selected plants in the field in order to evaluate the variability existent in the population and identify clones with high content of those glycosides. Of an original population of 2,000 specimens, 140 plants were selected phenotipically by the superior agronomical characteristics and they were harvested in the period of pre-flowering and were pollination free. The content of stevioside and rebaudioside A were evaluated in the laboratories of the National Instituteof Technology, Standardization and Metrology (INTN in Spanish) by high resolution liquid chromatography. The content of stevioside ranged from 0 to 21% concentrating the 92% of the population between 5 to 15%. In relation to rebaudioside A, values between 0 and 12% were obtained being 68% of the population between a content of 3 to 9%. As the current demand of Stevia is increasingly rising, the actions oriented to establish clonallines with high content of sweetener principles will allow primary producers to obtain more productive cultivations and increase the output of glycoside obtainment.

Glucokinase and glucokinase regulatory proteins are functionally coexpressed before birth in the rat brain.

Our previous description of functional glucokinase (GK) isoforms and their interactions with glucokinase regulatory protein (GKRP) in adult rat and human brains suggested that both participate in glucose sensing in the central nervous system. To determine whether both proteins are coexpressed and active before birth or during early post-natal life, we characterised these molecules in the brains of foetal and post-natal pup rats. We found GK and GKRP mRNAs that were similar to those previously reported in the adult rat brain. Likewise, GK and GKRP gene expression gave rise to proteins of 52 and 69 kDa, respectively. Immunohistochemistry experiments showed the colocalisation of both GK and GKRP proteins in the same brain cells of 21-day-old rat foetuses. Furthermore, coprecipitation of GK and GKRP in the presence of fructose 6-phosphate suggests interactions between both proteins. The presence of GK phosphorylating activity was detected in different brain areas of 21-day-old foetuses with a contribution to the total glucose-phosphorylating activity of between 17.2 +/- 1.7% and 12.4 +/- 3.7%, with the hypothalamus being the region of maximum activity. The hypothalamic GK activity in 21-day-old foetuses has a high apparent K(m) for glucose and no product inhibition by glucose 6-phosphate. Our findings indicate that both proteins may be functionally active before birth and that they can act within a glucose sensor system involved in controlling food intake.

The quest for Factor VIIa exosite inhibitors.

Coagulation proteases are involved in a highly orchestrated proteolytic cascade which is essential for haemostasis and blood clotting. In particular, the initiator of the coagulation cascade, Factor VIIa, binds to its cofactor, tissue factor, and its substrate, Factor X, via exosite interactions to form a ternary catalytic complex named extrinsic Xase. These exosite interactions have also been shown to allosterically induce the active conformation of the catalytic site of Factor VIIa. We have developed a direct continuous fluorescence polarization-based extrinsic Xase assay, which has been used to screen in excess of 1 million structurally diverse low-molecular-mass compounds as a potential starting point for the development of anticoagulants. The primary screen hits were categorized with deconvolution assays into either active-site or exosite inhibitors. The latter category of hits displayed both competitive and uncompetitive modalities of inhibition with respect to Factor X activation. An uncompetitive mechanism of action is of particular interest as it offers a hypothetical inhibitory advantage in the context of inhibiting a proteolytic cascade such as the blood coagulation pathway.

Identification and physical mapping of induced translocation breakpoints involving chromosome 1R in rye.

To obtain translocations involving specific chromosomes in rye, pollen of a line in which chromosome 1R has large C-bands on its two telomeres, but which lacks C-bands (or has very small ones) on the telomeres of the remaining chromosomes, was X-irradiated. All translocations involving the labelled chromosome (1R) could be easily recognized in C-banded mitotic metaphases. The non-labelled chromosome involved in each translocation was identified either from mitotic C-banding analysis or from the meiotic configurations observed in some specific progenies. A physical map including 40 translocation breakpoints has been developed by means of synaptonemal complex (SC) analysis of well-paired pachytene quadrivalents. The results agree with the hypothesis of chromosomes 2R to 7R having similar probabilities of participating in translocations with chromosome 1R. However, the locations of the breakpoints are not entirely random: an excess of translocation breakpoints located on the short arm of chromosome 1R was obtained, and the two acentric translocated segments of each translocation show a trend towards having similar sizes. The possible reasons for these two non-random situations are discussed.

Effects of policosanol on patients with ischemic stroke: a pilot open study.

Stroke is a major health problem worldwide. Its pharmacological management includes thrombolytic therapy for the acute phase and antiplatelet drugs for stroke recovery and prevention. Statins can help in the acute phase and in preventing stroke in secondary prevention patients. Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects, with protective effects in stroke models. This observational study investigated the effects of policosanol (20 mg/day) administered during the acute phase and for 5 years later on the neurological recovery of patients with ischemic stroke treated with antiplatelets and vitamins. After hospital discharge, patients were followed up every 3 (first year) and 6 (thereafter) months. Neurological improvement was assessed with the modified Canadian Neurological Scale. Adverse events were recorded. Fifty patients were included; all completed the study. Neurological score improved throughout the study. No patient died, and most [40 (80.0%)] did not experience new vascular events; only one (2.0%) suffered a new stroke, and two (4.0%) suffered more than one transient ischemic attack. The time to the first recurrent event was 46.2 months. Policosanol persistently lowered serum total cholesterol, with such reduction correlating with the neurological improvement (R = 0.995253301). Triglycerides were unchanged. Treatment was well tolerated. Policosanol administered to patients suffering ischemic stroke treated with aspirin and vitamins showed good results on neurological outcomes and recurrent events. This study, however, has limitations, since it was open and uncontrolled, and patients also consumed aspirin and vitamins. New randomized, controlled studies are needed to assess the usefulness of policosanol in stroke management.

GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis.

BACKGROUND: Guanidinoactetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis. The authors analyzed clinical, biochemical, and molecular findings in 27 patients. METHODS: The authors collected data from questionnaires and literature reports. A score including degree of intellectual disability, epileptic seizures, and movement disorder was developed and used to classify clinical phenotype as severe, moderate, or mild. Score and biochemical data were assessed before and during treatment with oral creatine substitution alone or with additional dietary arginine restriction and ornithine supplementation. RESULTS: Intellectual disability, epileptic seizures, guanidinoacetate accumulation in body fluids, and deficiency of brain creatine were common in all 27 patients. Twelve patients had severe, 12 patients had moderate, and three patients had mild clinical phenotype. Twenty-one of 27 (78%) patients had severe intellectual disability (estimated IQ 20 to 34). There was no obvious correlation between severity of the clinical phenotype, guanidinoacetate accumulation in body fluids, and GAMT mutations. Treatment resulted in almost normalized cerebral creatine levels, reduced guanidinoacetate accumulation, and in improvement of epilepsy and movement disorder, whereas the degree of intellectual disability remained unchanged. CONCLUSION: Guanidinoactetate methyltransferase deficiency should be considered in patients with unexplained intellectual disability, and urinary guanidinoacetate should be determined as an initial diagnostic approach.

Implicaciones clinicoterapéuticas de la deficiencia de yodo en España / Clinical and therapeutic implications of iodine deficiency in Spain

El yodo es un nutriente imprescindible para el organismo humano (esencial para la formación de las hormonas tiroideas), cuya principal fuente de abastecimiento son los pescados de mar y los mariscos; se precisa una ingesta diaria mínima de 100 mg en la primera infancia, 120 hasta la pubertad, 150 en la edad adulta y no menos de 250 durante el embarazo y la lactancia. Hoy día, la Organización Mundial de la Salud estima en más de 2.200 millones de personas en riesgo por habitar en áreas yododeficientes, entre las que se incluye una gran parte de Europa. En España, los estudios realizados confirman también este déficit, que es leve en la población escolar de todas las comunidades autónomas estudiadas, salvo en Asturias, donde el programa de profilaxis con sal yodada iniciado en 1983 ha mostrado tener eficacia. Las gestantes, sin embargo, son el segmento de población más vulnerable, y presentan una marcada deficiencia, que se manifiesta también en los recién nacidos, demostrada por los valores de tirotropina (TSH). Aunque sólo hay 2 estudios en preescolares (Mataró y Asturias), ambos sugieren un estado de nutrición aceptable. Se sabe que la reducción de los trastornos por deficiencia de yodo como grave problema de salud pública ha sido posible con el cambio de los hábitos alimentarios de la población mundial, lo que indica la necesidad de lograr que el consumo de sal yodada en España sea una realidad que alcance al 95% de las familias y, además, que las gestantes y las madres en período de lactancia utilicen suplementos farmacológicos de yodo

Iodine is an essential nutrient for the human organism (for the formation of thyroid hormones), and its main sources are fish and shellfish, requiring a daily minimal intake of 100 micrograms in early childhood, 120 until puberty, 150 in adulthood and not less than 250 during pregnancy and breastfeeding. The World Health Organization estimates that currently 2,200 million persons are at risk for iodine deficiency as they live in iodine-deficient areas, which include a large part of Europe. Studies performed in Spain confirm this deficiency in our country, which is mild in the school-aged population of all the autonomous communities studied, except in Asturias, where the prophylaxis program with iodized salt initiated in 1983 has been shown to be effective. Pregnant women, however, are the most vulnerable segment of the population and show marked iodine deficiency. This deficiency is also manifested in newborns, demonstrated by thyroid-stimulating hormone levels. Although only two studies have been performed in preschool children (Mataró and Asturias) both suggest acceptable nutritional status. It is known that a reduction in iodine deficiency disorders as a serious public health problem can be achieved with a change in diet in the world population, indicating the need to make iodine intake a reality in Spain. Such an intervention should include 95% of families; moreover, pregnant and breastfeeding women should use iodine supplements

Immunobiological features of the galactoside lectin L-Lc isolated from the Argentine mistletoe Ligaria cuneifolia.

Ligaria cuneifolia has been used in Argentine folk medicine and is currently employed as substitute for the European mistletoe (Viscum album) as hypotensor agent. Extracts from V. album are widely used in cancer therapy and the antineoplasic effect is attributed to their cytostatic/cytotoxic and immunomodulatory actions. When studying immunomodulatory effects of L. cuneifolia extracts (Lc extracts), they inhibited proliferation of murine mitogen-activated lymphocytes, leukaemic lymphocytes (LB) and breast tumour cells (MMT). The aim of this work was to isolate and identify lectins from Lc extracts and investigate their immunobiological actions. A galactoside lectin (L-Lc) of 57 kDa was isolated. A polyclonal antiserum obtained against Lc extract recognised both L-Lc and MLI (V. album lectin), suggesting the possibility of shared epitopes. Treatment of LB tumour cells with L-Lc (0.01 and 0.1 microg/ml) produced up to 40.0+/-6.9% inhibition of cell growth, which seems partly mediated by apoptosis (apoptosis of L-Lc treated cells 58.4+/-10.3% versus non-treated cells 38.1+/-8.8%; P<0.05), analysed by acridine orange and ethidium bromide staining. Inhibitory effect on ConA stimulated splenocyte growth was non-significant, while a mitogenic effect was observed on normal murine splenocytes and MMT cells. L-Lc in non-cytotoxic concentrations (250 ng/ml) modified mRNA expression of IL-10 but neither that of TGF-beta nor of IL-2 produced by LB cells. In addition, 43.9+/-0.5% reduction in NO production by LPS-stimulated murine macrophages was found. Finally, survival rates of LB tumour-bearing mice treated or not with Lc extract or L-Lc failed to show significant differences.

Immunomodulating properties of Argentine plants with ethnomedicinal use.

Five Argentine medicinal plants selected according to folk traditional or ethnomedical use, references and primary pharmacological screening; were chosen to elucidate their immunomodulating properties. Dichloromethane, methanolic and aqueous extracts of the aerial parts of Achyrocline flaccida (A. flaccida), Eupatorium arnottianum (E. arnottianum) and Eupatorioum buniifolium (E. buniifolium), leaves of Lithraea molleoides (L. molleoides) and leaves and stems of Phyllanthus sellowianus (P. sellowianus) were analyzed to disclose their effects on murine normal and tumor cell growth as well as on complement hemolytic activity. Modulation of cell growth was evaluated by tritiated thymidine incorporation while inhibition of complement activity was measured on both classical and alternative complement pathways (CP and AP respectively). The results obtained show that most of the extracts exerted inhibitory effect on tumor as well as on mitogen activated normal spleen cell growth. On tumor cells, IC50 ranged between 1-75 microg/ml for most of the extracts with the exception of dichloromethane of L. molleoides and P. sellowianus which required concentrations higher than 100 microg/ml to produce the effect. On mitogenic activated splenocytes, IC50 ranged between < 1 to 85 microg/ml with the exception of methanolic extract of E. buniifolium or P. sellowianus which were not effective on ConA or LPS stimulated splenocytes respectively. Only E. buniifolium was active on murine normal splenocytes proliferation (IC50 0.5-1.5 microg/ml). Finally, one (7%) of 15 extracts showed inhibition of complement activity on CP and 6 extracts (40%) presented moderate activity on CP. The dichloromethane extract of E. arnottianum was the most active (IC50 5 microg/ml), although remarkable effect was also obtained with dichloromethane and methanolic extracts of P. sellowianus (IC50 11.2 and 17.3 microg/ml respectively). Besides, 2 extracts (13%), dichloromethane extract of E. arnottianum and aqueous extract of P. sellowianus, showed moderate inhibition on AP.