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This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms.

Purpose of the research Cognitive stimulation (CS) is defined as activities that involve cognitive processing, usually conducted in a social context and often in a group. This study aims to evaluate the effects of a personalized-adapted CS program in older adults on global cognition, neuropsychological constructs, activities of daily living (ADLs), and mood. Materials and methods The randomized controlled single-blind trial involving 337 participants (235 women and 102 men) ≥ 65 years of age in a Primary Care centre classified participants into 4 groups: 101 for the no deterioration (ND) group; 100 for the subjective cognitive impairment (SCI) group; 108 for the level deterioration (LD) group and 28 for the moderate deterioration group. The intervention consisted of a personalized CS adapted program for 10 weeks. Follow-up assessments were conducted post-intervention, and at 6 and 12 months. The primary outcome was global cognition measured by the Spanish version of the Mini-Mental State Examination. The secondary outcomes were measured by the Barthel Index, the Lawton and Brody Scale, the Goldberg Questionnaire (anxiety sub-scale) and the abbreviated Yesavage Geriatric Depression Scale. Results The intervention showed a tendency of improvement on global cognition and different cognitive functions for groups with no deterioration or level deterioration. The group with moderate deterioration improved in anxiety. Conclusions The findings demonstrated benefits in global cognition, different cognitive functions, semantic fluency, IADLs and anxiety. The most benefits are given in the intermediate groups, SCI, and LD. Moreover, the intervention works by increasing the benefits in the different phases.

The number of children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) in giftedness is higher than that of the normotypic population. This study aimed to analyze the empirical evidence that shows the coexistence, or not, of both diagnoses. The results found did not allow to affirm that ADHD is a valid construction in the context of the giftedness. When studied from a psychobiological perspective it is found that gifted children can present clinical symptoms of ADHD in the absence of specific neuronal markers to this disorder, indeed they seem to follow an different development trajectory. It suggests the need to use neuroscientific and objective approaches that help to understand giftedness and ADHD within the context of neurodevelopment and as a consequence of an integrated and multifaceted organ that is more than a simple reflection of its separate parts or the sum of specific symptoms.

Background and Purpose The lack of cognitive activity accelerates age cognitive decline. Cognitive stimulation (CS) tries to enhance cognitive functioning. The purpose of this systematic review and meta-analysis was to evaluate the effects of CS on cognitive outcomes (general cognitive functioning and specific cognitive domains) in older adults (aged 65 years or older, cognitively healthy participants, or with mild cognitive impairment, or dementia). Methods PubMed, Scopus and Web of Science databases were examined from inception to October 2021. A total of 1,997 studies were identified in these databases, and. 33 studies were finally included in the systematic review and the meta-analysis. Raw means and standard deviations were used for continuous outcomes. Publication bias was examined by Egger's Regression Test for Funnel Plot Asymmetry and the quality assessment tools from the National Institutes of Health. Results CS significantly improves general cognitive functioning (mean difference=MD = 1.536, 95%CI, 0.832 to 2.240), memory (MD = 0.365, 95%CI, 0.300 to 0.430), orientation (MD = 0.428, 95%CI, 0.306 to 0.550), praxis (MD = 0.278, 95%CI, 0.094 to 0.462) and calculation (MD = 0.228, 95%CI, 0.112 to 0.343). Conclusion CS seems to increase general cognitive functioning, memory, orientation, praxis, and calculation in older adults.

Objective: The objective of this study was to evaluate the prevalence and incidence of accidents with biological material, the level of knowledge, and compliance to standard precautions (SPs) among dentists, physicians, nurses, and dental and medical students. Methods: A closed cohort study with a prospective and retrospective component was conducted between August 2014 and September 2015. The participants were contacted in two moments during the follow-up period, during which a structured questionnaire divided into six sections was used; the interviews were conducted during the follow-up period (Month 6) and at the end of the observation period (Month 12). Results: The global prevalence of accidents in the previous 12 months was 10.2%, with a difference between professionals and students (13.0% vs. 5.1%, respectively; p

Gifted people are endowed with a more efficient cognitive system, and capable of achieving objectives with fewer resources. The proper development of this potential is an important determinant for health and social and personal well-being. The aim of this work is to collect and analyse the latest findings on the underlying neurobiological mechanisms. Studies of genetic associations have identified genes and genetic loci that generate cellular properties associated with intelligence. The appearance of transcriptomics and cellular neuroscience provide data on the differential development of brain cells associated with giftedness. Brain imaging studies provide us with a macroscopic, structural, and functional vision of the areas involved in intelligence. The neuro-computational models of cognitive development try to explain the trajectories of development in terms of polygenicity and variations in the level of environmental stimulation.

We evaluated whether the Andean and the Atlantic forests acted as refugia during the Quaternary, and tested biogeographic hypotheses about the regions involved in the connectivity between those biomes (through the Chaco or the Cerrado). To achieve these goals we selected the Buff-browed Foliage-gleaner Syndactyla rufosuperciliata (Aves, Furnariidae) as a study system, a taxon distributed between the Andean and Atlantic forest. We first explored the historical connectivity between regions through niche modeling. We subsequently used DNA sequences (n = 71 individuals) and genomic analyses (ddRADseq, n = 33 individuals) to evaluate population genetic structure and gene flow within this species. Finally, we performed population model selection using Approximate Bayesian Computation. Our findings indicate that the Andean and the Atlantic forests acted as refugia, and that the populations of the focal species from both regions contacted through the Cerrado region, thus suggesting that the historical dynamics of Andean and Atlantic forests are important for the evolution of forest birds in the region. The results are in agreement with studies of other organisms and may indicate a more general pattern of connectivity among biomes in the Neotropics. Finally, we recommend recognizing both the Andean and the Altantic forests lineages of S. rufosuperciliata as independent species.

Given the correlation between poverty and belonging to certain ethnic groups found by previous studies, the present study intends to apply a statistical technique to analyze the differences in intelligence on the basics of Raven's Coloured Progressive Matrices performance between indigenous children and non-indigenous children from poor rural populations when indigenous children are “treated” as (equated) non-indigenous children in terms of nutrition, maternal education and schooling. This cross-sectional study used the Oaxaca-Blinder decomposition to construct a counterfactual with which to compare both groups, distinguishing between differences due to certain characteristics of the child and those differences that are unexplained by the previous differences. The present study was carried out with a sample N = 1804 of 1460 non-indigenous and 344 indigenous children, aged between 5 and 11 years, from poor rural environments in Mexico who participated and completed a reduced version of the Raven's test of intelligence. The results indicate that, when cognitive performance was equated by age and height of the child, education level of the head of the family, help in school work, and care at home, the observed differences in such performance without being equated was reduced.

ZRSR2 is a splicing factor essential for 3’ss recognition of U12-type introns and is frequently mutated in myeloid malignancies and in several tumors. To explore the biological role of ZRSR2 we generated three Zrsr2 mutant mice with deletions localized immediately after the AUG initiation and in two splicing sensitive elements present in the two zinc finger domains. The three Zrsr2 mutant mice exhibited muscle weakness, blood cell anomalies, and in the 2 lines with zinc finger mutations, oogenesis was blocked at the secondary follicle stage. RNA-seq of Zrsr2mu follicles showed aberrations in gene expression and biological pathways, and showed altered alternative splicing (AS) events involving enrichment of U2 and U12-type intron retention (IR), suggesting a functional crosstalk between the major and minor spliceosomes. These results suggest that ZRSR2 is essential for efficient U12 intron splicing and reveals that AS regulation of U12 introns constitute a potential underlying mechanism governing oogenesis.

Bacillus thuringiensis Cry toxins are used worldwide for controlling insects. Cry1Ab is produced as a 130-kDa protoxin that is activated by proteolytic removal of an inert 500 amino-acid-long C-terminal region, enabling the activated toxin to bind to insect midgut receptor proteins, leading to its membrane insertion and pore formation. It has been proposed that the C-terminal region is only involved in toxin crystallization, but its role in receptor binding is undefined. Here we show that the C-terminal region of Cry1Ab protoxin provides additional binding sites for alkaline phosphatase (ALP) and aminopeptidase N (APN) insect receptors. ELISA, ligand blot, surface plasmon resonance, and pulldown assays revealed that the Cry1Ab C-terminal region binds to both ALP and APN but not to cadherin. Thus, the C-terminal region provided a higher binding affinity of the protoxin to the gut membrane that correlated with higher toxicity of protoxin than activated toxin. Moreover, Cry1Ab domain II loop 2 or 3 mutations reduced binding of the protoxin to cadherin but not to ALP or APN, supporting the idea that protoxins have additional binding sites. These results imply that two different regions mediate the binding of Cry1Ab protoxin to membrane receptors, one located in domain II–III of the toxin and another in its C-terminal region, suggesting an active role of the C-terminal protoxin fragment in the mode of action of Cry toxins. These results suggest that future manipulations of the C-terminal protoxin region could alter the specificity and increase the toxicity of B. thuringiensis proteins.

Background Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic condition encountered in many different clinical settings; it generally occurs in the context of hypertensive crisis, immunosuppressive therapy, or autoimmune diseases. It is characterized by headache, stupor, seizures, and visual alterations. Magnetic resonance imaging findings include white matter changes preferentially in the parieto-occipital regions. Although pathogenesis is not fully elucidated, vasoconstriction and brain hypoperfusion seem to be the cause of brain ischemia and vasogenic edema. Cerebrospinal fluid hypotension is also a reported plausible pathogenic mechanism. Case Description We present a case of PRES following laminectomy and fixation for L4-5 lumbar stenosis and spondylolisthesis. The patient presented with status epilepticus immediately after surgery that lasted 5 days. Brain magnetic resonance imaging showed fluid attenuated inversion recovery and T2 hyperintensities in the bilateral parietal and occipital lobes and external capsules. On the basis of postoperative lumbar images, we hypothesized that an unnoticed cerebrospinal fluid leak might have contributed to development of PRES. The patient developed multiple postoperative complications but ultimately recovered after treatment for severe hypertension and seizures. Conclusions Prompt recognition and treatment of this potentially life-threatening syndrome is necessary to increase the likelihood of favorable outcome. Spinal surgeons need to be aware of the possibility of neurologic deterioration after spinal surgery and be alert about the occurrence of a dural leak, either recognized or unnoticed, as the plausible mechanism triggering PRES.

Resumen Antecedentes El control cardiovascular y metabolico en pacientes que toman antipsicoticos es fundamental y adquiere una especial relevancia en la edad pediatrica, por ser pacientes mas vulnerables y porque cada vez se prescriben farmacos de este tipo en mas ocasiones. Objetivo Describir el grado de cumplimiento de las recomendaciones de control de parametros cardiovasculares y metabolicos en un grupo de ninos y jovenes en tratamiento antipsicotico. Metodo Se trata de un estudio descriptivo transversal en el que se comparan un grupo de 220 pacientes de 8-17 anos, diagnosticados de trastorno mental (TM) y en tratamiento antipsicotico, con otro grupo de referencia constituido por 199 individuos asmaticos no expuestos a antipsicoticos del mismo grupo de edad. Los datos se extrajeron de la historia clinica informatizada ECAP en el ano 2013. Resultados La edad de los ninos se situa entre los 8 y 17 anos. La media de edad es de 12 anos. La risperidona es el antipsicotico pautado mas frecuentemente (62,7%). El porcentaje de registro de peso, talla, indice de masa corporal (IMC) y presion arterial (PA) es de aproximadamente un 50% en los pacientes del grupo TM. En el grupo TM se observa un mayor registro de los parametros fisicos de control cardiovascular (peso, talla, IMC y PA) en comparacion con el grupo Asma. En conjunto, se registran mas los parametros fisicos que los parametros bioquimicos. Conclusiones Este estudio evidencia la necesidad de seguir insistiendo en la monitorizacion de los parametros cardiovasculares y metabolicos en los ninos y jovenes en tratamiento con antipsicoticos.

Background Cardiovascular and metabolic monitoring of patients on antipsychotic medication is essential. This becomes more important in those of paediatric age, as they are more vulnerable, and also because prescriptions of this kind of drugs are still increasing. Aim To evaluate the monitoring of cardiovascular and metabolic risk factors in a group of children and young people on antipsychotic medication. Method A descriptive cross-sectional study was conducted in which a group of 220 patients aged 8–17 years, diagnosed with a mental disorder and on antipsychotic treatment. They were compared to a control group of 199 asthmatic patients not exposed to antipsychotic drugs. Data was extracted from the computerized clinical history ECAP in 2013. Results The mean age of the children was 12 years (8–17). Risperidone (67%) was the most frequent treatment. The recording of body mass index (BMI) and blood pressure (AP) was 50% in Mental Disorder (MD) patients. A higher number of cardiovascular monitoring physical parameters (weight, height, BMI and BP) were observed in the MD group compared to the control Asthma control group. Altogether, more physical parameters than biochemistry parameters were recorded. Conclusions This study shows that the recording of cardiovascular parameters and metabolic studies needs to be improved in children and adolescents on treatment with antipsychotics.

The star-discrepancy is a quantitative measure for the irregularity of distribution of a point set in the unit cube that is intimately linked to the integration error of quasi-Monte Carlo algorithms. These popular integration rules are nowadays also applied to very high-dimensional integration problems. Hence multi-dimensional point sets of reasonable size with low discrepancy are badly needed. A seminal result from Heinrich, Novak, Wasilkowski and Woźniakowski shows the existence of a positive number C such that for every dimension d there exists an N -element point set in [0,1)d with star-discrepancy of at most C d ∕ N . This is a pure existence result and explicit constructions of such point sets would be very desirable. The proofs are based on random samples of N -element point sets which are difficult to realize for practical applications. In this paper we propose to use secure pseudorandom bit generators for the generation of point sets with star-discrepancy of order O ( d ∕ N ) . This proposal is supported theoretically and by means of numerical experiments.

Bacillus thuringiensis Cry2Ab toxin has been used in combination with Cry1Ac for resistance management on the Bt-cotton that is widely planted worldwide. However, little is known regarding Cry2Ab mode of action. Particularly, there is a gap of knowledge on the identification of insect midgut proteins that bind Cry2Ab and mediate toxicity. In the case of Cry1Ab toxin, a transmembrane cadherin protein and glycosyl-phosphatidylinositol (GPI) anchored proteins like aminopeptidase-N1 (APN1) or alkaline-phosphatase (ALP) from Manduca sexta, have been shown to be important for oligomer formation and insertion into the membrane. Binding competition experiments showed that Cry2Ab toxin does not share binding sites with Cry1Ab toxin in M. sexta brush border membrane vesicles (BBMV). Also, that Cry2Ab shows reduced binding to the Cry1Ab binding molecules cadherin, APN1 or ALP. Finally, ligand blot experiments and protein sequence by LC-MS/MS identified APN2 isoform as a Cry2Ab binding protein. Cloning and expression of APN2 confirmed that APN2 is a Cry2Ab binding protein.

Cerebral palsy (CP) describes a group of disorders affecting the development of movement and posture, causing activity limitation. Access to technology can alleviate some of these limitations. Many studies have used vision-based movement capture systems to overcome problems related to discomfort and fear of wearing devices. In contrast, there has been no research assessing the behavior of vision-based movement capture systems in people with involuntary movements. In this paper, we look at the potential of the Kinect sensor as an assistive technology for people with cerebral palsy. We developed a serious game, called KiSens Numeros, to study the behavior of Kinect in this context and eighteen subjects with cerebral palsy used it to complete a set of sessions. The results of the experiments show that Kinect filters some of peoples involuntary movements, confirming the potential of Kinect as an assistive technology for people with motor disabilities.

Bacillus thuringiensis Cry toxins are currently used for pest control in transgenic crops but evolution of resistance by the insect pests threatens the use of this technology. The Cry1AbMod toxin was engineered to lack the alpha helix-1 of the parental Cry1Ab toxin and was shown to counter resistance to Cry1Ab and Cry1Ac toxins in different insect species including the fall armyworm Spodoptera frugiperda . In addition, Cry1AbMod showed enhanced toxicity to Cry1Ab-susceptible S. frugiperda populations. To gain insights into the mechanisms of this Cry1AbMod-enhanced toxicity, we isolated the Cry1AbMod toxin binding proteins from S. frugiperda brush border membrane vesicles (BBMV), which were identified by pull-down assay and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The LC–MS/MS results indicated that Cry1AbMod toxin could bind to four classes of aminopeptidase (N1, N3, N4 y N5) and actin, with the highest amino acid sequence coverage acquired for APN 1 and APN4. In addition to these proteins, we found other proteins not previously described as Cry toxin binding proteins. This is the first report that suggests the interaction between Cry1AbMod and APN in S. frugiperda .

Cruciferous sprouts (e.g. broccoli and red radish) are rich source of health-promoting phytochemicals that are more concentrated than in the adult plant edible organs; however, these tiny microgreens need cold storage conditions to preserve their quality to reach the consumers in microbiologically safe conditions, maintaining their composition and acceptability. In this work, the microbiological status and phytochemical composition of broccoli and radish sprouts were evaluated at harvest (Day 0), and after seven and fourteen days of storage at 5 and 10 °C. Pathogenic microorganisms were absent during shelf-life; nevertheless, the slight growth of Enterobacteriaceae organisms, aerobic mesophilic and psychotropic bacteria, molds and yeasts was assessed. The storage temperature influenced the quality and content of bioactives in the sprouts, and for practical applications, storage at 5 °C is the most suitable option. Moreover, these fresh crucifers remain acceptable for consumers after 14 d storage period, being an interesting option for consuming fresh and naturally-functional foods.

A five-layered software architecture translating movements into mouse clicks has been developed and tested on an Arduino platform with two different sensors: accelerometer and flex sensor. The architecture comprises low-pass and derivative filters, an unsupervised classifier that adapts continuously to the strength of the user's movements and a finite state machine which sets up a timer to prevent involuntary movements from triggering false positives. Four people without disabilities and four people with cerebral palsy (CP) took part in the experiments. People without disabilities obtained an average of 100% and 99.3% in precision and true positive rate (TPR) respectively and there were no statistically significant differences among type of sensors and placement. In the same experiment, people with disabilities obtained 97.9% and 100% in precision and TPR respectively. However, these results worsened when subjects used the system to access a communication board, 89.6% and 94.8% respectively. With their usual method of access-an adapted switch- they obtained a precision and TPR of 86.7% and 97.8% respectively. For 3-out-of-4 participants with disabilities our system detected the movement faster than the switch. For subjects with CP, the accelerometer was the easiest to use because it is more sensitive to gross motor motion than the flex sensor which requires more complex movements. A final survey showed that 3-out-of-4 participants with disabilities would prefer to use this new technology instead of their traditional method of access.

Zrsr2 has been attributed a role in splice site recognition of U12 and U2 introns. To better understand the part played by minor splicing during oogenesis and early embryo development, we produced Zrsr2 mutant mice (Zrsr2mu). In Zrsr2mu female oogenesis was blocked at the secondary follicle stage, in a similar way as Zrsr1mu affects spermatogenesis. Zrsr2mu follicles showed altered expression of genes related to gonad development, DNA replication and cell cycle regulation, and altered splicing events involving enrichment of U12-type intron retention (IR). Embryo development was impaired during zygotic gene activation (ZGA) at the 2-cell stage when female Zrsr2mu were crossed with male Zrsr1mu. These embryos showed increased IR in U12-containing genes related to the cell cycle and mitotic nuclear division. Remarkably, both mouse Zrsr1 and Zrsr2 were required for conversion of mouse induced pluripotent stem cells (iPSC) into 2C-like cells. According to our results, Zrsr1 and Zrsr2 are essential during overall chromatin reorganization in the meiotic prophase of meiosis, ZGA and conversion of pluripotent into 2C-like cells.

Accelerator mass spectrometry and benzene synthesis coupled with liquid scintillation spectrometry are often used for accurate measurements of 14C activity in the environmental matrices. Thermal oxidation is one of the methods employed for 14C determination in environmental matrices. In this method, the sample is oxidised at high temperature (600–900 °C) to convert carbon species to CO2 and trapped in an amine-based absorber for determining the activity in a liquid scintillation counting (LSC) system. In this study, the performance of a commercially available tube furnace system (pyrolyser), for batch combustion of samples, was evaluated for the determination of 14C specific activity in terrestrial biota samples. Significant improvements over the manufacturer specified method, which is primarily designed for analysis of samples with activity well above the environmental background level, was implemented to achieve accurate determination of 14C specific activity at ambient background level. In the improved method, the CO2 produced from the combustion of the sample was isolated from the combustion products through cryogenic trapping and then absorbed in the absorber (Carbo-Sorb E) through a simple off-line transfer process. This allowed (i) optimisation of CO2 absorption by the absorber (2.2477 g of CO2/10 mL), (ii) achieving good accuracy and precision in the measurements, and a minimum detectable activity value of 13 Bq kg−1C for a counting time of 300 min (7 Bq kg−1C for 1000 min), (iii) avoiding uncertainty associated with the determination of recovery of 14C in the combustion and trapping process, and (iv) elimination of the need for an independent determination of carbon content (%) for expressing the results in terms of 14C specific activity. The method is capable of yielding accurate results with a deviation of, The authors would like to thank the Board of Research in Nuclear Science (BRNS, DAE, Govt. of India, for funding the research programme (BRNS sanction no. 2013/36/22-BRNS/3341 dated 18.03.2014). The authors would like to thank Shri. H. S. Kushwaha, Outstanding Scientist, BARC, Mumbai, and Dr. D Roy, Programme Officer, BRNS for their comments and suggestions. Thanks are due to Sri B N Dileep, Officer-in-charge, Environmental Survey Laboratory, and many officials and scientists of Kaiga Generating Station, Kaiga for extending logistical support for this study. Thanks are due to Dr Reshmi T.R and Dr Sudeesh, Isotope Hydrology Division, Centre for Water Resources Development and Management, Kozhikode, Kerala for isotope ratio measurements.

Qualitative and quantitative changes in gut microbiota play a very important role in cirrhosis. Humans harbour around 100 quintillion gut bacteria, thus representing around 10 times more microbial cells than eukaryotic ones. The gastrointestinal tract is the largest surface area in the body and it is subject to constant exposure to these living microorganisms. The existing symbiosis, proven by the lack of proinflammatory response against commensal bacteria, implies the presence of clearly defined communication lines that contribute to the maintenance of homeostasis of the host. Therefore, alterations of gut flora seem to play a role in the pathogenesis and progress of multiple liver and gastrointestinal diseases. This has made its selective modification into an area of high therapeutic interest. Bacterial translocation is defined as the migration of bacteria or bacterial products from the intestines to the mesenteric lymph nodes. It follows that alteration in gut microbiota have shown importance, at least to some extent, in the pathogenesis of several complications arising from terminal liver disease, such as hepatic encephalopathy, portal hypertension and spontaneous bacterial peritonitis. This review sums up, firstly, how liver disease can alter the common composition of gut microbiota, and secondly, how this alteration contributes to the development of complications in cirrhosis.

Qualitative and quantitative changes in gut microbiota play a very important role in cirrhosis. Humans harbour around 100 quintillion gut bacteria, thus representing around 10 times more microbial cells than eukaryotic ones. The gastrointestinal tract is the largest surface area in the body and it is subject to constant exposure to these living microorganisms. The existing symbiosis, proven by the lack of proinflammatory response against commensal bacteria, implies the presence of clearly defined communication lines that contribute to the maintenance of homeostasis of the host. Therefore, alterations of gut flora seem to play a role in the pathogenesis and progress of multiple liver and gastrointestinal diseases. This has made its selective modification into an area of high therapeutic interest. Bacterial translocation is defined as the migration of bacteria or bacterial products from the intestines to the mesenteric lymph nodes. It follows that alteration in gut microbiota have shown importance, at least to some extent, in the pathogenesis of several complications arising from terminal liver disease, such as hepatic encephalopathy, portal hypertension and spontaneous bacterial peritonitis. This review sums up, firstly, how liver disease can alter the common composition of gut microbiota, and secondly, how this alteration contributes to the development of complications in cirrhosis.

Pinostrobin is a flavanone isolated from Renealmia alpinia, a plant used in folk medicine to treat snakebites. We tested the inhibitory ability of pinostrobin on the enzymatic, anticoagulant, myotoxic and edema-inducing activities of a PLA2 isolated from Crotalus durissus cumanensis venom. The compound displayed IC50 values of 1.76mM and 1.85mM (95% Confidence intervals: 1.34-2.18 and 1.21-2.45) on the PLA2 enzymatic activity, when either aggregated or monodispersed substrates were used, respectively. When mice were injected with PLA2 preincubated with 0.4, 2.0 and 4.0mM of pinostrobin, myotoxic activity induced by the PLA2 was inhibited up to 87%. Nevertheless, these values decreased up to 56% when the pinostrobin was injected into muscle after PLA2. Pinostrobin inhibited edema-forming and anticoagulant activities of the PLA2. In order to have insights on the mode of action of pinostrobin, intrinsic fluorescence and ultraviolet studies were performed. Results suggest that pinostrobin interacts directly with the PLA2. These findings were supported by molecular docking results, which suggested that pinostrobin forms hydrogen bonds with residues His48 and Asp49 of PLA2, besides, a π-π stacking interactions with those of residues Phe5 and Trp31, and rings C of flavanone and Tyr52 of the toxin.

El perfeccionismo es un rasgo de la personalidad caracterizado por la imposición a uno mismo de unas normas de desempeño poco realistas, la motivación por ser perfeccionista y la percepción del entorno como demasiado exigente y crítico. Este estudio tuvo por objeto analizar la literatura científica sobre perfeccionismo en niños y adolescentes, publicada en 4 bases de datos (Web of Science, Scopus, PsycINFO y Education Resources Information Center), entre el año 2004 y el 2014. Se obtuvieron 325 documentos que fueron analizados con base en distintos indicadores bibliométricos, como el análisis de la producción temporal, las revistas y autores más productivos sobre el tópico y el índice de coautoría, así como un análisis y discusión de las características de la población, los principales instrumentos empleados y las temáticas identificadas. Se halló una tendencia a elaborar los trabajos en colaboración y un número considerable de grandes productores (Gordon L. Flett, Paul L. Hewitt, Andrew P. Hill y Bart Soenens). Destacaron la Frost Multidimensional Perfectionism Scale y la Child and Adolescent Perfectionism Scale como los 2 instrumentos más empleados para evaluar el perfeccionismo en niños y adolescentes. Igualmente, prevalecieron los estudios realizados en adolescentes frente a aquellos con participantes de población infantil. Se observó que la mayor parte de los documentos analizados se centraron en analizar la relación entre el perfeccionismo y la psicopatología. Por último, se discuten las temáticas identificadas, las limitaciones encontradas y los aspectos consolidados, sirviendo como referencia para la realización de futuros estudios sobre el campo del perfeccionismo durante la infancia y la adolescencia. Perfectionism is a personality trait characterized by the self-imposition of unrealistic standards of performance, the motivation to be a perfectionist and the perception of the environment as too demanding and critical. The aim of this study was to analyze the scientific literature on perfectionism in children and adolescents. The documents were collected from 4 databases (Web of Science, Scopus, PsycINFO and Education Resources Information Center), limiting the period between 2004 and 2014. These 325 documents were analyzed with different bibliometric indicators such as the analysis of the temporal productivity, the most productive journals and authors, and the co-authored index, as well as an examination and discussion of the population characteristic, the main instruments used, and the issues identified. It was found a tendency to develop collaborative work and a considerable number of big producers (Gordon L. Flett, Paul L. Hewitt, Andrew P. Hill y Bart Soenens). The Frost Multidimensional Perfectionism Scale and the Child and Adolescent Perfectionism Scale were the most used instruments to assess perfectionism in children and adolescents. Likewise, there were more studies in adolescents than in children. It was observed that most of the documents analyzed focused on examine the relationship between perfectionism and psychopathology. Finally, the main identified issues are discussed, found limitations and consolidated areas, serving as a reference for future studies on the field of perfectionism during childhood and adolescence. Parte de esta investigación está subvencionada por la ayuda para la contratación de personal investigador en formación predoctoral, Programa VALi + d, concedida a María Vicent, y el proyecto «Evaluación de la ansiedad escolar y su relación con variables psicoeducativas en la infancia. Estudio de la eficacia de un programa preventivo» (EDU2012-35124), cuyo IP es el doctor José Manuel García Fernández.

Resumen Introduccion Los accidentes cerebrovasculares representan la tercera causa de muerte en la edad adulta. Hay pocas investigaciones que afirmen que existen factores de riesgo que afectan al pronostico funcional tras un ictus. De los trabajos que analizan estos factores de riesgo, pocos valoran la obesidad. Objetivo Conocer posibles factores que afectan al pronostico de los pacientes tras un ictus. Material y metodos Estudio epidemiologico observacional prospectivo analitico de los sujetos ingresados en la Unidad de Ictus del Hospital de Albacete durante 2 anos. La muestra fue dividida segun la puntuacion en la Escala de Rankin modificada a los 3 meses: buen o mal pronostico; esta puntuacion fue comparada mediante un analisis estadistico bivariante con las restantes variables: edad, sexo, hipertension arterial, diabetes mellitus, dislipidemia, obesidad (medida por circunferencia abdominal), tabaquismo y puntuacion al ingreso en las National Institute of Health Stroke Scale y Escala Neurologica Canadiense. Resultados Muestra final: 332 sujetos (207 hombres y 125 mujeres); edad media 70,14 (DT 11,71) anos. Circunferencia abdominal media: 104,57 (DT 14,55) cm; factores de riesgo mas prevalentes: hipertension, con 232 casos (70,3%), y diabetes, con 121 (36,7%). Se encontro relacion estadisticamente significativa entre el pronostico funcional tras un ictus y edad, sexo, circunferencia abdominal y escalas National Institute of Health Stroke y Canadiense. Conclusion Una circunferencia abdominal elevada se asocia a un peor pronostico tras un ictus. Esto refuerza la importancia de establecer politicas poblacionales contra este factor, extendido en nuestra sociedad. Igualmente, debe valorarse si puede ser un tratamiento para la recuperacion tras el ictus.

Background & Aims Patients with cirrhosis show recurrent access of bacterial products into the bloodstream inducing a multi-altered immunological status leading to relevant complications. We aimed at evaluating Bifidobacterium pseudocatenulatum CECT7765 effect on the host's macrophage function. Patients & methods Patients with cirrhosis and ascites were included. Granulocyte-macrophage colony-stimulating factor (GM-CSF) monocyte-derived and ascitic fluid (AF) macrophages were cultured with M-CSF, lipopolysaccharide (LPS) and/or the bifidobacterial strain. Pellets and supernatants were evaluated for gene expression of M1 and M2-related genes and cytokine secretion. Cell surface expression molecules were evaluated by flow cytometry. Kupffer cells from bile duct ligated and CCl 4 rats were also evaluated. Results Experiments were run on GM-CSF blood-derived and AF macrophages from 10 patients with cirrhosis and 10 healthy donors. Different macrophage morphology was observed by optical microscopy in cells stimulated with bifidobacteria vs. LPS. M2-like expression of CD206, CD163 and CD16 was significantly increased in macrophages after stimulation with the bifidobacterial strain vs. LPS. B. pseudocatenulatum CECT7765 was able to significantly change the cytokine secretion pattern of blood-derived and AF macrophages and Kupffer cells from bile duct ligated and CCl 4 cirrhotic rats compared to that induced by LPS. B. pseudocatenulatum CECT7765 was also effective in inducing a phenotype transition and a functional change from an M1- to an M2-related gene expression and cytokine secretion pattern in AF macrophages even after LPS-pretreatment. B. pseudocatenulatum CECT7765 did not reduce AF macrophage bacterial killing capacity. Conclusion B. pseudocatenulatum CECT7765 induces a morphologic, phenotypic and functional transition towards an anti-inflammatory profile in GM-CSF monocyte-derived and AF macrophages from patients with cirrhosis that may help in controlling sustained inflammation in decompensated cirrhosis.

Resumen Objetivos El objetivo fue evaluar la evidencia disponible sobre la validez, precision diagnostica y utilidad clinica del test multidiana de ADN en heces (Cologuard™) en el cribado de cancer colorrectal (CCR). Material y metodos Se realizo una revision sistematica consultando MedLine, EMBASE y Web of Science hasta julio de 2014. Se seleccionaron estudios de pruebas diagnosticas que evaluaran el test en adultos asintomaticos sometidos a cribado de CCR. La calidad y el riesgo de sesgo se evaluaron mediante la herramienta Quality Assessment of Diagnostic Accuracy Studies. El nivel de evidencia se definio segun The National Institute for Healthand Clinical Excellence. Se realizo una sintesis cualitativa. Resultados Se identificaron 299 referencias bibliograficas, incluyendose un informe de sintesis y cinco estudios de pruebas diagnosticas, tres de ellos con diseno caso-control en fase II de Sackett y de moderada calidad, y dos con diseno prospectivo en fase III de Sacket y de alta calidad. La sensibilidad para detectar CCR fue superior al 90%, pero solo del 40% para la deteccion de adenoma avanzado. El test proporciono evidencia diagnostica concluyente para descartar CCR (cociente de probabilidad negativo, CPN: 0,02-0,09), aunque no fue util para descartar adenoma avanzado (CPN: 0,5-0,7). Conclusiones El test Cologuard™ es una prueba de cribado valida para descartar lesiones cancerosas, resultando suboptima para descartar lesiones precancerosas. No hay evidencia sobre resultados en terminos de mortalidad o supervivencia, ni sobre coste-efectividad.

Objectives The aim of this study was to assess the available evidence on the validity, diagnostic accuracy and clinical utility of the multitarget DNA test in feces (Cologuard™) for screening for colorectal cancer (CRC). Material and methods A systematic review was performed by consulting MedLine, EMBASE and Web of Science to July 2014. Studies on diagnostic tests were selected that evaluated the test in asymptomatic adults who underwent CRC screening. The quality and risk of bias were assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. The level of evidence was defined according to the National Institute for Health and Clinical Excellence. A qualitative synthesis was conducted. Results A total of 299 literature references were identified, including 1 synthesis report and 5 diagnostic test studies. Three of the five studies had a case-control design in Sackett phase II and were of moderate quality, and two had a prospective design in Sacket phase III and were of high quality. The sensitivity for detecting CRC was greater than 90%, but only 40% for detecting advanced adenomas. The test provided conclusive diagnostic evidence to rule out CRC (negative likelihood ratio, LR−: 0.02–0.09), although it was not useful for ruling out advanced adenoma (LR−: 0.5–0.7). Conclusions The Cologuard™ test is a valid screening test for ruling out cancerous lesions but is suboptimal for ruling out precancerous lesions. There is no evidence in terms of mortality, survival or cost-effectiveness.

Human adenoviruses (HAdV) are the cause of many acute infections, mostly in the respiratory and gastrointestinal (GI) tracts, as well as conjunctivitis. HAdV diseases in immunocompetent individuals are mostly self-limiting; however, in immunocompromised individuals, especially in pediatric units, HAdV infections are the cause of high morbidity and mortality. Despite the significant clinical impact, there are currently no approved antiviral therapies for HAdV infections. Here, we provide an overview of the different targets that could be considered for the design of specific drugs against HAdV, as well as the available in vitro and in vivo tools for the screening and evaluation of candidate molecules.

This study examines total Hg, free Hg(0), matrix-bound Hg and MeHg contents in soils and plant tissues from two old cinnabar mining sites (La Soterrana and Los Rueldos) in Asturias (Spain), as well as Hg transfer and translocation from soils to plants. The studied soils from both mines accumulated moderate to very high total Hg concentrations (36–1709 mg·kg− 1) but quite low available Hg contents (0.005–3.062 mg·kg− 1) which resulted in relatively low transfer factor values. Matrix-bound Hg was the prevalent Hg form in soils from both mining sites representing 67–88% of total Hg content. Significant Hg(0) concentrations were found in soils as a consequence of atmospheric deposition. Appreciable MeHg concentrations were found in soils from La Soterrana mining site while non-detectable MeHg could be found in soils from Los Rueldos. All the studied plants can be considered as excluders. Hg(0) is practically absent in roots indicating that this Hg form is not uptaken from soils. Hg(0) contents found in aboveground tissues evidenced that foliar uptake of atmospheric Hg occurs. Significant MeHg contents were found in the aerial parts for all studied plants. However, MeHg contents in roots were extremely low in La Soterrana plants and non-detectable in those from Los Rueldos.

Resumen Objetivo Estimar y comparar la validez diagnostica de la tomosintesis y la mamografia digital para cribar y diagnosticar el cancer de mama. Material y metodos Realizamos una revision sistematica consultando MedLine, EMBASE y Web of Science en el periodo de junio de 2010 a febrero de 2013. Los terminos de busqueda fueron: cancer de mama, cribado, tomosintesis, mamografia, sensibilidad y especificidad. Se incluyeron estudios de pruebas diagnosticas y revisiones sistematicas. Dos investigadores hicieron la seleccion y evaluacion. Usamos QUADAS 2 para valorar el riesgo de sesgo y los criterios NICE para el nivel de evidencia. Se hizo una sintesis narrativa. Resultados De los 151 estudios originales identificados se seleccionaron 11 que incluyeron 2.475 mujeres. Su calidad fue baja, con riesgo de sesgo de seleccion y seguimiento, y limitaciones para aplicar sus resultados. Su nivel de evidencia no fue superior a II . La sensibilidad de la tomosintesis oscilo entre el 69 y el 100% y la especificidad entre el 54 y el 100%. El cociente de probabilidad negativo fue bueno, lo que la convertiria en una prueba de confirmacion diagnostica. La tomosintesis con una proyeccion no fue superior a la mamografia digital con 2, y con 2 proyecciones los resultados no fueron concluyentes. Conclusiones Los resultados de la validez diagnostica de la tomosintesis en el diagnostico del cancer de mama no fueron concluyentes, y no los hubo para usarla en el cribado.

Objective To estimate and compare the diagnostic validity of tomosynthesis and digital mammography for screening and diagnosing breast cancer. Material and methods We systematically searched MedLine, EMBASE, and Web of Science for the terms breast cancer, screening, tomosynthesis, mammography, sensitivity, and specificity in publications in the period comprising June 2010 through February 2013. We included studies on diagnostic tests and systematic reviews. Two reviewers selected and evaluated the articles. We used QUADAS 2 to evaluate the risk of bias and the NICE criteria to determine the level of evidence. We compiled a narrative synthesis. Results Of the 151 original studies identified, we selected 11 that included a total of 2475 women. The overall quality was low, with a risk of bias and follow-up and limitations regarding the applicability of the results. The level of evidence was not greater than level II. The sensitivity of tomosynthesis ranged from 69% to 100% and the specificity ranged from 54% to 100%. The negative likelihood ratio was good, and this makes tomosynthesis useful as a test to confirm a diagnosis. One-view tomosynthesis was no better than two-view digital mammography, and the evidence for the superiority of two-view tomosynthesis was inconclusive. Conclusions The results for the diagnostic validity of tomosynthesis in the diagnosis of breast cancer were inconclusive and there were no results for its use in screening.

Resumen Objetivo Conocer la incidencia de complicaciones asociadas a los cateteres venosos centrales (tunelizados, reservorios y PICC), en pacientes con patologia oncohematologica, ingresados en Unidades de Hematologia o Trasplantes de Progenitores Hematopoyeticos, en dos hospitales terciarios. Metodologia Se desarrollo un estudio descriptivo transversal donde se recogieron datos sociodemograficos, clinicos, complicaciones y seguimiento del protocolo de cuidados. A cada cateter se le asigno un numero de identificacion correlativo. Se recogio informacion de 366 cateteres: 185 en el Hospital Universitario Ramon y Cajal (HURYC): 80 tunelizados, 40 reservorios y 65 PICC; 181 en el Hospital Universitario Gregorio Maranon (HUGM): 101 tunelizados y 80 reservorios. Resultados Las principales complicaciones en los tunelizados fueron las infecciones (13,7% en el HURYC vs. 6,8% en el HUGM; p Conclusiones La diferencia entre hospitales respecto a la infeccion y oclusion, puede asociarse a las distintas pautas de cuidados. Destaca la alta incidencia de flebitis y trombosis en PICC.

Bacillus thuringiensis Cry toxins exert their toxic effect by specific recognition of larval midgut proteins leading to oligomerization of the toxin, membrane insertion and pore formation. The exposed domain II loop regions of Cry toxins have been shown to be involved in receptor binding. Insect cadherins have shown to be functionally involved in toxin binding facilitating toxin oligomerization. Here, we isolated a VHH (VHHA5) antibody by phage display that binds Cry3Aa loop 1 and competed with the binding of Cry3Aa to Tenebrio molitor brush border membranes. VHHA5 also competed with the binding of Cry3Aa to a cadherin fragment (CR12) that was previously shown to be involved in binding and toxicity of Cry3Aa, indicating that Cry3Aa binds CR12 through domain II loop 1. Moreover, we show that a loop 1 mutant, previously characterized to have increased toxicity to T. molitor, displayed a correlative enhanced binding affinity to T. molitor CR12 and to VHHA5. These results show that Cry3Aa domain II loop 1 is a binding site of CR12 T. molitor cadherin.

Four methods for acid digestion of seaweeds were compared in 10 commercially available seaweeds: (i) in stainless steel-Teflon®PTFE-bombs at high pressure and temperature, (ii) in closed-Teflon®PFA-vessels at high pressure and temperature, (iii) in open-polypropylene-tubes with reflux caps in a graphite heating block at high temperature and (iv) in closed-TFM™PTFE-vessels with microwave-assisted controlled pressure and temperature. Hg was determined in all digests by cold vapour atomic fluorescence spectrometry (CV-AFS). Assessment of digestion methods was performed by comparison with the results obtained for total mercury determination by the Method EPA 7473, based on direct mercury analysis in the solid samples, and with a reference material BCR-279. The open vessel digestion system with reflux in a graphite heating block at high temperature constitutes the best choice since it was found to give the better Hg extraction (83-103%) as well as the lowest variability, being RSD

Background & Aims Bacterial endotoxin is present in patients with advanced cirrhosis and can induce an immunogenic response without an overt infection. Norfloxacin is a gram-negative bactericidal drug able to maintain low endotoxin levels and stimulate IL-10 production. We aimed at investigating the role of IL-10 in decreasing endotoxin absorption in cirrhotic mice treated with norfloxacin. Methods Cirrhosis was induced by carbon tetrachloride or bile duct ligation in wild type and IL10-deficient mice with or without norfloxacin prior to an intragastrical administration of E. coli, K. pneumonia or E. faecalis . Spontaneous and induced bacterial translocation, free endotoxin and cytokine levels were evaluated in mesenteric lymph nodes. Intestinal permeability was followed by fluorimetry and barrier integrity markers were measured in disrupted intestinal samples. The inflammatory-modulating mechanism was characterized in purified intestinal mononuclear cells. Results Norfloxacin reduced spontaneous and induced MLN positive-cultures in wild type and IL-10 -deficient animals. However, reduction of free endotoxin levels was associated with norfloxacin in wild type but not in IL-10 -deficient mice. Wild type but not IL-10 -deficient mice treated with norfloxacin significantly normalized intestinal permeability and improved gut barrier integrity markers. The toll-like receptor 4-mediated pro-inflammatory milieu was modulated by norfloxacin in a concentration-dependent manner in cultured intestinal mononuclear cells of wild type mice but not of IL-10 -deficient mice. The restoration of IL-10 levels in IL-10 -deficient animals reactivated the norfloxacin effect on inflammatory-modulation, gut barrier permeability, and luminal endotoxin absorption. Conclusion Norfloxacin not only reduces gram-negative intestinal flora but also participates in an IL-10-driven modulation of gut barrier permeability, thus reducing luminal free endotoxin absorption in experimental cirrhosis.

Reading comprehension skills have been linked to working memory's executive processes such as semantic updating, connecting and integrating information, and inhibition. Different studies have demonstrated that children who score poorly on working memory measures typically perform below expected standards across different academic areas. The aim of this paper is focused on the relationship of executive functions of WM and fluid intelligence with reading comprehension, and their common ability to predict academic achievement in a group of 77 third-grade primary students. As predicted, there was a very clear pattern of positive and significant correlations. Cognitive variables, such as WM's executive processes (particularly semantic updating) and fluid intelligence, correlated with reading variables and two academic measures of language and mathematics. Regression analyses showed that these higher cognitive variables predicted reading comprehension. Likewise, executive processes and reading comprehension, contributed independently to explain a relevant amount of the variance in academic achievement measures.

Renealmia alpinia (R. alpinia) typically occurs in the tropical rainforests of Mexico to Peru, Brazil through the Antilles, Guyana, Suriname, Colombia and Venezuela. It has traditionally been used against snakebite in Colombia. In addition to the common local use for pain, R. alpinia has been used as an antipyretic and antiemetic to treat wounds, malignant ulcers, epilepsy and fungal infections. The species of the Zingiberaceae family are famous for their use as spices and herbs. This review provides information on the traditional use of plants in the Zingiberaceae family, Renealmia genus, and specifically R. alpinia. We conducted a narrative review in English and Spanish in electronic databases, such as ScienceDirect, Napralert, PubMed, ScFinder, SciElo, during August 2011 to March 2013. We were interested in their applications in ethnomedicine and their chemical components, providing a major and methodical revision. We found 120 sources, 98 of which were selected as they contained essential information. This study has stimulated the development of a new work, which aims to isolate and evaluate metabolites from R. alpinia leads toward the development of a phytotherapeutic product, which might be accessible to the population. Studies on the toxicity and safety of R. alpinia are insufficient to provide information on the ethnomedical use of this species. Thus, the present review summarizes information about R. alpinia and proposes possible scope of future research to fill gaps identified in this narrative review. COL0014476