Cumplimiento, conocimiento y automedicación como factores asociados a los resultados clínicos negativos de la farmacoterapia

The patient plays a fundamental role in the attainment of good results in pharmacotherapy. Noncompliance,self-medication, or insufficient knowledge of the therapy being employed may provide asource for the causes of these negative clinical outcomes, otherwise known as medicine related problems(MRP). he Dader method was used in the evaluation, identification and classification of MRP. Theassociation of variables was established through the statistical Chi square test. Patient knowledge of themedicine, degree of compliance to therapy and self-medication were studied as causes of the negativeoutcomes encountered. 2556 patients were interviewed throughout the year that the study took place,giving a total of 2261 of valid cases. 33% presented an MRP as the cause of his/her visit to the hospitalemergency ward. Knowledge of the medicine, compliance and self-medication were only studied in thepopulation that presented an MRP and in this work it is demonstrated that these are aspects that areassociated with different dimensions of MRP. It is not possible to establish an association between theexistence or not of negative clinical outcomes in patients with the factors of knowledge of medication,compliance and self-medication. This is due to the fact that these variables are not attributable to thepatient himself, but rather are associated with the characteristics of each medicine.El paciente juega un papel primordial en la consecución de los resultados terapéuticos. El incumplimiento,la automedicación, o la falta de conocimiento del la farmacoterapia pueden ser causas de esosresultados clínicos negativos, denominados en ocasiones problemas relacionados con medicamentos(PRM). El método Dáder se utilizó para la evaluación, identificación y clasificación de PRM. Laasociación de variables se estableció mediante el estadístico chi cuadrado. El conocimiento de la medicación,el cumplimiento y la automedicación fueron estudiados como causa de estos resultados negativosde la medicación. Fueron entrevistados 2556 pacientes durante el año de estudio, resultando 2261 casosválidos. El 33 % presentaron un PRM como causa de visita a urgencias. El conocimiento de la medicación,el cumplimiento y la automedicación fueron estudiados solo en la población que presentó unPRM y se demuestra que son aspectos asociados a las distintas dimensiones de PRM. No es posibleestablecer asociación entre la existencia o no de resultados clínicos negativos en los pacientes con elconocimiento de la medicación, el cumplimiento y la automedicación, debido a que estas variables noson atributos del paciente sino que están asociadas a cada medicamento

Decoding machine learning benchmarks

Despite the availability of benchmark machine learning (ML) repositories (e.g., UCI, OpenML), there is no standard evaluation strategy yet capable of pointing out which is the best set of datasets to serve as gold standard to test different ML algorithms. In recent studies, Item Response Theory (IRT) has emerged as a new approach to elucidate what should be a good ML benchmark. This work applied IRT to explore the well-known OpenML-CC18 benchmark to identify how suitable it is on the evaluation of classifiers. Several classifiers ranging from classical to ensembles ones were evaluated using IRT models, which could simultaneously estimate dataset difficulty and classifiers' ability. The Glicko-2 rating system was applied on the top of IRT to summarize the innate ability and aptitude of classifiers. It was observed that not all datasets from OpenML-CC18 are really useful to evaluate classifiers. Most datasets evaluated in this work (84%) contain easy instances in general (e.g., around 10% of difficult instances only). Also, 80% of the instances in half of this benchmark are very discriminating ones, which can be of great use for pairwise algorithm comparison, but not useful to push classifiers abilities. This paper presents this new evaluation methodology based on IRT as well as the tool decodIRT, developed to guide IRT estimation over ML benchmarks.Comment: Paper published at the BRACIS 2020 conference, 15 pages, 4 figure

Localization of a bacterial group II intron-encoded protein in human cells

Group II introns are mobile retroelements that self-splice from precursor RNAs to form ribonucleoparticles (RNP), which can invade new specific genomic DNA sites. This specificity can be reprogrammed, for insertion into any desired DNA site, making these introns useful tools for bacterial genetic engineering. However, previous studies have suggested that these elements may function inefficiently in eukaryotes. We investigated the subcellular distribution, in cultured human cells, of the protein encoded by the group II intron RmInt1 (IEP) and several mutants. We created fusions with yellow fluorescent protein (YFP) and with a FLAG epitope. We found that the IEP was localized in the nucleus and nucleolus of the cells. Remarkably, it also accumulated at the periphery of the nuclear matrix. We were also able to identify spliced lariat intron RNA, which co-immunoprecipitated with the IEP, suggesting that functional RmInt1 RNPs can be assembled in cultured human cells.This work was supported by research grants CSD 2009–0006 from the Consolider-Ingenio, BIO2011-24401 and BIO2014-51953-P from the Spanish Ministerio de Economía y Competitividad all including ERDF (European Regional Development Funds). We thank Dr. Antonio Barrientos Durán for technical advice. MRC was supported by an FPI Ph.D grant. J.L.G.P´s laboratory is supported by CICE-FEDER-P09-CTS-4980, CICE-FEDER-P12-CTS-2256, Plan Nacional de I+D+I 2008–2011 and 2013–2016 (FIS-FEDER-PI11/01489 and FIS-FEDER-PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European Research Council (ERC-Consolidator ERC-STG-2012-233764) and by an International Early Career Scientist grant from the Howard Hughes Medical Institute (IECS-55007420).Peer Reviewe

Persistent drying in the tropics linked to natural forcing.

Approximately half of the world's population lives in the tropics, and future changes in the hydrological cycle will impact not just the freshwater supplies but also energy production in areas dependent upon hydroelectric power. It is vital that we understand the mechanisms/processes that affect tropical precipitation and the eventual surface hydrological response to better assess projected future regional precipitation trends and variability. Paleo-climate proxies are well suited for this purpose as they provide long time series that pre-date and complement the present, often short instrumental observations. Here we present paleo-precipitation data from a speleothem located in Mesoamerica that reveal large multi-decadal declines in regional precipitation, whose onset coincides with clusters of large volcanic eruptions during the nineteenth and twentieth centuries. This reconstruction provides new independent evidence of long-lasting volcanic effects on climate and elucidates key aspects of the causal chain of physical processes determining the tropical climate response to global radiative forcing.A.W. thanks the Swiss Federal Institute of Technology both for hosting his sabbatical and for the analysis of the stable isotopes. A.W. also thanks Cluster of Excellence CliSAP at the University of Hamburg for sponsoring collaboration. Collection of GU-Xi-1 by T.M. was supported through a sabbatical granted by the University of Puerto Rico (Mayagu¨ez) and the National Geographic Society Grant no. 3089-85 to T.M. partially supported survey of the cave and location of the stalagmite. The research was supported in part by the National Science Foundation ATM-1003502. Y.K. was also supported by grant NA10OAR4310137 from the National Oceanic and Atmospheric Administration— Climate Program Office. S.F.M.B. acknowledges financial support from the Schweizer National Fond Project CRS122 132646/1. D.B. was supported by National Science Foundation Grant ATM-1003219. G.L. acknowledges support from Helmholtz through PACES and REKLIM. We acknowledge the World Climate Research Program Working Group on Coupled Modeling, which is responsible for CMIP, and we thank the climate modelling groups for producing and making available their model output. Paul Sammarco (LUMCON) is thanked for some advice regarding statistical and data interpretation. This paper is a Lamont Doherty Contribution number 7901. LB was supported by the French National Research Agency under EL PASO grant 10-Blan-608-01.This is the accepted manuscript. The final version is available at http://www.nature.com/ncomms/2015/150714/ncomms8627/full/ncomms8627.html

The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

Exon sequence requirements for excision in vivo of the bacterial group II intron RmInt1

<p>Abstract</p> <p>Background</p> <p>Group II intron splicing proceeds through two sequential transesterification reactions in which the 5' and 3'-exons are joined together and the lariat intron is released. The intron-encoded protein (IEP) assists the splicing of the intron <it>in vivo </it>and remains bound to the excised intron lariat RNA in a ribonucleoprotein particle (RNP) that promotes intron mobility. Exon recognition occurs through base-pairing interactions between two guide sequences on the ribozyme domain dI known as EBS1 and EBS2 and two stretches of sequence known as IBS1 and IBS2 on the 5' exon, whereas the 3' exon is recognized through interaction with the sequence immediately upstream from EBS1 [(δ-δ' interaction (subgroup IIA)] or with a nucleotide [(EBS3-IBS3 interaction (subgroup IIB and IIC))] located in the coordination-loop of dI. The δ nucleotide is involved in base pairing with another intron residue (δ') in subgroup IIB introns and this interaction facilitates base pairing between the 5' exon and the intron.</p> <p>Results</p> <p>In this study, we investigated nucleotide requirements in the distal 5'- and 3' exon regions, EBS-IBS interactions and δ-δ' pairing for excision of the group IIB intron RmInt1 <it>in vivo</it>. We found that the EBS1-IBS1 interaction was required and sufficient for RmInt1 excision. In addition, we provide evidence for the occurrence of canonical δ-δ' pairing and its importance for the intron excision <it>in vivo.</it></p> <p>Conclusions</p> <p>The excision <it>in vivo </it>of the RmInt1 intron is a favored process, with very few constraints for sequence recognition in both the 5' and 3'-exons. Our results contribute to understand how group II introns spread in nature, and might facilitate the use of RmInt1 in gene targeting.</p

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography

Capsaicin Nanoparticles as Therapeutic Agents against Gliomas

Capsaicin is an alkaloid molecule with outstanding biological activity. Several reports have shown that capsaicin exerts significant antitumoral effects in several cancer cell lines, including gliomas. However, its application has been very limited due to its hydrophobicity, low affinity, and short life span. Gliomas are a heterogeneous group of brain malignant tumors with increasing prevalence worldwide. Standard therapy against these tumors generally includes resection by surgery, radiation, and chemotherapy or their combination. However, elicitation of tumor resistance to chemical or radiation treatments remains one of the main challenges to be resolved, particularly in the case of glioblastomas. Nanotechnology is an innovative approach to the treatment of Central Nervous System diseases and especially to gliomas treatment. Indeed, the use of nanotherapeutic formulations offers several advantages over the conventional methods of drug delivery therapy. In this review, we analyzed the current literature regarding the development of capsaicin-loaded nanoparticles as a promising approach for the treatment of malignant brain tumors

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel