Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared with Common ß-Chain Cytokines IL-5 and GM-CSF.

Despite recent advances in asthma management with anti-IL-5 therapies, many patients have eosinophilic asthma that remains poorly controlled. IL-3 shares a common ß subunit receptor with both IL-5 and GM-CSF but, through α-subunit-specific properties, uniquely influences eosinophil biology and may serve as a potential therapeutic target. We aimed to globally characterize the transcriptomic profiles of GM-CSF, IL-3, and IL-5 stimulation on human circulating eosinophils and identify differences in gene expression using advanced statistical modeling. Human eosinophils were isolated from the peripheral blood of healthy volunteers and stimulated with either GM-CSF, IL-3, or IL-5 for 48 h. RNA was then extracted and bulk sequencing performed. DESeq analysis identified differentially expressed genes and weighted gene coexpression network analysis independently defined modules of genes that are highly coexpressed. GM-CSF, IL-3, and IL-5 commonly upregulated 252 genes and downregulated 553 genes, producing a proinflammatory and survival phenotype that was predominantly mediated through TWEAK signaling. IL-3 stimulation yielded the most numbers of differentially expressed genes that were also highly coexpressed (n = 119). These genes were enriched in pathways involving JAK/STAT signaling. GM-CSF and IL-5 stimulation demonstrated redundancy in eosinophil gene expression. In conclusion, IL-3 produces a distinct eosinophil gene expression program among the ß-chain receptor cytokines. IL-3-upregulated genes may provide a foundation for research into therapeutics for patients with eosinophilic asthma who do not respond to anti-IL-5 therapies.

Potent benzoazepinone γ-secretase modulators with improved bioavailability.

The triazolyl amide γ-secretase modulators are potent alternatives to the cinnamyl amides that have entered the clinic for the treatment of Alzheimer's disease. Herein we build on the lead benzoazepinones described in our prior communication with imidazomethoxyarene moiety alternatives that offer opportunities to fine tune physical properties as well as address hERG binding and PK. Both half-life and bioavailability were significantly improved, especially in dog, with robust brain Aß42 lowering maintained in both transgenic mouse and rat.

Discovery of novel triazolobenzazepinones as γ-secretase modulators with central Aß42 lowering in rodents and rhesus monkeys.

Synthesis and SAR studies of novel triazolobenzazepinones as gamma secretase modulators (GSMs) are presented in this communication. Starting from our azepinone leads, optimization studies toward improving central lowering of Aß42 led to the discovery of novel benzo-fused azepinones. Several benzazepinones were profiled in vivo and found to lower brain Aß42 levels in Sprague Dawley rats and transgenic APP-YAC mice in a dose-dependent manner after a single oral dose. Compound 34 was further progressed into a pilot study in our cisterna-magna-ported rhesus monkey model, where we observed robust lowering of CSF Aß42 levels.

Lead optimization of 4,4-biaryl piperidine amides as γ-secretase inhibitors.

Alzheimer's disease is a major unmet medical need with pathology characterized by extracellular proteinaceous plaques comprised primarily of ß-amyloid. γ-Secretase is a critical enzyme in the cellular pathway responsible for the formation of a range of ß-amyloid peptides; one of which, Aß42, is believed to be responsible for the neuropathological features of the disease. Herein, we report 4,4 disubstituted piperidine γ-secretase inhibitors that were optimized for in vitro cellular potency and pharmacokinetic properties in vivo. Key agents were further characterized for their ability to lower cerebral Aß42 production in an APP-YAC mouse model. This structural series generally suffered from sub-optimal pharmacokinetics but hypothesis driven lead optimization enabled the discovery of γ-secretase inhibitors capable of lowering cerebral Aß42 production in mice.

Automated Pain Assessment in Children Using Electrodermal Activity and Video Data Fusion via Machine Learning.

OBJECTIVE: Pain assessment in children continues to challenge clinicians and researchers, as subjective experiences of pain require inference through observable behaviors, both involuntary and deliberate. The presented approach supplements the subjective self-report-based method by fusing electrodermal activity (EDA) recordings with video facial expressions to develop an objective pain assessment metric. Such an approach is specifically important for assessing pain in children who are not capable of providing accurate self-pain reports, requiring nonverbal pain assessment. We demonstrate the performance of our approach using data recorded from children in post-operative recovery following laparoscopic appendectomy. We examined separately and combined the usefulness of EDA and video facial expression data as predictors of children's self-reports of pain following surgery through recovery. Findings indicate that EDA and facial expression data independently provide above chance sensitivities and specificities, but their fusion for classifying clinically significant pain vs. clinically nonsignificant pain achieved substantial improvement, yielding 90.91% accuracy, with 100% sensitivity and 81.82% specificity. The multimodal measures capitalize upon different features of the complex pain response. Thus, this paper presents both evidence for the utility of a weighted maximum likelihood algorithm as a novel feature selection method for EDA and video facial expression data and an accurate and objective automated classification algorithm capable ofdiscriminating clinically significant pain from clinically nonsignificant pain in children.

Triazoles as γ-secretase modulators.

Synthesis, SAR, and evaluation of aryl triazoles as novel gamma secretase modulators (GSMs) are presented in this communication. Starting from the literature and in-house leads, we evaluated a range of five-membered heterocycles as replacements for olefins commonly found in non-acid GSMs. 1,2,3-C-aryl-triazoles were identified as suitable replacements which exhibited good modulation of γ-secretase activity, excellent pharmacokinetics and good central lowering of Aß42 in Sprague-Dawley rats.

Youth and Parent Appraisals of Participation in a Study of Spontaneous and Induced Pediatric Clinical Pain.

The current study examined youths' and their parents' perceptions concerning participation in an investigation of spontaneous and induced pain during recovery from laparoscopic appendectomy. Youth (age range 5-17 years) and their parents independently completed surveys about their study participation. On a 0 (very negative) -to-10 (very positive) scale, both parents 9.4(1.3) [mean(SD)] and youth 7.9(2.4) rated their experience as positive. Among youth, experience ratings did not differ by pain severity and survey responses did not differ by age. Most youth (83%) reported they would tell another youth to participate. Ethical issues regarding instigation of pain in youth for research purposes are examined.

Role of specific cytochrome P450 isoforms in the conversion of phenoxypropoxybiguanide analogs in human liver microsomes to potent antimalarial dihydrotriazines.

Phenoxypropoxybiguanides, such as PS-15, are antimalarial prodrugs analogous to the relationship of proguanil and its active metabolite cycloguanil. Unlike cycloguanil, however, WR99210, the active metabolite of PS-15, has retained in vitro potency against newly emerging antifolate-resistant malaria parasites. Recently, in vitro metabolism of a new series of phenoxypropoxybiguanide analogs has examined the production of the active triazine metabolites by human liver microsomes. The purpose of this investigation was to elucidate the primary cytochrome P450 isoforms involved in the production of active metabolites in the current lead candidate. By using expressed human recombinant isoform preparations, specific chemical inhibitors, and isoform-specific inhibitory antibodies, the primary cytochrome P450 isoforms involved in the in vitro metabolic activation of JPC-2056 were elucidated. Unlike proguanil, which is metabolized primarily by CYP2C19, the results indicate that CYP3A4 plays a more important role in the metabolism of both PS-15 and JPC-2056. Whereas CYP2D6 appears to play a major role in the metabolism of PS-15 to WR99210, it appears less important in the conversion of JPC-2056 to JPC-2067. These results are encouraging, considering the prominence of CYP2C19 and CYP2D6 polymorphisms in certain populations at risk for contracting malaria, because the current clinical prodrug candidate from this series may be less dependent on these enzymes for metabolic activation.

Automated Pain Assessment using Electrodermal Activity Data and Machine Learning.

Objective pain assessment is required for appropriate pain management in the clinical setting. However, clinical gold standard pain assessment is based on subjective methods. Automated pain detection from physiological data may provide important objective information to better standardize pain assessment. Specifically, electrodermal activity (EDA) can identify features of stress and anxiety induced by varying pain levels. However, notable variability in EDA measurement exists and research to date has demonstrated sensitivity but lack of specificity in pain assessment. In this paper, we use timescale decomposition (TSD) to extract salient features from EDA signals to identify an accurate and automated EDA pain detection algorithm to sensitively and specifically distinguish pain from no-pain conditions.

Automated Pain Detection in Facial Videos of Children using Human-Assisted Transfer Learning.

Accurately determining pain levels in children is difficult, even for trained professionals and parents. Facial activity provides sensitive and specific information about pain, and computer vision algorithms have been developed to automatically detect Facial Action Units (AUs) defined by the Facial Action Coding System (FACS). Our prior work utilized information from computer vision, i.e., automatically detected facial AUs, to develop classifiers to distinguish between pain and no-pain conditions. However, application of pain/no-pain classifiers based on automated AU codings across different environmental domains results in diminished performance. In contrast, classifiers based on manually coded AUs demonstrate reduced environmentally-based variability in performance. In this paper, we train a machine learning model to recognize pain using AUs coded by a computer vision system embedded in a software package called iMotions. We also study the relationship between iMotions (automatically) and human (manually) coded AUs. We find that AUs coded automatically are different from those coded by a human trained in the FACS system, and that the human coder is less sensitive to environmental changes. To improve classification performance in the current work, we applied transfer learning by training another machine learning model to map automated AU codings to a subspace of manual AU codings to enable more robust pain recognition performance when only automatically coded AUs are available for the test data. With this transfer learning method, we improved the Area Under the ROC Curve (AUC) on independent data from new participants in our target domain from 0.67 to 0.72.

Towards Automated Pain Detection in Children using Facial and Electrodermal Activity.

Accurately determining pain levels in children is difficult, even for trained professionals and parents. Facial activity and electro- dermal activity (EDA) provide rich information about pain, and both have been used in automated pain detection. In this paper, we discuss preliminary steps towards fusing models trained on video and EDA features respectively. We compare fusion models using original video features and those using transferred video features which are less sensitive to environmental changes. We demonstrate the benefit of the fusion and the transferred video features with a special test case involving domain adaptation and improved performance relative to using EDA and video features alone.

Discovery of LX2761, a Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitor Restricted to the Intestinal Lumen, for the Treatment of Diabetes.

The increasing number of people afflicted with diabetes throughout the world is a major health issue. Inhibitors of the sodium-dependent glucose cotransporters (SGLT) have appeared as viable therapeutics to control blood glucose levels in diabetic patents. Herein we report the discovery of LX2761, a locally acting SGLT1 inhibitor that is highly potent in vitro and delays intestinal glucose absorption in vivo to improve glycemic control.

Tetraoxane antimalarials and their reaction with Fe(II).

Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4' ') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg.kg-1.day-1, and 2/5 mice at 50 mg.kg-1.day-1, showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO* radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO* radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed.

In vitro metabolism of phenoxypropoxybiguanide analogues in human liver microsomes to potent antimalarial dihydrotriazines.

Phenoxypropoxybiguanides, such as 1 (PS-15), are prodrugs analogous to the relationship of proguanil and its active metabolite cycloguanil. Unlike cycloguanil, however, 1a (WR99210), the active metabolite of 1, has retained in vitro potency against newly emerging antifolate-resistant malaria parasites. Unfortunately, manufacturing processes and gastrointestinal intolerance have prevented the clinical development of 1. In vitro antimalarial activity and in vitro metabolism studies have been performed on newly synthesized phenoxypropoxybiguanide analogues. All of the active dihydrotriazine metabolites exhibited potent antimalarial activity with in vitro IC(50) values less than 0.04 ng/mL. In vitro metabolism studies in human liver microsomes identified the production of not only the active dihydrotriazine metabolite, but also a desalkylation on the carbonyl chain, and multiple hydroxylated metabolites. The V(max) for production of the active metabolites ranged from 10.8 to 27.7 pmol/min/mg protein with the K(m) ranging from 44.8 to 221 microM. The results of these studies will be used to guide the selection of a lead candidate.

The role of in vitro ADME assays in antimalarial drug discovery and development.

The high level of attrition of drugs in clinical development has led pharmaceutical companies to increase the efficiency of their lead identification and development through techniques such as combinatorial chemistry and high-throughput (HTP) screening. Since the major reasons for clinical drug candidate failure other than efficacy are pharmacokinetics and toxicity, attention has been focused on assessing properties such as metabolic stability, drug-drug interactions (DDI), and absorption earlier in the drug discovery process. Animal studies are simply too labor-intensive and expensive to use for evaluating every hit, so it has been necessary to develop and implement higher throughput in vitro ADME screens to manage the large number of compounds of interest. The antimalarial drug development program at the Walter Reed Army Institute of Research, Division of Experimental Therapeutics (WRAIR/ET) has adopted this paradigm in its search for a long-term prophylactic for the prevention of malaria. The overarching goal of this program is to develop new, long half-life, orally bioavailable compounds with potent intrinsic activity against liver- and blood-stage parasites. From the WRAIR HTP antimalarial screen, numerous compounds are regularly identified with potent activity. These hits are now immediately evaluated using a panel of in vitro ADME screens to identify and predict compounds that will meet our specific treatment criteria. In this review, the WRAIR ADME screening program for antimalarial drugs is described as well as how we have implemented it to predict the ADME properties of small molecule for the identification of promising drug candidates.

Indicadores para evaluar la correspondencia entre pertinencia y calidad en los egresados de Ciencias Médicas / Indicators to assess the correspondence between relevance and quality in graduates of Medical Sciences

Introducción:El reto que la sociedad actual propone a las universidades consiste en formar profesionales capaces de afrontar demandas laborales, desarrollar habilidades que les permita solucionar eficazmente las necesidades sociales, combinando conocimiento y habilidades intelectuales, manuales, sociales, actitudes para afrontar un problema profesional. Objetivo: Identificar los indicadores que permitan evaluar la correspondencia entre pertinencia del egresado de las Ciencias Médicas y la calidad de los servicios prestados en las instituciones de Atención Secundaria de Salud, provincia Mayabeque.Métodos: Se realizó un estudio descriptivo, transversal de abril 2018 a abril 2019 en las entidades de Atención Secundaria de Salud. El universo estuvo constituido por 250 graduados de las carreras de Ciencias Médicas, 100 estudiantes de Medicina, 50 de Estomatología y 100 de Indicadores para evaluar la correspondencia entre pertinencia y calidad en los egresados Tecnología de la Salud vinculados a las instituciones objeto de estudio y 100 pacientes que acudieron solicitando atención en el periodo estudiado. Resultados: Se identificaron 12 Indicadores para evaluar la pertinencia del egresado de las carreras de Ciencias Médicas, 26 Indicadores para caracterizar la calidad de los servicios brindados en las instituciones de Atención Secundaria de Salud y la correspondencia entre los indicadores de pertinencia y calidad Conclusiones: Existe correspondencia entre pertinencia del egresado de las carreras de Ciencias Médicas y la calidad de los servicios brindados en las instituciones de Atención Secundaria de Salud de la provincia Mayabeque. La correspondencia entre pertinencia y calidad será más eficiente en la medida en que se logre que los profesionales apliquen conocimientos y habilidades para solucionar.(AU)

Introduction:The challenge that today's society proposes to universities is to train professionals capable of facing job demands, developing skills that allow them to effectively solve social needs, combining knowledge and intellectual, manual, social skills, attitudes to face a professional problem. Objective: To identify the indicators that allow evaluating the correspondence between the relevance of the graduate of Medical Sciences and the quality of the services provided in the Secondary Health Care institutions, Mayabeque province. Methods: A descriptive, cross-sectional study was performed from April 2018 to April 2019 in the entities of Secondary Health Care. The universe was made up of 250 graduates from Medical Sciences careers, 100 Medicine, 50 Stomatology and 100 Health Technology students linked to the institutions under study and 100 patients who came seeking care in the period studied.Results:Twelve Indicators were identified to assess the relevance of the graduate of Medical Sciences careers, 26 indicators to characterize the quality of the services provided in the Secondary Health Care institutions and the correspondence between the indicators of relevance and quality. Conclusions: There is a correspondence between the relevance of the graduate of Medical Sciences careers and the quality of the services provided in the Secondary Health Care institutions of Mayabeque province. The correspondence between relevance and quality will be more efficient to the extent that professionals apply knowledge and skills to solve the population's health needs.(AU)

Consumo de antibióticos en dos servicios hospitalarios / Antibiotic consumption in two hospital services

Introducción: El uso excesivo e inadecuado de los antibióticos ha contribuido al incremento de la resistencia antimicrobiana y al aumento en los costos hospitalarios, lo que atenta contra la calidadasistencial.Objetivo: Determinar el consumo, el costo global y total de antibióticos en dos servicios hospitalarios.Métodos: Se realizó un estudio exploratorio, observacional, transversal, en el Hospital Clínico Quirúrgico Aleida Fernández Chardiet del municipio de Güines, provincia Mayabeque, en el períodocomprendido de enero a abril de 2019. La información primaria se obtuvo del reporte de consumo de antibióticos y se trabajó con el universo de antibióticos controlados registrados0que se prescribieron en los servicios de Medicina Interna y Cirugía. Las variablesse expresaron en frecuencias absolutas y relativas. Los resultados se mostraron en tablas y gráficos.Resultados: Los antibióticos más utilizados fueron: en un 25.6 % el Cefatoxime, 15.1 por ciento la Cefuroxima y en Facultad de Ciencias Médicas de Mayabeque 473 Consumo de antibióticos en dos servicios hospitalarios un 11.2 por ciento la Ceftriaxona. El mayor gasto por concepto de antibióticos controlados consumidos en esas salas correspondió en un 28.21 por ciento al mes de marzo, seguido por 27.57 por ciento en el mes de enero y un 24.41 % en el mes de febrero.Conclusiones: Las cefalosporinas constituyen el grupo farmacológico más empleado, el costo global de antibióticos consumidos en ambos servicios corresponden a las prescripciones de Ciprofloxacina y Ceftriaxona y el costo total de antibióticos incide en los meses de enero y marzo.(AU)

Introduction: The excessive and inadequate use of antibiotics has contributed to the increasing of the antimicrobial resistance and the hospital costs, which affects the assistance quality.Objective: To determine the consumption, the global cost and the total of antibiotics in two hospital services.Methods: An exploratory, observational, cross-sectional study was performed at Aleida Fernández Chardiet teaching Clinical Surgical hospital from Güines municipality, Mayabeque province,from January to April, 2019. The primary information was obtained from the report of antibiotics consumption and the research was based on the controlled universe of registered antibiotics that were prescribed in the Internal Medicine and Surgery Services The variableswere expressed in absolute and relative frequencies. The results were shown in tables and graphs.Results: The most used antibiotics were: in a 25.6 per cent Cefatoxime, 15.1 % Cefuroxime and in a 11.2 per cent laCeftriaxone. The highest expense for consumed controlled antibiotics in those wards corresponded in a 28.21 % to March, followed by 27.57 per cent in January and a 24.41 per cent in February.Conclusions: Cephalosporin constitute the most used pharmacological group, the global cost of consumed antibiotics in both services corresponded to the prescriptions of Ciprofloxacin and Ceftriaxoneand the total cost of antibiotics prevails in January and March.(AU)

Automated Assessment of Children's Postoperative Pain Using Computer Vision.

BACKGROUND: Current pain assessment methods in youth are suboptimal and vulnerable to bias and underrecognition of clinical pain. Facial expressions are a sensitive, specific biomarker of the presence and severity of pain, and computer vision (CV) and machine-learning (ML) techniques enable reliable, valid measurement of pain-related facial expressions from video. We developed and evaluated a CVML approach to measure pain-related facial expressions for automated pain assessment in youth. METHODS: A CVML-based model for assessment of pediatric postoperative pain was developed from videos of 50 neurotypical youth 5 to 18 years old in both endogenous/ongoing and exogenous/transient pain conditions after laparoscopic appendectomy. Model accuracy was assessed for self-reported pain ratings in children and time since surgery, and compared with by-proxy parent and nurse estimates of observed pain in youth. RESULTS: Model detection of pain versus no-pain demonstrated good-to-excellent accuracy (Area under the receiver operating characteristic curve 0.84-0.94) in both ongoing and transient pain conditions. Model detection of pain severity demonstrated moderate-to-strong correlations (r = 0.65-0.86 within; r = 0.47-0.61 across subjects) for both pain conditions. The model performed equivalently to nurses but not as well as parents in detecting pain versus no-pain conditions, but performed equivalently to parents in estimating pain severity. Nurses were more likely than the model to underestimate youth self-reported pain ratings. Demographic factors did not affect model performance. CONCLUSIONS: CVML pain assessment models derived from automatic facial expression measurements demonstrated good-to-excellent accuracy in binary pain classifications, strong correlations with patient self-reported pain ratings, and parent-equivalent estimation of children's pain levels over typical pain trajectories in youth after appendectomy.

LP-925219 maximizes urinary glucose excretion in mice by inhibiting both renal SGLT1 and SGLT2.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents that improve glycemic control by inhibiting SGLT2-mediated renal glucose reabsorption. Currently available agents increase urinary glucose excretion (UGE) to <50% of maximal values because they do not inhibit SGLT1, which reabsorbs >50% of filtered glucose when SGLT2 is completely inhibited. This led us to test whether LP-925219, a small molecule dual SGLT1/SGLT2 inhibitor, increases UGE to maximal values in wild-type (WT) mice. We first tested LP-925219 inhibition of glucose transport by HEK293 cells expressing SGLT1 or SGLT2, and then characterized LP-925219 pharmacokinetics. We found that LP-925219 was a potent inhibitor of mouse SGLT1 (IC50 = 22.6 nmol/L) and SGLT2 (IC50 = 0.5 nmol/L), and that a 10 mg/kg oral dose was bioavailable (87%) with a long half-life (7 h). We next delivered LP-925219 by oral gavage to WT, SGLT1 knockout (KO), SGLT2 KO, and SGLT1/SGLT2 double KO (DKO) mice and measured their 24-h UGE. We found that, in vehicle-treated mice, DKO UGE was maximal and SGLT2 KO, SGLT1 KO, and WT UGEs were 30%, 2%, and 0.2% of maximal, respectively; we also found that LP-925219 dosed at 60 mg/kg twice daily increased UGE of SGLT1 KO, SGLT2 KO, and WT mice to DKO UGE levels. These findings show that orally available dual SGLT1/SGLT2 inhibitors can maximize 24-h UGE in mammals, and suggest that such agents merit further evaluation for their potential, in diabetic patients, to achieve better glycemic control than is achieved using selective SGLT2 inhibitors.

Resultados alcanzados en los subsistemas de Ciencia e Innovación Tecnológica provincia Mayabeque año 2018 / Obtained results in the subsystems of Science and Technological Innovation in Mayabeque, 2018

Introducción: la ciencia constituye un complejo fenómeno social que tiene como propósito la producción, difusión y aplicación de conocimientos. En la universidad cubana, el proceso de ciencia e innovación tecnológica promueve la introducción y generalización de resultados científicos que garanticen impactos sostenibles.Objetivo: describir el comportamiento de algunos de los subsistemas de Ciencia e Innovación Tecnológica en la provincia Mayabeque como resultado de la implementación de la Carpeta Metodológica de Ciencia y Técnica.Métodos: se realizó un estudio descriptivo, transversal en el departamento de Ciencia e Innovación Tecnológica de la Facultad de Ciencias Médicas de Mayabeque, de enero a diciembre del 2018. El universo estuvo constituido por los subsistemas que conduce la dirección de Ciencia y Técnica. Para la selección de la muestra se utilizó un método no probabilístico, intencional, quedando conformada por cuatro subsistemas: proyectos, resultados científicos técnicos, producción científica, y categoría científica.Resultados: predominaron los proyectos de Tesis de Terminación de Residencia (91.06 %), de los resultados científicos el 33.33 % correspondieron a los problemas de grupos especiales, se incrementaron las publicaciones en un 50,6 % con respecto al año 2017, se aprobaron nueve expedientes de investigadores, se obtuvieron dos premios Joven Investigador, un premio del Ministerio de Ciencia Tecnología y Medio Ambiente y tres Premios Anuales de Salud.Conclusiones: la implementación de la Carpeta Metodológica de Ciencia e Innovación Tecnológica en Sedes Universitarias y entidades de Atención Primaria y Secundaria de Salud logra resultados relevantes en alguno de los subsistemas de Ciencia y Técnica en la provincia Mayabeque.(AU)

Introduction: science constitutes a complex social phenomenon with the purpose of production, diffusion and application of knowledge. In the Cuban Universities, the process of science and technological innovation promotes the promotion and generalization of scientific results that garantee sustainable impacts.Objective: to describe the behavior of some subsystems of science and technological innovation in Mayabeque as a result of the implementation of Science and Technics Methodological dossier.Methods: a descriptive, transversal study was carried out in the department of science and technological innovation of Mayabeque Faculty of Medical Sciences, from January to December, 2018. The Universe was composed by the subsystems under the Science and Technics direction. For the selection of the sample a non-probabilistic, intentional method was used, and it was formed by four subsystems: projects, scientific and technical results, scientific production, and scientific category.Results: projects related to residence final theses prevailed (91.06 %), related to the Scientific results the 33.33 % corresponded problems of special groups, publications were increased in a 96.5 % taking into account 2017, nine investigators records were approved , two “Young Investigator” prizes were obtained, A prize of the Ministry of Science , Technology and Environment and three Annual Health Prize.Conclusions: the implementation of the Science and Technological Innovation dossier in University centers, Primary and Secondary Health Care Institutions obtained relevant results in one of the subsystems of Science and Technics in Mayabeque province.(AU)