Evaluation of clinical practice guideline-derived clinical decision support systems using a novel quality model.

Over the last decade, clinical practice guidelines (CPGs) have become an important asset for daily life in healthcare organizations. Efficient management and digitization of CPGs help achieve organizational objectives and improve patient care and healthcare quality by reducing variability. However, digitizing CPGs is a difficult, complex task because they are usually expressed as text, and this often leads to the development of partial software solutions. At present, different research proposals and CPG-derived CDSS (clinical decision support system) do exist for managing CPG digitalization lifecycles (from modeling to deployment and execution), but they do not all provide full lifecycle support, making it more difficult to choose solutions or proposals that fully meet the needs of a healthcare organization. This paper proposes a method based on quality models to uniformly compare and evaluate technological tools, providing a rigorous method that uses qualitative and quantitative analysis of technological aspects. In addition, this paper also presents how this method has been instantiated to evaluate and compare CPG-derived CDSS by highlighting each phase of the CPG digitization lifecycle. Finally, discussion and analysis of currently available tools are presented, identifying gaps and limitations.

Retrospective Evaluation of Cytogenetic Effects Induced by Internal Radioiodine Exposure: A 27-Year Follow-Up Study.

Radioiodine (131I) is widely used in the treatment of hyperthyroidism and as an effective ablative therapy for differentiated thyroid cancer. Radioiodine (131I) constitutes 90% of the currently used therapies in the field of nuclear medicine. Here, we report the cytogenetic findings of a long-term follow-up study of 27 years on a male patient who received two rounds of radioiodine treatment within a span of 26 months between 1992 and 1994 for his papillary thyroid cancer. A comprehensive cytogenetic follow-up study utilizing cytokinesis blocked micronucleus assay, dicentric chromosome assay, genome wide translocations and inversions was initiated on this patient since the first administration of radioiodine in 1992. Frequencies of micronuclei (0.006/cell) and dicentric chromosomes (0.008/cell) detected in the current study were grossly similar to that reported earlier in 2019. The mFISH analysis detected chromosome aberrations in 8.6% of the cells in the form of both unbalanced and balanced translocations. Additionally, a clonal translocation involving chromosomes 14p; 15q was observed in 2 of the 500 cells analyzed. Out of the 500 cells examined, one cell showed a complex translocation (involving chromosomes 9, 10, and 16) besides 5 other chromosome rearrangements. Collectively, our study indicates that the past radioiodine exposure results in long-lasting chromosome damage and that the persistence of translocations can be useful for both retrospective biodosimetry and for monitoring chromosome instability in the lymphocytes of radioiodine exposed individuals.

Evaluation of Low-dose Radiation-induced DNA Damage and Repair in 3D Printed Human Cellular Constructs.

ABSTRACT: DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) are considered to be the most critical lesion that when unrepaired or misrepaired leads to genomic instability or cell death depending on the radiation exposure dose. The potential health risks associated with exposures of low-dose radiation are of concern since they are being increasingly used in diverse medical and non-medical applications. Here, we have used a novel human tissue-like 3-dimensional bioprint to evaluate low-dose radiation-induced DNA damage response. For the generation of 3-dimensional tissue-like constructs, human hTERT immortalized foreskin fibroblast BJ1 cells were extrusion printed and further enzymatically gelled in a gellan microgel-based support bath. Low-dose radiation-induced DSBs and repair were analyzed in the tissue-like bioprints by indirect immunofluorescence using a well-known DSB surrogate marker, 53BP1, at different post-irradiation times (0.5 h, 6 h, and 24 h) after treatment with various doses of γ rays (50 mGy, 100 mGy, and 200 mGy). The 53BP1 foci showed a dose dependent induction in the tissue bioprints after 30 min of radiation exposure and subsequently declined at 6 h and 24 h in a dose-dependent manner. The residual 53BP1 foci number observed at 24 h post-irradiation time for the γ-ray doses of 50 mGy, 100 mGy, and 200 mGy was not statistically different from mock treated bioprints illustrative of an efficient DNA repair response at these low-dose exposures. Similar results were obtained for yet another DSB surrogate marker, γ-H2AX (phosphorylated form of histone H2A variant) in the human tissue-like constructs. Although we have primarily used foreskin fibroblasts, our bioprinting approach-mimicking a human tissue-like microenvironment-can be extended to different organ-specific cell types for evaluating the radio-response at low-dose and dose-rates of IR.

Tele-entomology and tele-parasitology: A citizen science-based approach for surveillance and control of Chagas disease in Venezuela.

Chagas Disease (CD), a chronic infection caused by the Trypanosoma cruzi parasite, is a Neglected Tropical Disease endemic to Latin America. With a re-emergence in Venezuela during the past two decades, the spread of CD has proved susceptible to, and inhibitable by a digital, real-time surveillance system effectuated by Citizen Scientists in communities throughout the country. The #TraeTuChipo (#BringYourKissingBug) campaign implemented in January 2020, has served as such a strategy counting on community engagement to define the current ecological distribution of CD vectors despite the absence of a functional national surveillance program. This pilot campaign collected data through online surveys, social media platforms, and/or telephone text messages. A total of 79 triatomine bugs were reported from eighteen Venezuelan states; 67 bugs were identified as Panstrongylus geniculatus, 1 as Rhodnius pictipes, 1 as Triatoma dimidiata, and 10 as Triatoma maculata. We analyzed 8 triatomine feces samples spotted from 4 Panstrongylus geniculatus which were confirmed positive by qPCR for T. cruzi . Further molecular characterization of discrete typing units (DTUs), revealed that all samples contained TcI, the most highly diverse and broadly distributed strain of T. cruzi. Moreover, analysis of the mitochondrial 12S gene revealed Myotis keaysi, Homo sapiens, and Gallus gallus as the main triatomine feeding sources. This study highlights a novel Citizen Science approach which may help improve the surveillance systems for CD in endemic countries.

Lean requirements traceability automation enabled by model-driven engineering.

BACKGROUND: The benefits of requirements traceability, such as improvements in software product and process quality, early testing, and software maintenance, are widely described in the literature. Requirements traceability is a critical, widely accepted practice. However, very often it is not applied for fear of the additional costs associated with manual efforts or the use of additional tools. METHODS: This article presents a "low-cost" mechanism for automating requirements traceability based on the model-driven paradigm and formalized by a metamodel for the creation and monitoring of traces and an integration process for traceability management. This approach can also be useful for information fusion in industry insofar that it facilitates data traceability. RESULTS: This article extends an existing model-driven development methodology to incorporate traceability as part of its development tool. The tool has been used successfully by several companies in real software development projects, helping developers to manage ongoing changes in functional requirements. One of those projects is cited as an example in the paper. The authors' current work leads them to conclude that a model-driven engineering approach, traditionally used only for the automatic generation of code in a software development process, can also be used to successfully automate and integrate traceability management without additional costs. The systematic evaluation of traceability management in industrial projects constitutes a promising area for future work.

A comparative validation of biodosimetry and physical dosimetry techniques for possible triage applications in emergency dosimetry.

Large-scale radiological accidents or nuclear terrorist incidents involving radiological or nuclear materials can potentially expose thousands, or hundreds of thousands, of people to unknown radiation doses, requiring prompt dose reconstruction for appropriate triage. Two types of dosimetry methods namely, biodosimetry and physical dosimetry are currently utilized for estimating absorbed radiation dose in humans. Both methods have been tested separately in several inter-laboratory comparison exercises, but a direct comparison of physical dosimetry with biological dosimetry has not been performed to evaluate their dose prediction accuracies. The current work describes the results of the direct comparison of absorbed doses estimated by physical (smartphone components) and biodosimetry (dicentric chromosome assay (DCA) performed in human peripheral blood lymphocytes) methods. For comparison, human peripheral blood samples (biodosimetry) and different components of smartphones, namely surface mount resistors (SMRs), inductors and protective glasses (physical dosimetry) were exposed to different doses of photons (0-4.4 Gy; values refer to dose to blood after correction) and the absorbed radiation doses were reconstructed by biodosimetry (DCA) and physical dosimetry (optically stimulated luminescence (OSL)) methods. Additionally, LiF:Mg,Ti (TLD-100) chips and Al2O3:C (Luxel) films were used as reference TL and OSL dosimeters, respectively. The best coincidence between biodosimetry and physical dosimetry was observed for samples of blood and SMRs exposed toγ-rays. Significant differences were observed in the reconstructed doses by the two dosimetry methods for samples exposed to x-ray photons with energy below 100 keV. The discrepancy is probably due to the energy dependence of mass energy-absorption coefficients of the samples extracted from the phones. Our results of comparative validation of the radiation doses reconstructed by luminescence dosimetry from smartphone components with biodosimetry using DCA from human blood suggest the potential use of smartphone components as an effective emergency triage tool for high photon energies.

Cytogenetic follow-up studies on humans with internal and external exposure to ionizing radiation.

Cells exposed to ionizing radiation have a wide spectrum of DNA lesions that include DNA single-strand breaks, DNA double-strand breaks (DSBs), oxidative base damage and DNA-protein crosslinks. Among them, DSB is the most critical lesion, which when mis-repaired leads to unstable and stable chromosome aberrations. Currently, chromosome aberration analysis is the preferred method for biological monitoring of radiation-exposed humans. Stable chromosome aberrations, such as inversions and balanced translocations, persist in the peripheral blood lymphocytes of radiation-exposed humans for several years and, therefore, are potentially useful tools to prognosticate the health risks of radiation exposure, particularly in the hematopoietic system. In this review, we summarize the cytogenetic follow-up studies performed by REAC/TS (Radiation Emergency Assistance Center/Training site, Oak Ridge, USA) on humans exposed to internal and external radiation. In the light of our observations as well as the data existing in the literature, this review attempts to highlight the importance of follow-up studies for predicting the extent of genomic instability and its impact on delayed health risks in radiation-exposed victims.

Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage.

Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.

Detection of Simple, Complex, and Clonal Chromosome Translocations Induced by Internal Radioiodine Exposure: A Cytogenetic Follow-Up Case Study after 25 Years.

Here, we report the findings of a 25-year cytogenetic follow-up study on a male patient who received 2 rounds of radioiodine treatment within a span of 26 months (1.78 GBq in 1992 and 14.5 GBq in 1994). The patient was 34 years old with a body mass index of 25 at the time of the first radioiodine treatment. Multicolor FISH and multicolor banding (mBAND) techniques performed on the patient detected inter- and intrachromosomal exchanges. Although the frequency of chromosome translocations remained essentially the same as reported in our earlier study (0.09/cell), the percentage of reciprocal (balanced) translocations increased from 54.38 to 80.30% in the current study. In addition to simple chromosome translocations, complex exchanges (0.29%) involving more than 2 chromosomes were detected for the first time in this patient. Strikingly, a clonal translocation involving chromosomes 14 and 15, t(14p;15q), was found in 7 of the 677 cells examined (1.03%). The presence of complex and clonal translocations indicates the onset of chromosomal instability induced by internal radioiodine exposure. mBAND analysis using probes specific for chromosomes 1, 2, 4, 5, and 10 revealed 5 inversions in a total of 717 cells (0.69%), and this inversion frequency is several-fold higher than the baseline frequency reported in healthy individuals using the classical G-banding technique. Collectively, our study suggests that stable chromosome aberrations such as translocations and inversions can be useful not only for retrospective biodosimetry but also for long-term monitoring of chromosomal instability caused by past radioiodine exposure.

Optimization and validation of automated dicentric chromosome analysis for radiological/nuclear triage applications.

Dicentric Chromosome Assay (DCA) is the most preferred cytogenetic technique for absorbed radiation dose assessment in exposed humans. However, DCA is somewhat impractical for triage application owing to its labor intensive and time consuming nature. Although lymphocyte culture for 48 h in vitro is inevitable for DCA, manual scoring of dicentric chromosomes (DCs) requires an additional time of 24-48 h, making the overall turnaround time of 72-96 h for dose estimation. To accelerate the speed of DC analysis for dose estimation, an automated tool was optimized and validated for triage mode of scoring. Several image training files were created to improve the specificity of automated DC analysis algorithm. Accuracy and efficiency of the automated (unsupervised) DC scoring was compared with the semi-automated scoring that involved human verification and correction of DCs (elimination of false positives and inclusion of true positives). DC scoring was performed by both automated and semi-automated modes for different doses of X-rays and γ-rays (0 Gy-5 Gy). Biodoses estimated from the frequencies of DCs detected by both automated (unsupervised) and semi-automated (supervised) scoring modes were grossly similar to the actual delivered doses in the range of 0.5 to 3 Gy of low LET radiation. We suggest that the automated DC tool can be effectively used for large scale radiological/nuclear incidents where a rapid segregation is essential for prioritizing moderately or severely exposed humans to receive appropriate medical countermeasures.

2D Triangulation of Signals Source by Pole-Polar Geometric Models.

The 2D point location problem has applications in several areas, such as geographic information systems, navigation systems, motion planning, mapping, military strategy, location and tracking moves. We aim to present a new approach that expands upon current techniques and methods to locate the 2D position of a signal source sent by an emitter device. This new approach is based only on the geometric relationship between an emitter device and a system composed of m≥2 signal receiving devices. Current approaches applied to locate an emitter can be deterministic, statistical or machine-learning methods. We propose to perform this triangulation by geometric models that exploit elements of pole-polar geometry. For this purpose, we are presenting five geometric models to solve the point location problem: (1) based on centroid of points of pole-polar geometry, PPC; (2) based on convex hull region among pole-points, CHC; (3) based on centroid of points obtained by polar-lines intersections, PLI; (4) based on centroid of points obtained by tangent lines intersections, TLI; (5) based on centroid of points obtained by tangent lines intersections with minimal angles, MAI. The first one has computational cost On and whereas has the computational cost Onlognwhere n is the number of points of interest.

Development of electronic training and telescoring tools to increase the surge capacity of dicentric chromosome scorers for radiological/nuclear mass casualty incidents.

Dicentric chromosome assay (DCA) is most frequently used for estimating the absorbed radiation dose in the peripheral blood lymphocytes of humans after occupational or incidental radiation exposure. DCA is considered to be the "gold standard" for estimating the absorbed radiation dose because the dicentric chromosome formation is fairly specific to ionizing radiation exposure and its baseline frequency is extremely low in non-exposed humans. However, performance of DCA for biodosimetry is labor intensive and time-consuming making its application impractical for radiological/nuclear mass casualty incidents. Realizing the critical need for rapid dose estimation particularly after radiological/nuclear disaster events, several laboratories have initiated efforts to automate some of the procedural steps involved in DCA. Although metaphase image capture and dicentric chromosome analysis have been automated using commercially available platforms, lack or an insufficient number of these platforms may pose a serious bottleneck when hundreds and thousands of samples need to be analyzed for rapid dose estimation. To circumvent this problem, a web-based approach for telescoring was initiated by our laboratory, which enabled the cytogeneticists around the globe to analyze and score digital images. To further increase the surge capacity of dicentric scorers, we recently initiated a dicentric training and scoring exercise involving a total of 50 volunteers at all academic levels without any prerequisite for experience in radiation cytogenetics. Out of the 50 volunteers enrolled thus far, only one outlier was found who overestimated the absorbed radiation dose. Our approach of training the civilians in dicentric chromosome analysis holds great promise for increasing the surge capacity of dicentric chromosome scorers for a rapid biodosimetry in the case of mass casualty scenarios.

Extension of lymphocyte viability for radiation biodosimetry: Potential implications for radiological/nuclear mass casualty incidents.

Dicentric chromosome assay (DCA) is routinely used for estimating the absorbed radiation dose in exposed humans. Optimal lymphocyte viability is crucial for reliable dose estimation and most cytogenetic laboratories prefer the receipt of blood samples within 24 to 36 hours after collection. Delays in the shipment/receipt of samples can occur sometimes under certain unforeseen circumstances: (1) Adverse weather conditions, (2) distant location of blood collection sites, and (3) shipping and handling of a large number of samples after radiological/nuclear mass casualty incident(s). To circumvent some of these limitations, we evaluated the suitability of ex vivo irradiated blood samples stored in the presence of phytohemagglutinin (PHA) for 7 days at ambient temperature (22-24°C) for radiation biodosimetry. Blood samples stored in the presence of PHA for up to 7 days showed a higher mitotic index than blood samples stored without PHA. To verify the use of stored blood samples for DCA, frequencies of X-rays induced dicentric chromosomes were analyzed in the blood samples that were cultured either 24 hours after exposure or 7 days later after storage. Our results indicate that storage of ex vivo irradiated blood samples in the presence of PHA at ambient temperature was found optimal for DCA and that the radiation doses estimated by dicentric chromosome frequencies were grossly similar between the fresh and stored blood samples. Our study suggests that reliable and accurate biodosimetry results can be obtained for triage using blood samples stored for up to a week at ambient temperature in the presence of PHA.

DEVELOPMENT OF A MINIATURIZED VERSION OF DICENTRIC CHROMOSOME ASSAY TOOL FOR RADIOLOGICAL TRIAGE.

Use of ionizing radiation (IR) in various industrial, medical and other applications can potentially increase the risk of medical, occupational or accidental human exposure. Additionally, in the event of a radiological or nuclear (R/N) incident, several tens of hundreds and thousands of people are likely to be exposed to IR. IR causes serious health effects including mortality from acute radiation syndrome and therefore it is imperative to determine the absorbed radiation dose, which will enable physicians in making an appropriate clinical 'life-saving' decision. The 'Dicentric Chromosome Assay (DCA)' is the gold standard for estimating the absorbed radiation dose but its performance is time consuming and laborious. Further, timely evaluation of dicentric chromosomes (DCs) for dose estimation in a large number of samples provides a bottleneck because of a limited number of trained personnel and a prolonged time for manual analysis. To circumvent some of these technical issues, we developed and optimized a miniaturized high throughput version of DCA (mini-DCA) in a 96-microtube matrix with bar-coded 1.4 ml tubes to enable the processing of a large number of samples. To increase the speed of DC analysis for radiation dose estimation, a semi-automated scoring was optimized using the Metafer DCScore algorithm. The accuracy of mini-DCA in dose estimation was verified and validated though comparison with conventional DCA performed in 15 ml conical tubes. The mini-DCA considerably reduced the sample processing time by a factor of 4 when compared to the conventional DCA. Further, the radiation doses estimated by mini-DCA using the triage mode of scoring (50 cells or 30 DCs) were similar to that of conventional DCA using 300-500 cells. The mini-DCA coupled with semi-automated DC scoring not only reduced the sample processing and analysis times by a factor of 4 but also enabled the processing of a large number of samples at once. Our mini-DCA method, once automated for high throughput robotic platforms, will be an effective radiological triage tool for mass casualty incidents.

Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow-up study using multicolor FISH.

Our previous studies demonstrated the cytogenetic effects in the peripheral blood lymphocytes of a 34-year-old male patient who received ablative radioactive 131iodine therapy (RIT) on two different occasions in 1992 and 1994. Assessment of RIT-induced chromosomal damage by the cytokinesis-blocked micronucleus assay (CBMN) showed the persistence of elevated micronucleus frequency in this patient for more than two decades since the first RIT. Subsequent cytogenetic analysis performed in 2012 revealed both stable and unstable aberrations, whose frequencies were higher than the baseline reported in the literature. Here, we report the findings of our recent cytogenetic analysis peformed in 2015 on this patient using the multicolor fluorescence in situ hybridization (mFISH) technique. Our results showed that both reciprocal and non-reciprocal translocations persisted at higher frequencies in the patient than those reported in 2012. Persistence of structural aberrations for more than two decades indicate that these aberrations might have originated from long-lived T-lymphocytes or hematopoietic stem cells. Our study suggests that the long-term persistence of chromosome translocations in circulating lymphocytes can be useful for monitoring the extent of RIT-induced chromosomal instability several years after exposure and for estimating the cumulative absorbed dose after multiple RITs for retrospective biodosimetry purposes. This is perhaps the first and longest follow-up study documenting the persistence of cytogenetic damage for 21 years after internal radiation exposure.

Magnetic solid lipid nanoparticles in hyperthermia against colon cancer.

A reproducible double emulsion/solvent evaporation procedure is developed to formulate magnetic solid lipid nanoparticles (average size≈180 nm) made of iron oxide cores embedded within a glyceryl trimyristate solid matrix. The physicochemical characterization of the nanocomposites ascertained the efficacy of the preparation conditions in their production, i.e. surface properties (electrokinetic and thermodynamic data) were almost indistinguishable from those of the solid lipid nanomatrix, while electron microscopy characterizations and X-ray diffraction patterns confirmed the satisfactory coverage of the magnetite nuclei. Hemocompatibility of the particles was established in vitro. Hysteresis cycle determinations defined the appropriate magnetic responsiveness of the nanocomposites, and their heating characteristics were investigated in a high frequency alternating gradient of magnetic field: a constant maximum temperature of 46 °C was obtained within 40 min. Finally, in vitro tests performed on human HT29 colon adenocarcinoma cells demonstrated a promising decrease in cell viability after treatment with the nanocomposites and exposure to that alternating electromagnetic field. To the best of our knowledge, this is the first time that such type of nanoformulation with very promising hyperthermia characteristics has been developed for therapeutic aims.

Caracterización de la familia del adulto mayor / Characterization of the elderly family

El envejecimiento en la familia constituye un problema mundial y nacional, teniendo en cuenta esa premisa se realizó un estudio de tipo descriptivo, con el uso de técnicas cuantitativas y cualitativas, para caracterizar las familias donde viven adultos mayores, pertenecientes al área de salud del policlínico docente Dr. Gustavo Aldereguía Lima. Se seleccionaron al azar diez familias del área incluida en el consultorio médico de la familia 94-01 que cumplieran con los criterios de inclusión, las que se caracterizaron a través de las variables socio-psicológicas: estructura, crisis, funcionamiento y percepción familiar; los datos se obtuvieron a partir de las técnicas de entrevista a la familia, la prueba de percepción de funcionamiento familiar (FF-SIL) y la prueba de percepción de las relaciones familiares. En las familias estudiadas predominó la existencia de una estructura pequeña; nuclear y unigeneracional; multigeneracional. Las funciones que mejor cumplieron las familias fueron la económica y la educativo-cultural; y las crisis normativas que predominaron fueron la jubilación, el envejecimiento y la enfermedad. El funcionamiento familiar que prevaleció fue el funcional; los indicadores más afectados fueron los roles, la permeabilidad, la comunicación y la adaptabilidad; en la percepción familiar predominaron las familias armónicas, seguidas de las poco armónicas. Los indicadores más afectados fueron el sistema de apoyo, la comunicación y el desempeño de roles. Se concluyó que las familias presentaron fundamentalmente una estructura pequeña y nuclear, son funcionales y son armónicas (AU

The aging process in the family is a world and national problem. Taking into account this premise, a descriptive study was carried out, using quantitative and qualitative techniques to characterize the families where elderly live. The population belonged to the health area of Dr. Gustavo Aldereguía Lima Teaching Polyclinic. The study included ten randomly selected families from the doctors office 94-01, which fulfilled the inclusion criteria. The families were characterized by means of the following socio-psychological variables: structure, crisis, family functionality and family perception. The data were obtained by means of the following techniques: the family interview, the family perception functionality test (FF-SIL) and the test for the perception of the family relations. In the studied families there was a prevalence of a small, nuclear, unigenerational and multigenerational structure. The functions best fulfilled by the families were the economic, educative and cultural ones. The prevailing normative crises were retirement, aging and disease.Family functionality prevailed. The most affected indicators were roles, permeability, communication and adaptability. Within family perception there was a prevalence of harmonious families followed by half-harmonious ones. The most affected indicators were system support, communication and role performance. The study concluded that the families were basically small and nuclear as well as functional and harmonious (AU)

High-content screening of natural products reveals novel nuclear export inhibitors.

Natural products are considered an extremely valuable source for the discovery of new drugs against diverse pathologies. As yet, we have only explored a fraction of the diversity of bioactive compounds, and opportunities for discovering new natural products leading to new drugs are huge. In the present study, U2nesRELOC, a previously established cell-based imaging assay, was employed to screen a collection of extracts of microbial origin for nuclear export inhibition activity. The fluorescent signal of untreated U2nesRELOC cells localizes predominantly to the cytoplasm. Upon treatment with the nuclear export inhibitor leptomycin B, the fluorescent-tagged reporter proteins appear as speckles in the nucleus. A proprietary collection of extracts from fungi, actinomycetes, and unicellular bacteria that covers an uncommonly broad chemical space was used to interrogate this nuclear export assay system. A two-step image-based analysis allowed us to identify 12 extracts with biological activities that are not associated with previously known active metabolites. The fractionation and structural elucidation of active compounds revealed several chemical structures with nuclear export inhibition activity. Here we show that substrates of the nuclear export receptor CRM1, such as Rev, FOXO3a and NF-κB, accumulate in the nucleus in the presence of the fungal metabolite MDN-0105 with an IC50 value of 3.4 µM. Many important processes in tumor formation and progression, as well as in many viral infections, critically depend on the nucleocytoplasmic trafficking of proteins and RNA molecules. Therefore, the disruption of nuclear export is emerging as a novel therapeutic approach with enormous clinical potential. Our work highlights the potential of applying high-throughput phenotypic imaging on natural product extracts to identify novel nuclear export inhibitors.

Propuesta de una estratégia para el fortalecimiento de la sección de farmacovigilancia del Departamento de Farmacia del Hospital Universitario de Caracas / Proposal for a strategy to strengthen the pharmacovigilance section of the Pharmacy Department of the University Hospital of Caracas

Las reacciones adversas a los medicamentos que ocasionan el ingreso hospitalario o la prolongación del tiempo de estancia hospitalaria tienen un gran impacto sanitario y económico; a pesar de esto, se conoce que existe una marcada subnotificación de estos eventos, en parte debido a la inexistencia de programas propios de las instituciones para realizar la notificación o a la falta de información de los profesionales de la salud acerca de la existencia de los mismos y la importancia de notificar. El Hospital Universitario de Caracas es una institución de conocido renombre y experticia en el área de la salud y tampoco escapa de esta problemática. Durante la investigación se pudo observar la subnotificación que se produce en el mismo y el inadecuado funcionamiento del programa de farmacovigilancia establecido en la institución, a través de la aplicación de encuestas y la realización de entrevistas al personal que labora en la misma. Finalmente se presenta una propuesta con los lineamientos básicos para la reactivación de dicho programa.

Adverse drug reactions causing hospital income or the prolongation of the hospital stay, have a great economic and sanitary impact; despite this, it is widely know that these events aren't notified or are sub notified to Health Authorities, in some cases this could be a consequence of the lack of pharmacovigilance programs in Hospitals or other institutions to do the notification, or could be also because an inadequate information of health care professionals about the existence of these programs or the importance of the notification. The "Hospital Universitario de Caracas" is a reputable institution related to health care that doesn't escape to these problems. Through the investigation we could notice the sub notification that occurs therein and the malfunction of the pharmacovigilance program that exists in this Institution, all this information was obtained through interviews and questionnaires conducted to the staff of the hospital. Finally a proposal with the basic guidelines to improve the program is presented.

Influencia del asma bronquial en el ausentismo escolar en niños de 5-12 años atendidos en la clínica de especialidades médicas de Bayamo / Influence of bronchial asthma in the absenteeism in children of 5-12 years attended in the Specialty clinic in Bayamo

Introducción: la importancia del asma en la infancia como problema sanitario no radica sólo en su mortalidad ni en la frecuencia de los ingresos hospitalarios. Un aspecto fundamental del asma reside en su carácter de enfermedad crónica que afecta a la calidad de vida y al desempeño social, educativo y laboral del niño y de su familia, incrementando el porcentaje de ausentismo escolar. Objetivo: caracterizar la influencia del asma bronquial en el ausentismo escolar en niños de 5 a 12 años atendidos en la clínica de especialidades Médicas de Bayamo, durante el periodo de enero a diciembre del 2011. Métodos: se realizó un estudio descriptivo de corte transversal en niños asmáticos atendidos en la clínica de especialidades médicas de Bayamo, durante el periodo de enero a diciembre del 2011, el universo estuvo constituido por 122 niños comprendidos en las edades de 5-12 años, de los cuales se seleccionó una muestra que estuvo conformada por los 51 niños asmáticos correspondientes las edades definidas para el estudio. Resultados: el grupo de edades de 5 a 8 años fue el más afectado con un 64,8 por ciento, predominando el sexo masculino, los principales factores de riesgos fueron la contaminación ambiental, los ácaros del polvo doméstico, y los cambios de temperatura, solo el 21,8 por ciento, de los niños que realizaron tratamiento intercrisis tuvieron ausentismo escolar mientras que los que no realizaron el tratamiento intercrisis presentaron un 100 por ciento de inasistencia escolar, los meses más afectados fueron diciembre y enero. Conclusiones: el asma bronquial constituye un serio problema de salud que repercute en el ámbito social por el ausentismo escolar que ocasiona, siendo de primordial importancia la atención de estos niños en los servicios de alergología al constatar un mayor perfil de seguridad en los tratamientos intercrisis indicados, con mejoramiento de la calidad de vida de estos pacientes y disminución del ausentismo por esta causa(AU)

Introduction: the importance of asthma in children like a sanitary problem not only lies in its mortality or in the frequency of the hospitalizations. A main sign of asthma lies in its character of chronic illness that affects the life quality and the social, educational and labour fulfilment of the children and their family, increasing the percentage of absenteeism. Objective: to characterize the influence of the bronchial asthma in the absenteeism in children of 5 to 12 years attended in the Medical specialty clinic in Bayamo, during the period of January to December of the 2011. Methods: it was performed a descriptive and transversal study in asthmatic children attended in the medical specialty clinic in Bayamo, during the period of January to December of the 2011, the universe was constituted by 122 children between the ages of 5-12 years, selecting a sample that was made by the 51 asthmatic children belonging to the ages for the study. Results: the group of ages of 5 to 8 years was the most affected with 64,8 percent, prevailing the male sex, the main risk factors were the environmental pollution, the acarids of the domestic dust, and the changes of temperature, only the 21,8 percent, of the children with inter-crisis treatment had absenteeism school whereas those that did not realize the inter-crisis treatment presented 100 percent of absenteeism, the most affected months were December and January. Conclusions: the bronchial asthma constitutes a serious health problem that has an impact in the social field for the absenteeism, being of paramount importance the attention of these children in the services of allergy when ascertaining a greater profile of security in the inter- crisis treatments indicated, with an improvement of the quality of life of these patients and the decrease of the absenteeism for this cause(EU)