127 results on '"Gavilanes, Antonio W."'
Search Results
2. Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador
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Guevara-Aguirre, Jaime, Bautista, Camila, Torres, Carlos, Peña, Gabriela, Guevara, Carolina, Palacios, Cristina, Guevara, Alexandra, and Gavilanes, Antonio W. D.
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- 2021
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3. Antenatal and Perioperative Mechanisms of Global Neurological Injury in Congenital Heart Disease
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Barkhuizen, Melinda, Abella, Raul, Vles, J. S. Hans, Zimmermann, Luc J. I., Gazzolo, Diego, and Gavilanes, Antonio W. D.
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- 2021
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4. 844: OPPORTUNITIES FOR IMPROVEMENT IN GRIEF AND BEREAVEMENT CARE IN PEDIATRIC INTENSIVE CARE UNITS
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Grunauer, Michelle, Mikesell, Caley, Bustamante, Gabriela, Zambrano, Kevin, Icaza-Freire, Andrea, Aronowitz, Danielle, Danilo Gavilanes, Antonio W., and Barrera, Rafael
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- 2022
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5. Exploring the role of information and communication technologies in allergic rhinitis in specialist centers: Patient perspectives on usefulness, value, and impact on healthcare.
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Cherrez‐Ojeda, Ivan, Bousquet, Jean, Sarfraz, Zouina, Sarfraz, Azza, Rodriguez Gonzales, Monica, Bedbrook, Anna, Rosario, Nelson, Zepeda‐Ortega, Benjamin, Guidos, Guillermo, Alcivar Molina, Ulbio, Felix, Miguel, Vanegas, Emanuel, Robles‐Velasco, Karla, Zimmermann, Luc J., and Gavilanes, Antonio W. D.
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PATIENTS' attitudes ,INFORMATION & communication technologies ,MEDICAL communication ,ALLERGIC rhinitis ,AUGMENTED reality ,PATIENT education ,MEDICAL care - Abstract
Introduction: Information and communication technologies (ICTs) improve patient‐centered care and are routinely used in Allergic Rhinitis (AR), but patients' preferences and attitudes are unexplored. This study examines AR‐related information preferences and ICT use by AR patients. Methods: A survey‐based cross‐sectional study was carried out in Ecuador from July to September 2019 in seven centers of reference for allergic disease. Participants were 18 years or older, diagnosed with AR and had access to ICT and the Internet. Descriptive and binomial logistic regressions were performed. A value of less than 0.05 was considered statistically significant. Results: 217 patients were included. 47% (n = 102) used ICTs to learn about AR, of which 38.2% (n = 83) found it useful. Most of participants (75%, n = 164) did not think that ICTs reduce their need to see a doctor. Individuals with poorer quality of life were more likely to utilize ICTs to contact their doctor (OR 1.27, 95% CI 1.04–1.55), and more likely to be interested in AR‐related content (OR 1.23, 95% CI 1.00–1.52). Patients with long‐term AR or other allergies were less likely to use ICTs (OR 0.92 and OR 0.40 respectively). Higher education and lower quality of life may increase AR apps adoption (OR 4.82, 95% CI 1.11–21.00). Academic preparation five‐fold increased ICT use for health provider communication (OR 5.29, 95% CI 1.18–23.72). Mild‐persistent AR enhanced the probabilities of using ICTs to share experiences and communicate with other patients (OR 12.59, 95% CI 1.32–120.35). Conclusions: Our study emphasizes the importance of tailoring digital resources to patient needs by considering factors such as quality of life, education, and specific subgroups within the AR patient population. Additionally, the findings suggest that while ICTs can play a valuable role in patient education and support, they should complement, rather than replace, traditional medical care for many AR patients. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Cancer in growth hormone excess and growth hormone deficit.
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Guevara-Aguirre, Jaime, Peña, Gabriela, Acosta, William, Pazmiño, Gabriel, Saavedra, Jannette, Soto, Lina, Lescano, Daniela, Guevara, Alexandra, and D Gavilanes, Antonio W
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SOMATOTROPIN ,TUMOR growth ,ACROMEGALY ,GAIN-of-function mutations ,COLON tumors ,BENIGN tumors - Abstract
The relationship between growth hormone (GH) excess and cancer is a controversial matter. Until 2016, most studies in patients with acromegaly found links with colon and thyroid neoplasms. However, recent studies found increased risks in gastric, breast, and urinary tract cancer also. Concordantly, clinical situations where GH and insulinlike growth facto-I deficits exist are indeed associated with diminished malignancy incidence. In line with these observations, gain-of-function mutations of various enzymes belonging to the GH and IGF-I signaling pathways have been associated with increased carcinogenesis; similarly, loss-of-function mutations of other enzymes that usually work as tumor repressors are also associated with augmented cancer risk. In a study performed in Ecuador, it was demonstrated that subjects in the Ecuadorian cohort with Laron syndrome (ELS), who have a mutant GH receptor and greatly diminished GH and IGF-I signaling, display diminished incidence of cancer. Along with absent action of GH and IGF-I, ELS individuals also have low serum insulin levels and decreased insulin resistance. Furthermore, hyperglycemia and hyperinsulinemia are indispensable for fast cell mitosis, including that of those cells present in the benign and malignant neoplasms. Notably, and despite their obesity, subjects with the ELS display normoglycemia and hypoinsulinemia, along with diminished incidence of malignancies. We believe that the dual low-IGF-I/low insulin serum levels are responsible for the cancer protection, especially considering that the insulin/INSR signaling is a central site for energy generation in the form of ATP and GDP, which are indispensable for all and every GH/IGF-I physiologic as well as pathologic events. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Mesenchymal stem/stromal cells—a key mediator for regeneration after perinatal morbidity?
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Mueller, Martin, Wolfs, Tim G. A., Schoeberlein, Andreina, Gavilanes, Antonio W. D., Surbek, Daniel, and Kramer, Boris W.
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- 2016
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8. Cancer in Ecuadorian subjects with Laron syndrome (ELS).
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Guevara-Aguirre, Jaime, Peña, Gabriela, Pazmiño, Gabriel, Acosta, William, Saavedra, Jannette, Lescano, Daniela, Guevara, Alexandra, and Gavilanes, Antonio W. D.
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HODGKIN'S disease ,NON-Hodgkin's lymphoma ,MULTIPLE myeloma ,SYNDROMES ,CARBOHYDRATE metabolism ,PITUITARY dwarfism ,THYROID cancer - Abstract
Meta-analyses from 2018-2022 have shown that obesity increases the risk of various cancers such as acute myeloid lymphoma, chronic myeloid lymphoma, diffuse beta cell lymphoma, Hodgkin's lymphoma, leukemia, multiple myeloma, non-Hodgkin's lymphoma, bladder, breast, cholangiocarcinoma, colorectal, ovarian, esophageal, kidney, liver, prostate, thyroid, and uterus. Contextually, obesity, and its comorbidities, is the largest, most lethal pandemics in the history of mankind; hence, identification of underlying mechanisms is needed to adequately address this global health threat. Herein, we present the metabolic and hormonal mechanisms linked to obesity that might etiologically contribute to neoplasia, including hyperinsulinemia and putative places in the insulin-signaling pathway. Excess insulin, acting as a growth factor, might contribute to tumorigenesis, while abundant ATP and GDP supply the additional energy needed for proliferation of rapidly dividing cells. Our observations in the Ecuadorian cohort of subjects with Laron syndrome (ELS) prove that obesity does not always associate with increased cancer risk. Indeed, despite excess body fat from birth to death, these individuals display a diminished incidence of cancer when compared to their age- and sex-matched relatives. Furthermore, in cell cultures exposed to potent oxidizing agents, addition of ELS serum induces less DNA damage as well as increased apoptosis. ELS individuals have absent growth hormone (GH) counter-regulatory effects in carbohydrate metabolism due to a defective GH receptor. The corresponding biochemical phenotype includes extremely low basal serum concentrations of insulin and insulin-like growth factor-I, lower basal glucose and triglyceride (TG) levels, and diminished glucose, TG, and insulin responses to orally administered glucose or to a mixed meal. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Cerebellar Cytokine Expression in a Rat Model for Fetal Asphyctic Preconditioning and Perinatal Asphyxia
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Vlassaks, Evi, Brudek, Tomasz, Pakkenberg, Bente, and Gavilanes, Antonio W. D.
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- 2014
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10. Tidal volume optimization and heart rate response during stabilization of very preterm infants.
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Cavigioli, Francesco, Bresesti, Ilia, Di Peri, Antonio, Cerritelli, Francesco, Gazzolo, Diego, Gavilanes, Antonio W. D., Kramer, Boris, te Pas, Arjan, and Lista, Gianluca
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- 2023
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11. Decreasing incidence rates of osteoporotic hip fractures in Ecuador during the COVID-19 pandemic.
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Lopez Gavilanez, Enrique, Navarro Chávez, Manuel, Gavilanes, Antonio W. D., Cedeño German, Roberto, and Chedraui, Peter
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Summary: We aimed at comparing the incidence of hip fractures in older adults from Ecuador before and during the COVID-19 pandemic. There was a significant reduction in the number of hip fractures, with no change in the length of hospital stay, mortality, and case-fatality rate, during the period of social isolation. Introduction: The impact that the COVID-19 pandemic has had on fragility fractures is being recently evaluated in the literature. Despite this, data from Latin America in this regard is scarce. Purpose: This study aims to compare the incidence rate of hip fractures before and during the COVID-19 pandemic in older adults who received care in the public and private health system of Ecuador. Methods: This was a descriptive and retrospective study that analyzed data of individuals aged 60 years and older who had hip fractures before and during the COVID-19 pandemic. The information was obtained from the National Hospital Discharge Yearbook. We calculated the incidence, average length of hospital stay, mortality, and case-fatality rate associated with hip fractures. Results: There was a significant reduction in the incidence of hip fractures in adults 60 or older during the period of social isolation due to COVID-19. Between March and December 2019, there was an incidence of 152 hip fractures per 100,000 inhabitants, whereas during the same period but in 2020 in the incidence was 110 per 100,000 inhabitants (p < 0.0001). The main decrease was observed in women aged 80 or more. The average length of hospital stay did not show significant changes. Mortality displayed a non-significant decrease (p = 0.14), although this decrease was significant among women (p = 0.02). Case-fatality rate showed a non-significant increase for the whole group (p = 0.68) and for men (p = 0.09). Conclusion: Hip fracture rates decreased significantly in adults aged 60 and older in 2020 compared to 2019. This decrease of hip fracture incidence rates was mainly due to the reductions observed in older people and women. The average length of hospital stay, mortality, and case-fatality rate associated with hip fractures did not show significant changes during the pandemic. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Increased Number of Cerebellar Granule Cells and Astrocytes in the Internal Granule Layer in Sheep Following Prenatal Intra-amniotic Injection of Lipopolysaccharide
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Strackx, Eveline, Gantert, Markus, Moers, Veronique, van Kooten, Imke A. J., Rieke, Rebecca, Hürter, Hanna, Lemmens, Marijke A. M., Steinbusch, Harry W. M., Zimmermann, L. J. I., Vles, Johannes S. H., Garnier, Yves, Gavilanes, Antonio W. D., and Kramer, Boris W.
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- 2012
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13. Periaqueductal Grey Stimulation Induced Panic-Like Behaviour Is Accompanied by Deactivation of the Deep Cerebellar Nuclei
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Moers-Hornikx, Véronique M. P., Vles, Johan S. H., Lim, Lee Wei, Ayyildiz, Mustafa, Kaplan, Sűleyman, Gavilanes, Antonio W. D., Hoogland, Govert, Steinbusch, Harry W. M., and Temel, Yasin
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- 2011
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14. Noninvasive Mechanical Ventilation with Average Volume-Assured Pressure Support versus BiPAP S/T in De Novo Hypoxemic Respiratory Failure.
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Briones-Claudett, Killen H., Briones-Claudett, Mónica H., Baños, Mariuxi del Pilar Cabrera, Briones Zamora, Killen H., Briones Marquez, Diana C., Zimmermann, Luc J. I., Gavilanes, Antonio W. D., and Grunauer, Michelle
- Abstract
Background: Bilevel positive airway pressure in spontaneous/time and average volume-assured pressure support (BiPAP·S/T-AVAPS) could maintain an adequate tidal volume by reducing the patient's inspiratory effort; however, this ventilatory strategy has not been compared with other ventilatory modes, especially the conventional BiPAP S/T mode, when noninvasive mechanical ventilation (NIMV) is used. The primary objective of this study was to determine the rate of success and failure of the use of BiPAP·S/T-AVAPS versus BiPAP·S/T alone in patients with mild-to-moderate "de novo" hypoxemic respiratory failure.Methods: This was a matched-cohort study. Subjects with mild-to-moderate de novo hypoxemic respiratory failure were divided into two groups according to the ventilatory strategy used. The subjects in the BiPAP·S/T group were paired with those in the BiPAP·S/T-AVAPS group.Results: A total of 58 subjects were studied. Twenty-nine subjects in the BiPAP·S/T group were paired with 29 subjects in the BiPAP·S/T-AVAPS group. Twenty patients (34.5%) presented with "failure of NIMV," while 38 (65.5%) patients did not. In addition, 13 (22.4%) patients died, while 45 (77.6%) recovered. No differences were found in the percentage of intubation (P=0.44) and mortality (P=0.1).Conclusion: The BiPAP S/T-AVAPS ventilator mode was not superior to the BiPAP·S/T mode. A high mortality rate was observed in patients with NIMV failure in both modes. This trial is registered with https://doi.org/10.1186/ISRCTN17904857. [ABSTRACT FROM AUTHOR]- Published
- 2022
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15. Apnea-Hypopnea Index in Chronic Obstructive Pulmonary Disease Exacerbation Requiring Noninvasive Mechanical Ventilation with Average Volume-Assured Pressure Support.
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Briones-Claudett, Killen H., Romero Lopez, Adela, Briones-Claudett, Mónica H., Cabrera Baños, Mariuxi del Pilar, Briones Zamora, Killen H., Briones Marquez, Diana C., Icaza-Freire, Andrea P., Zimmermann, Luc J. I., Gavilanes, Antonio W. D., and Grunauer, Michelle
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Introduction: This study intends to determine the Apnea-Hypopnea Index in patients hospitalized with acute hypercapnic respiratory failure from chronic obstructive pulmonary disease exacerbation, who require noninvasive ventilation with average volume-assured pressure support (AVAPS), as well as describes the clinical characteristics of these patients.Materials and Methods: We designed a single-center prospective study. The coexistence of Apnea-Hypopnea Index and clinical, gasometric, spirometric, respiratory polygraphy, and ventilatory characteristics were determined. The clinical characteristics found were categorized and compared according to the Apnea-Hypopnea Index (AHI) < 5, AHI 5-15, and AHI >15. A p value <0.05 was considered statistically significant.Results: During the study period, a total of 100 patients were admitted to the ICU with a diagnosis of acute hypercapnic respiratory failure due to COPD exacerbation. 72 patients presented with acute respiratory failure and fulfilled criteria for ventilatory support. Within them, 24 received invasive mechanical ventilation and 48 NIV. After applying the inclusion criteria for this study, 30 patients were eligible. An AHI >5 was present in 24 of the 30 patients recruited (80%). Neck circumference (cm), Epworth scale, and Mallampati score evidenced significant differences when compared to the patient's AHI <5, AHI 5-15, and AHI >15 (p < 0.05). Furthermore, patients with an AHI >5 had longer hospital admissions, prolonged periods on mechanical ventilation, and a higher percentage of intubation rates.Conclusion: Apnea-Hypopnea Index and chronic obstructive pulmonary disease exacerbation are a frequent association found in patients with acute hypercapnic respiratory failure and COPD exacerbations that require NIV. This association could be a determining factor in the response to NIV, especially when AVAPS is used as a ventilatory strategy. [ABSTRACT FROM AUTHOR]- Published
- 2021
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16. Statistical differences resulting from selection of stable reference genes after hypoxia and hypothermia in the neonatal rat brain.
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Bustelo, Martín, Bruno, Martín A., Loidl, César F., Rey-Funes, Manuel, Steinbusch, Harry W. M., Gavilanes, Antonio W. D., and van den Hove, D. L. A.
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GENE expression profiling ,GENE expression ,HYPOXEMIA ,CEREBRAL anoxia ,HYPOTHERMIA ,NEONATAL sepsis - Abstract
Real-time reverse transcription PCR (qPCR) normalized to an internal reference gene (RG), is a frequently used method for quantifying gene expression changes in neuroscience. Although RG expression is assumed to be constant independent of physiological or experimental conditions, several studies have shown that commonly used RGs are not expressed stably. The use of unstable RGs has a profound effect on the conclusions drawn from studies on gene expression, and almost universally results in spurious estimation of target gene expression. Approaches aimed at selecting and validating RGs often make use of different statistical methods, which may lead to conflicting results. Based on published RG validation studies involving hypoxia the present study evaluates the expression of 5 candidate RGs (Actb, Pgk1, Sdha, Gapdh, Rnu6b) as a function of hypoxia exposure and hypothermic treatment in the neonatal rat cerebral cortex–in order to identify RGs that are stably expressed under these experimental conditions–using several statistical approaches that have been proposed to validate RGs. In doing so, we first analyzed RG ranking stability proposed by several widely used statistical methods and related tools, i.e. the Coefficient of Variation (CV) analysis, GeNorm, NormFinder, BestKeeper, and the ΔCt method. Using the Geometric mean rank, Pgk1 was identified as the most stable gene. Subsequently, we compared RG expression patterns between the various experimental groups. We found that these statistical methods, next to producing different rankings per se, all ranked RGs displaying significant differences in expression levels between groups as the most stable RG. As a consequence, when assessing the impact of RG selection on target gene expression quantification, substantial differences in target gene expression profiles were observed. Altogether, by assessing mRNA expression profiles within the neonatal rat brain cortex in hypoxia and hypothermia as a showcase, this study underlines the importance of further validating RGs for each individual experimental paradigm, considering the limitations of the statistical methods used for this aim. [ABSTRACT FROM AUTHOR]
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- 2020
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17. The use of information and communication technologies in Latin American dentists: a cross-sectional study from Ecuador.
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Chérrez-Ojeda, Ivan, Vera, Carlos, Vanegas, Emanuel, Gallardo, Juan Carlos, Felix, Miguel, Espinoza-Fuentes, Fernando, Chedraui, Peter, Gavilanes, Antonio W. D., and Mata, Valeria L.
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CHI-squared test ,CONTINUING education ,DENTAL education ,PSYCHOLOGY of dentists ,INFORMATION technology ,INTERPROFESSIONAL relations ,MEDICAL ethics ,PRIVACY ,QUESTIONNAIRES ,STATISTICS ,SURVEYS ,TELECOMMUNICATION ,PEER relations ,SOCIAL media ,CROSS-sectional method ,INTERNET access - Abstract
Background: The use of information and communication technologies (ICTs) provide the tools for enabling fast and reliable real-time communications, as well as the transfer of information between dental professionals and their patients. However, little is known about the frequency and preference of ICTs among Latin-American dentists. Our study aims to fill this gap by assessing different aspects related to ICTs, mainly the frequency of use, perceptions, and barriers among Ecuadorian dentists. Methods: An anonymous, cross-sectional survey-based study was conducted among 342 Ecuadorian dentists. The final questionnaire included 13 items related to the frequency of use, perceptions, and barriers of ICTs. Bivariate analysis was performed by using chi-squared testing to explore the association between the independent variables and the intended use of ICTs, as well as to characterize the perceptions and barriers related to ICTs. Results: In general, most participants reported the use of ICTs to communicate with colleagues (99.7%), and patients (96.2%), while only 63.5% reported using ICTs to obtain academic information in their daily practice. WhatsApp was rated as the most used ICT for communicating with colleagues and patients. A majority of participants considered that ICTs can be useful for facilitating continuing dental education (92.1%), searching new work opportunities (91.5%), promoting health (90.1%), working with colleagues and other health professionals (91.2%), promoting their professional services (90.6%), and for resolving clinical cases (87.7%). On the subject of barriers, privacy and security concerns about personal and/or patient information was the biggest concern among dentists (65%), followed by lack of time to learn how to use and/or use ICTs (48%), lack of mobile internet access (28.1%), and lack of internet access at work (24.9%). Conclusion: In our study, we found that Ecuadorian dentists had a high usage rate of ICTs, mainly for communicating with other colleagues and patients, while the academic use of technology remains a comparatively underused application. Most of the participants surveyed had a positive perception towards ICTs, while privacy and security concerns were identified as the main barrier. Older age was associated with a less favourable perception toward ICTs, as well as an increased likelihood of reporting barriers related to the use of technology. [ABSTRACT FROM AUTHOR]
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- 2020
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18. Polymorphism of the THOC5 of the transcription/export multiprotein complex and its correlation with the lipid and metabolic profile in middle-aged women.
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Loja-Chango, Rita, Salazar-Pousada, Danny, Escobar-Valdivieso, Gustavo S., Ramírez-Morán, Cecibel, Espinoza-Caicedo, Jasson, Pérez-López, Faustino R., Gavilanes, Antonio W. D., and Chedraui, Peter
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MIDDLE-aged women ,LIPIDS ,MESSENGER RNA ,BLOOD lipids ,METABOLIC syndrome ,TRANSGENIC organisms - Abstract
Copyright of Gynecological Endocrinology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2020
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19. Comparison of three non-invasive ventilation strategies (NSIPPV/BiPAP/NCPAP) for RDS in VLBW infants.
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Salvo, Vincenzo, Lista, Gianluca, Lupo, Enrica, Ricotti, Alberto, Zimmermann, Luc J. I., Gavilanes, Antonio W. D., Gitto, Eloisa, Colivicchi, Micaela, Ferraù, Valeria, and Gazzolo, Diego
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BIRTH weight ,NEONATAL diseases ,RETROSPECTIVE studies ,NONINVASIVE ventilation ,RESPIRATORY distress syndrome - Abstract
Background: Non-invasive ventilation (NIV) significantly changed the management of respiratory distress syndrome (RDS) in preterm infants. Further perspectives for neonatologists regard the assessment of different NIV strategies in terms of availability, effectiveness, and failure. Objective: The aim of the present study is to evaluate the effectiveness of three different NIV strategies: nasal continuous positive airway pressure (N-CPAP), nasal synchronized intermittent positive pressure ventilation (N-SIPPV), and nasal bilevel-CPAP (BiPAP), as first intention treatment for RDS in very low birth-weight infants (VLBW). Methods: A multicenter retrospective study was conducted in three neonatal intensive care unit (NICUs) that enrolled 191 VLBW infants complicated by RDS, who received, as first intention treatment for RDS, three different NIV approaches (N-CPAP: n = 66; N-SIPPV: n = 62, BiPAP: n = 63). We evaluated the performance of different NIV strategies by primary (failure within the first 5 d of life) and some selected secondary end-points. Results: The incidence of NIV failure was significantly higher in the N-CPAP group (22/66) versus N-SIPPV/BiPAP groups (11/62; 11/63) (p < .05 for both), while no difference was observed between N-SIPPV and BiPAP groups. Moreover, no differences were found between the three groups regarding secondary outcomes. Conclusions: The present study shows that first intention N-SIPPV/BiPAP, as NIV support, augment the beneficial effects of N-CPAP contributing to a reduced risk of failure in VLBW infants complicated by RDS. Data open up to further RCTs on a wider population to evaluate NIV effectiveness on long-term outcomes. [ABSTRACT FROM AUTHOR]
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- 2018
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20. Comparison of three non-invasive ventilation strategies (NSIPPV/BiPAP/NCPAP) for RDS in VLBW infants.
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Salvo, Vincenzo, Lista, Gianluca, Lupo, Enrica, Ricotti, Alberto, Zimmermann, Luc J I, Gavilanes, Antonio W D, Gitto, Eloisa, Colivicchi, Micaela, Ferraù, Valeria, and Gazzolo, Diego
- Abstract
Background: Non-invasive ventilation (NIV) significantly changed the management of respiratory distress syndrome (RDS) in preterm infants. Further perspectives for neonatologists regard the assessment of different NIV strategies in terms of availability, effectiveness, and failure.Objective: The aim of the present study is to evaluate the effectiveness of three different NIV strategies: nasal continuous positive airway pressure (N-CPAP), nasal synchronized intermittent positive pressure ventilation (N-SIPPV), and nasal bilevel-CPAP (BiPAP), as first intention treatment for RDS in very low birth-weight infants (VLBW).Methods: A multicenter retrospective study was conducted in three neonatal intensive care unit (NICUs) that enrolled 191 VLBW infants complicated by RDS, who received, as first intention treatment for RDS, three different NIV approaches (N-CPAP: n = 66; N-SIPPV: n = 62, BiPAP: n = 63). We evaluated the performance of different NIV strategies by primary (failure within the first 5 d of life) and some selected secondary end-points.Results: The incidence of NIV failure was significantly higher in the N-CPAP group (22/66) versus N-SIPPV/BiPAP groups (11/62; 11/63) (p < .05 for both), while no difference was observed between N-SIPPV and BiPAP groups. Moreover, no differences were found between the three groups regarding secondary outcomes.Conclusions: The present study shows that first intention N-SIPPV/BiPAP, as NIV support, augment the beneficial effects of N-CPAP contributing to a reduced risk of failure in VLBW infants complicated by RDS. Data open up to further RCTs on a wider population to evaluate NIV effectiveness on long-term outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2017
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21. Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy - where to from here?
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Davidson, Joanne O., Wassink, Guido, van den Heuij, Lotte G., Bennet, Laura, Gunn, Alistair J., Baburamani, Ana A., and Gavilanes, Antonio W. Danilo
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THERAPEUTIC hypothermia ,NEUROLOGICAL disorders ,CEREBRAL ischemia - Abstract
Hypoxia-ischemia before or around the time of birth occurs in approximately 2/1000 live births and is associated with a high risk of death or lifelong disability. Therapeutic hypothermia is now well established as standard treatment for infants with moderate to severe hypoxic-ischemic encephalopathy but is only partially effective. There is compelling preclinical and clinical evidence that hypothermia is most protective when it is started as early as possible after hypoxia-ischemia. Further improvements in outcome from therapeutic hypothermia are very likely to arise from strategies to reduce the delay before starting treatment of affected infants. In this review, we examine evidence that current protocols are reasonably close to the optimal depth and duration of cooling, but that the optimal rate of rewarming after hypothermia is unclear. The potential for combination treatments to augment hypothermic neuroprotection has considerable promise, particularly with endogenous targets such as melatonin and erythropoietin, and noble gases such as xenon. We dissect the critical importance of preclinical studies using realistic delays in treatment and clinically relevant cooling protocols when examining combination treatment, and that for many strategies overlapping mechanisms of action can substantially attenuate any effects. [ABSTRACT FROM AUTHOR]
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- 2015
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22. Intra-Amniotic LPS Induced Region-Specific Changes in Presynaptic Bouton Densities in the Ovine Fetal Brain.
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Strackx, Eveline, Jellema, Reint K., Rieke, Rebecca, Gussenhoven, Ruth, Vles, Johan S. H., Kramer, Boris W., and Gavilanes, Antonio W. D.
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FETAL brain ,INFLAMMATION ,AMNIOTIC liquid ,INFECTION ,IMMUNOHISTOCHEMISTRY ,SYNAPTOPHYSIN ,DENTATE gyrus ,HIPPOCAMPUS (Brain) - Abstract
Rationale. Chorioamnionitis has been associated with increased risk for fetal brain damage. Although, it is now accepted that synaptic dysfunction might be responsible for functional deficits, synaptic densities/numbers after a fetal inflammatory challenge have not been studied in different regions yet. Therefore, we tested in this study the hypothesis that LPS-induced chorioamnionitis caused profound changes in synaptic densities in different regions of the fetal sheep brain. Material and Methods. Chorioamnionitis was induced by a 10 mg intra-amniotic LPS injection at two different exposure intervals. The fetal brain was studied at 125 days of gestation (term = 150 days) either 2 (LPS2D group) or 14 days (LPS14D group) after LPS or saline injection (control group). Synaptophysin immunohistochemistry was used to quantify the presynaptic density in layers 2-3 and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and dentate gyrus of the hippocampus. Results. There was a significant reduction in presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to control animals. Only in the motor cortex and putamen, the presynaptic density was significantly decreased in the LPS14 D compared to the control group. No changes were found in the dentate gyrus of the hippocampus and the piriforme cortex. Conclusion. We demonstrated that LPS-induced chorioamnionitis caused a decreased density in presynaptic boutons in different areas in the fetal brain. These synaptic changes seemed to be region-specific, with some regions being more affected than others, and seemed to be transient in some regions. [ABSTRACT FROM AUTHOR]
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- 2015
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23. Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in the placenta of pregnancies complicated with preeclampsia.
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Chedraui, Peter, Andrade, Mariela E., Salazar-Pousada, Danny, Escobar, Gustavo S., Hidalgo, Luis, Ramirez, Cecibel, Spaanderman, Marc E. A., Kramer, Boris W., and Gavilanes, Antonio W. D.
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PREECLAMPSIA ,SINGLE nucleotide polymorphisms ,GENETIC polymorphisms ,METHYLENETETRAHYDROFOLATE reductase ,PLACENTA - Abstract
Background: Preeclampsia has been related to single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate reductase (MTHFR) gene; however, data regarding the placenta are still lacking. Objective: To determine the frequency of C677T and A1298C SNPs of the MTHFR gene in the placenta of preeclamptic pregnancies and healthy controls. Methods: Genotyping of C677T and A1298C polymorphisms of the MTHFR gene using RFLP-PCR was performed to the placenta of 100 gestations (n = 50 complicated with preeclampsia andn = 50 normal controls matched for parity and maternal age). Results: Gestational age at birth and neonatal and placental weight were significantly lower in women with preeclampsia as compared to controls. The TT genotype of the C677T polymorphism was threefold more prevalent in preeclamptic placentas as compared to the placenta of controls (24.0% versus 8.0%,p = 0.001). Upon pooled analysis (n = 100), placental and neonatal weights were significantly lower in placentas displaying this genotype (TT, C677T) as compared with the CC genotype. Conclusion: This study found that the frequency of the TT mutant genotype of the C677T polymorphism was higher in the placenta of pregnancies complicated with preeclampsia. There is a need for further research in this matter. [ABSTRACT FROM AUTHOR]
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- 2015
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24. Noninvasive Ventilation Strategies for Early Treatment of RDS in Preterm Infants: An RCT.
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Salvo, Vincenzo, Lista, Gianluca, Lupo, Enrica, Ricotti, Alberto, Zimmermann, Luc J. I., Gavilanes, Antonio W. D., Barberi, Ignazio, Colivicchi, Micaela, Temporini, Francesca, and Gazzolo, Diego
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- 2015
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25. Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.
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Cox-Limpens, Kimberly E. M., Vles, Johan S. H., van den Hove, Daniel L. A., Zimmermann, Luc J. I., and Gavilanes, Antonio W. D.
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ASPHYXIA neonatorum ,NEUROPROTECTIVE agents ,GENETIC transcription ,NEONATAL diseases ,UNIVARIATE analysis ,GENETICS ,THERAPEUTICS - Abstract
Background Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates. Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditioning (FAPA). Offspring were sacrificed 6 h and 96 h after birth, and wholegenome transcription was investigated using the Affymetrix Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma package. In addition to univariate analysis, we performed Gene Set Enrichment Analysis (GSEA) in order to derive results with maximum biological relevance. Results We observed minimal, 25% or less, overlap of differentially regulated transcripts across different experimental groups which leads us to conclude that the transcriptional phenotype of these groups is largely unique. In both the PA and FAPA group we observe an upregulation of transcripts involved in cellular stress. Contrastingly, transcripts with a function in the cell nucleus were mostly downregulated in PA animals, while we see considerable upregulation in the FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are exclusively regulated in FAPA animals. Conclusions This study is the first to investigate whole-genome transcription in the neonatal brain after PA alone, and after perinatal asphyxia preceded by preconditioning (FAPA). We describe several genes/pathways, such as ubiquitination and proteolysis, which were not previously linked to preconditioning-induced neuroprotection. Furthermore, we observed that the majority of upregulated genes in preconditioned animals have a function in the cell nucleus, including several epigenetic players such as HDACs, which suggests that epigenetic mechanisms are likely to play a role in preconditioning-induced neuroprotection. [ABSTRACT FROM AUTHOR]
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- 2014
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26. N-SIPPV versus bi-level N-CPAP for early treatment of respiratory distress syndrome in preterm infants.
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Ricotti, Alberto, Salvo, Vincenzo, Zimmermann, Luc J. I., Gavilanes, Antonio W. D., Barberi, Ignazio, Lista, Gianluca, Colivicchi, Micaela, Temporini, Francesca, and Gazzolo, Diego
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LOW birth weight ,RESPIRATORY distress syndrome treatment ,ARTIFICIAL respiration ,RETROSPECTIVE studies ,APNEA treatment ,CONTINUOUS positive airway pressure - Abstract
Objective: Non-invasive ventilation (NIV) for RDS in extremely/very low birth-weight infants represents the new challenge for neonatologists. In this regard, data comparing the effectiveness of Bi-Level-NCPAP (BiPAP) versus nasal synchronized intermittent positive pressure ventilation (NSIPPV) as primary mode of treatment for RDS are lacking. Study design: We conducted a retrospective study from December 2007 to December 2010 in seventy-eight infants, who received NIV (N-SIPPV: 33; BiPAP: 45). The primary outcomes were the length and failure of NIV. Secondary outcomes were adverse short-long term pulmonary outcomes, multiple doses of surfactant and others. Results: There were no significant differences ( p > 0.05) between the two different NIV modes. Conclusion: The present findings suggest that N-SIPPV and BiPAP gives similar results in the RDS treatment. We did not find a benefit of one over the other ventilation mode and both could be constitute a valid option to conventional mechanical ventilation. The theoretical benefits of these two different methods of NIV are tidal volume enhancement, improvements of the functional residual capacity and of the mean airway pressure and reducing apnea episodes. Further randomized studies to assess the advantages and the efficacy of different methods of NIV for the treatment of the RDS are needed. [ABSTRACT FROM AUTHOR]
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- 2013
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27. Fetal brain genomic reprogramming following asphyctic preconditioning.
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Cox-Limpens, Kimberly E. M., Vles, Johan S. H., Schlechter, Jana, Zimmermann, Luc J. I., Strackx, Eveline, and Gavilanes, Antonio W. D.
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FETAL brain ,BRAIN damage ,GENOMICS ,GENE expression ,NEURAL transmission ,GENETIC transcription - Abstract
Background: Fetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore we investigated whole genome differential gene expression in the preconditioned rat brain. FA preconditioning was induced on embryonic day 17 by reversibly clamping uterine circulation. Male control and FA offspring were sacrificed 96 h after FA preconditioning. Whole genome transcription was investigated with Affymetrix Gene1.0ST chip. Results: Data were analyzed with the Bioconductor Limma package, which showed 53 down-regulated and 35 up-regulated transcripts in the FA-group. We validated these findings with RT-qPCR for adh1, edn1, leptin, rdh2, and smad6. Moreover, we investigated differences in gene expression across different brain regions. In addition, we performed Gene Set Enrichment Analysis (GSEA) which revealed 19 significantly down-regulated gene sets, mainly involved in neurotransmission and ion transport. 10 Gene sets were significantly up-regulated, these are mainly involved in nucleosomal structure and transcription, including genes such as mecp2. Conclusions: Here we identify for the first time differential gene expression after asphyctic preconditioning in fetal brain tissue, with the majority of differentially expressed transcripts being down-regulated. The observed down-regulation of cellular processes such as neurotransmission and ion transport could represent a restriction in energy turnover which could prevent energy failure and subsequent neuronal damage in an asphyctic event. Up-regulated transcripts seem to exert their function mainly within the cell nucleus, and subsequent Gene Set Enrichment Analysis suggests that epigenetic mechanisms play an important role in preconditioning induced neuroprotection. [ABSTRACT FROM AUTHOR]
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- 2013
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28. Cerebral inflammation and mobilization of the peripheral immune system following global hypoxia-ischemia in preterm sheep.
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Jellema, Reint K., Passos, Valéria Lima, Zwanenburg, Alex, Ophelders, Daan RMG, De Munter, Stephanie, Vanderlocht, Joris, Germeraad, Wilfred TV, Kuypers, Elke, Collins, Jennifer J. P., Cleutjens, Jack P. M., Jennekens, Ward, Gavilanes, Antonio W. D., Seehase, Matthias, Vles, Hans J., Steinbusch, Harry, Andriessen, Peter, Wolfs, Tim GAM, and Kramer, Boris W.
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INFLAMMATION ,IMMUNE system ,HYPOXEMIA ,ISCHEMIA ,BRAIN injuries ,PREMATURE infants ,SHEEP as laboratory animals - Abstract
Background: Hypoxic-ischemic encephalopathy (HIE) is one of the most important causes of brain injury in preterm infants. Preterm HIE is predominantly caused by global hypoxia-ischemia (HI). In contrast, focal ischemia is most common in the adult brain and known to result in cerebral inflammation and activation of the peripheral immune system. These inflammatory responses are considered to play an important role in the adverse outcomes following brain ischemia. In this study, we hypothesize that cerebral and peripheral immune activation is also involved in preterm brain injury after global HI. Methods: Preterm instrumented fetal sheep were exposed to 25 minutes of umbilical cord occlusion (UCO) (n = 8) at 0.7 gestation. Sham-treated animals (n = 8) were used as a control group. Brain sections were stained for ionized calcium binding adaptor molecule 1 (IBA-1) to investigate microglial proliferation and activation. The peripheral immune system was studied by assessment of circulating white blood cell counts, cellular changes of the spleen and influx of peripheral immune cells (MPO-positive neutrophils) into the brain. Pre-oligodendrocytes (preOLs) and myelin basic protein (MBP) were detected to determine white matter injury. Electro-encephalography (EEG) was recorded to assess functional impairment by interburst interval (IBI) length analysis. Results: Global HI resulted in profound activation and proliferation of microglia in the hippocampus, periventricular and subcortical white matter. In addition, non-preferential mobilization of white blood cells into the circulation was observed within 1 day after global HI and a significant influx of neutrophils into the brain was detected 7 days after the global HI insult. Furthermore, global HI resulted in marked involution of the spleen, which could not be explained by increased splenic apoptosis. In concordance with cerebral inflammation, global HI induced severe brain atrophy, region-specific preOL vulnerability, hypomyelination and persistent suppressed brain function. Conclusions: Our data provided evidence that global HI in preterm ovine fetuses resulted in profound cerebral inflammation and mobilization of the peripheral innate immune system. These inflammatory responses were paralleled by marked injury and functional loss of the preterm brain. Further understanding of the interplay between preterm brain inflammation and activation of the peripheral immune system following global HI will contribute to the development of future therapeutic interventions in preterm HIE. [ABSTRACT FROM AUTHOR]
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- 2013
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29. Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats.
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Vlassaks, Evi, Strackx, Eveline, Vles, Johan S. H., Nikiforou, Maria, Martinez-Martinez, Pilar, Kramer, Boris W., and Gavilanes, Antonio W. D.
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CYTOKINE receptors ,ASPHYXIA neonatorum ,LABORATORY rats ,BRAIN damage ,NEURODEVELOPMENTAL treatment ,PHENOTYPES ,INFLAMMATION ,INTERLEUKIN-6 - Abstract
Background: Perinatal asphyxia (PA) is a major cause of brain damage and neurodevelopmental impairment in infants. Recent investigations have shown that experimental sublethal fetal asphyxia (FA preconditioning) protects against a subsequent more severe asphyctic insult at birth. The molecular mechanisms of this protection have, however, not been elucidated. Evidence implicates that inflammatory cytokines play a protective role in the induction of ischemic tolerance in the adult brain. Accordingly, we hypothesize that FA preconditioning leads to changes in the fetal cytokine response, thereby protecting the newborn against a subsequent asphyctic insult. Methods: In rats, FA preconditioning was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global PA was induced by placing the uterine horns, containing the pups, in a saline bath for 19 min. We assessed, at different time points after FA and PA, mRNA and protein expression of several cytokines and related receptor mRNA levels in total hemispheres of fetal and neonatal brains. Additionally, we measured pSTAT3/STAT3 levels to investigate cellular responses to these cytokines. Results: Prenatally, FA induced acute downregulation in IL-1ß, TNF-a and IL-10 mRNA levels. At 96 h post FA, IL-6 mRNA and IL-10 protein expression were increased in FA brains compared with controls. Two hours after birth, all proinflammatory cytokines and pSTAT3/STAT3 levels decreased in pups that experienced FA and/or PA. Interestingly, IL-10 and IL-6 mRNA levels increased after PA. When pups were FA preconditioned, however, IL-10 and IL-6 mRNA levels were comparable to those in controls. Conclusions: FA leads to prenatal changes in the neuroinflammatory response. This modulation of the cytokine response probably results in the protective inflammatory phenotype seen when combining FA and PA and may have significant implications for preventing post-asphyctic perinatal encephalopathy. [ABSTRACT FROM AUTHOR]
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- 2013
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30. Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs.
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Kuypers, Elke, Collins, Jennifer J. P., Kramer, Boris W., Ofman, Gaston, Nitsos, Ilias, Pillow, J. Jane, Polglase, Graeme R., Kemp, Matthew W., Newnham, John P., Gavilanes, Antonio W. D., Nowacki, Relana, Ikegami, Machiko, Jobe, Alan H., and Kallapur, Suhas G.
- Abstract
The proinflammatory stimulus of chorioamnionitis is commonly associated with preterm delivery. Women at risk of preterm delivery receive antenatal glucocorticoids to functionally mature the fetal lung. However, the effects of the combined exposures of chorioamnionitis and antenatal glucocorticoids on the fetus are poorly understood. Time-mated ewes with singleton fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) either preceding or following maternal intramuscular betamethasone 7 or 14 days before delivery, and the fetuses were delivered at 120 days gestational age (GA) (term = 150 days GA). Gestation matched controls received intra-amniotic and maternal intramuscular saline. Compared with saline controls, intra-amniotic LPS increased inflammatory cells in the bronchoalveolar lavage and myeloperoxidase, Toll-like receptor 2 and 4 mRNA, PU.1, CD3, and Foxp3-positive cells in the fetal lung. LPS-induced lung maturation measured as increased airway surfactant and improved lung gas volumes. Intra-amniotic LPS-induced inflammation persisted until 14 days after exposure. Betamethasone treatment alone induced modest lung maturation but, when administered before intra-amniotic LPS, suppressed lung inflammation. Interestingly, betamethasone treatment after LPS did not counteract inflammation but enhanced lung maturation. We conclude that the order of exposures of intra-amniotic LPS or maternal betamethasone had large effects on fetal lung inflammation and maturation. [ABSTRACT FROM AUTHOR]
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- 2012
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31. First intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis.
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Salvo, Vincenzo, Zimmermann, Luc J, Gavilanes, Antonio W, Barberi, Ignazio, Ricotti, Alberto, Abella, Raul, Frigiola, Alessandro, Giamberti, Alessandro, Florio, Pasquale, Tagliabue, Paolo, Tina, Lucia G, Nigro, Francesco, Temporini, Francesca, and Gazzolo, Diego
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- 2012
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32. Use of neonatal intensive care unit as a safe place for neonatal surgery.
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Gavilanes, Antonio W. D., Heineman, Erik, Herpers, Marcel J. H. M., and Blanco, Carlos E.
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- 1997
33. New FRAX-based intervention and assessment thresholds for the Ecuadorian population.
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Lopez Gavilanez, Enrique, Gavilanes, Antonio W. D., Chedraui, Peter, and Segale Bajaña, Angel
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- 2018
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34. Biomarkers of Brain Function and Injury: Biological and Clinical Significance.
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Gazzolo, Diego, Li Volti, Giovanni, Gavilanes, Antonio W. D., and Scapagnini, Giovanni
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BIOMARKERS ,ASPHYXIA neonatorum ,METABOLOMICS - Abstract
An introduction is presented in which the editor discusses various reports within the issue on topics including research studies on biomarkers assessment under different brain damage conditions, a sheep-based research study of perinatal asphyxia, and metabolomics patterns in intrauterine restricted newborns.
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- 2015
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35. White matter injury following fetal inflammatory response syndrome induced by chorioamnionitis and fetal sepsis: Lessons from experimental ovine models
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Kuypers, Elke, Ophelders, Daan, Jellema, Reint K., Kunzmann, Steffen, Gavilanes, Antonio W., and Kramer, Boris W.
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- *
FETAL brain , *BRAIN injuries , *NEURODEVELOPMENTAL treatment for infants , *CLINICAL trials , *COGNITION disorders , *ANIMAL models in research - Abstract
Abstract: Chorioamnionitis and fetal sepsis can induce a fetal inflammatory response syndrome (FIRS) which is closely related to the development of white matter injury in the fetal brain. Large epidemiological studies support the link between FIRS and fetal brain injury with a clear association between the presence of in utero inflammation and neurodevelopmental complications such as cerebral palsy, autism and cognitive impairments later in life. Translational animal models of chorioamnionitis and fetal sepsis are essential in understanding the underlying pathophysiological mechanisms of fetal brain injury after exposure to intra-uterine inflammation. Concerning this aspect, ovine models have high translational value since neurodevelopment in sheep closely resembles the human situation. In this article, we will review clinical and experimental evidence for the link between FIRS and white matter injury in the fetal brain. With respect to experimental findings, we will particularly focus on the lessons learned from ovine models of chorioamnionitis and fetal sepsis. We also highlight two key players implied in the pathophysiology of white matter injury after in utero exposure to inflammation. [Copyright &y& Elsevier]
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- 2012
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36. Understanding Post-COVID-19: Mechanisms, Neurological Complications, Current Treatments, and Emerging Therapies.
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Zambrano K, Castillo K, Peñaherrera S, Vasconez HC, Caicedo A, and Gavilanes AWD
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COVID-19, a highly infectious disease, caused a worldwide pandemic in early 2020. According to the World Health Organization (WHO), COVID-19 has resulted in approximately 774 million cases and around 7 million deaths. The effects of COVID-19 are well known; however, there is a lack of information on the pathophysiological mechanisms underlying the symptoms that comprise Post-Acute COVID-19 Syndrome (PACS) or Long COVID-19. Neurological sequelae are common, with cognitive dysfunction being one of the foremost symptoms. Research indicates that elevated inflammatory levels and increased oxidative stress may play a role in the etiology and severity of PACS. Treatment options are extremely limited, and there is no consensus among the medical and scientific communities on how to manage the disease. Nevertheless, many scientists advocate for using antioxidants for symptomatic therapy and cognitive behavior therapy for supportive care. Additionally, current research aims to ameliorate several aspects of the inflammatory cascade. This review highlights the intracellular and extracellular pathways crucial to the neurological manifestations of PACS, providing valuable information for healthcare professionals and scientists. Given the complex nature of PACS, understanding these pathways is essential for developing new treatment options. Assessing PACS is challenging, and reviewing current therapeutic options while proposing a triad of potential therapeutic elements will add value to clinical assays and guidelines. Current therapeutic strategies, such as antioxidants/vitamin supplements, neurogenic stem cell therapy, and mitochondrial therapy, could be combined to enhance their effectiveness. Future research should focus on validating these approaches and exploring new avenues for the effective treatment of PACS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Andrés Caicedo is the scientific founder and advisor of Dragon Biomed, an entrepreneurial initiative at the Universidad San Francisco de Quito (USFQ). He also serves as a scientific advisor in the Research and Development department of Luvigix. In these roles, he provides scientific guidance and expertise but does not participate in the decision-making processes or operational activities of either company., (© 2024 Zambrano et al.)
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- 2024
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37. Prevalence of menopausal symptoms and severity related factors among mid-aged Paraguayan women as measured with the 10-item Cervantes Scale.
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Sánchez-Zarza SC, Armeni AK, Chedraui P, Pérez-López FR, and Gavilanes AWD
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- Pregnancy, Female, Humans, Middle Aged, Child, Paraguay, Prevalence, Cross-Sectional Studies, Hot Flashes epidemiology, Surveys and Questionnaires, Menopause physiology, Sexual Behavior
- Abstract
Objective: To determine the prevalence of menopausal symptoms and factors related to severity in mid-aged women. Methods: Cross-sectional study in which 216 urban-living women from Asunción-Paraguay (40-60 years) were surveyed with the 10 item Cervantes Scale (CS-10) and a general questionnaire (personal and partner data). Results: Median (interquartile range [IQR]) age of the sample was 48 [9] years, 48.1% were postmenopausal, 8.8% used menopausal hormone therapy, 39.4% psychotropic drugs, 43.5% had hypertension, 6.5% diabetes, 51.9% abdominal obesity, and 89.3% had a partner ( n = 193). A history of sexual abuse was present in 2.8%. Median total CS-10 score was 8.5 [9.75]. Overall, 93.3% (180/193) of women having a partner were sexually active, with a median coital frequency of 8 times per month. According to the CS-10, the three most prevalent menopausal symptoms were: aching in muscles and/or joints (70.8%), anxiety and nervousness (70.8%) and hot flashes/night sweats (54.2%). Factors associated with higher CS-10 scores were: female age and educational level, marital status, menopausal status, and marital sexual aspects. Partner educational level was inversely correlated (rho Spearman coefficient) with CS-10 total scores. However, multiple linear regression analysis found that higher total CS-10 scores (more severe menopausal symptoms) negatively correlated to coital frequency and positively correlated with peri- and postmenopausal status, parity, sedentary lifestyle and a history of sexual abuse. Conclusion: Menopausal symptoms in this mid-aged urban female Paraguayan sample were related to hormonal, sexual and other female aspects.
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- 2023
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38. Divergent metabolic phenotypes in two genetic syndromes of low insulin secretion.
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Guevara-Aguirre J, Rosenbloom AL, Guevara A, Atkinson MA, Williams MD, Terán E, Posgai AL, Guevara C, Rosado V, Gavilanes AWD, and Wasserfall CH
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- Humans, Insulin Secretion, Syndrome, Insulin, Glucose, Islet Amyloid Polypeptide metabolism, Phenotype, Insulin-Like Growth Factor I metabolism, Adiponectin, Human Growth Hormone metabolism
- Abstract
Aims: We examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS)., Methods: Adults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP)., Results: Both syndromic cohorts displayed DIS during OGTT. LS subjects had higher serum concentrations of total and HMW adiponectin, and lower levels of IGF-I, IGF-II, and IGF-Binding Protein-3 than individuals in other study groups. Furthermore, they displayed normal glycemic responses during OGTT with the lowest IAPP secretion. In contrast, individuals with GRS had higher levels of protein glycation, deficient glucose control during OGTT, and increased secretion of IAPP., Conclusions: A distinct metabolic phenotype depending on GH counter-regulatory status, associates with diabetes development and excess glucose-induced IAPP secretion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)
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- 2023
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39. A new hope: Mitochondria, a critical factor in the war against prions.
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Zambrano K, Barba D, Castillo K, Robayo P, Arizaga E, Caicedo A, and Gavilanes AWD
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- Animals, Antioxidants, Cattle, Female, Mitochondria pathology, Prion Proteins, Encephalopathy, Bovine Spongiform, Prion Diseases pathology, Prions
- Abstract
Prion diseases encompass a group of incurable neurodegenerative disorders that occur due to the misfolding and aggregation of infectious proteins. The most well-known prion diseases are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (also known as mad cow disease), and kuru. It is estimated that around 1-2 persons per million worldwide are affected annually by prion disorders. Infectious prion proteins propagate in the brain, clustering in the cells and rapidly inducing tissue degeneration and death. Prion disease alters cell metabolism and energy production damaging mitochondrial function and dynamics leading to a fast accumulation of damage. Dysfunction of mitochondria could be considered as an early precursor and central element in the pathogenesis of prion diseases such as in sporadic CJD. Preserving mitochondria function may help to resist the rapid spread and damage of prion proteins and even clearance. In the war against prions and other degenerative diseases, studying how to preserve the function of mitochondria by using antioxidants and even replacing them with artificial mitochondrial transfer/transplant (AMT/T) may bring a new hope and lead to an increase in patients' survival. In this perspective review, we provide key insights about the relationship between the progression of prion disease and mitochondria, in which understanding how protecting mitochondria function and viability by using antioxidants or AMT/T may help to develop novel therapeutic interventions., (Copyright © 2022 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
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- 2022
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40. Fighting Parkinson's disease: The return of the mitochondria.
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Zambrano K, Barba D, Castillo K, Noboa L, Argueta-Zamora D, Robayo P, Arizaga E, Caicedo A, and Gavilanes AWD
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- Dopaminergic Neurons pathology, Humans, Mitochondria genetics, Mitochondria pathology, Mitochondrial Dynamics, Reactive Oxygen Species metabolism, Parkinson Disease pathology
- Abstract
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, worldwide. PD neuro-energetically affects the extrapyramidal system, by the progressive loss of striatal dopaminergic neurons in the substantia nigra pars compacta, leading to motor impairment. During the progression of PD, there will be an increase in mitochondrial dysfunction, reactive oxygen species (ROS), stress and accumulation of α-synuclein in neurons. This results in mitochondrial mutations altering their function and fission-fusion mechanisms and central nervous system (CNS) degeneration. Intracellular mitochondrial dysfunction has been studied for a long time in PD due to the decline of mitochondrial dynamics inside neurons. Mitochondrial damage-associated molecular patterns (DAMPs) have been known to contribute to several CNS pathologies especially PD pathogenesis. New and exciting evidence regarding the exchange of mitochondria between healthy to damaged cells in the central nervous system (CNS) and the therapeutic use of the artificial mitochondrial transfer/transplant (AMT) marked a return of this organelle to develop innovative therapeutic procedures for PD. The focus of this review aims to shed light on the role of mitochondria, both intra and extracellularly in PD, and how AMT could be used to generate new potential therapies in the fight against PD. Moreover, we suggest that mitochondrial therapy could work as a preventative measure, motivating the field to move towards this goal., (Copyright © 2022 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
- Published
- 2022
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41. The war against Alzheimer, the mitochondrion strikes back!
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Zambrano K, Barba D, Castillo K, Robayo P, Argueta-Zamora D, Sanon S, Arizaga E, Caicedo A, and Gavilanes AWD
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- Amyloid beta-Peptides metabolism, DNA, Mitochondrial genetics, Humans, Mitochondria metabolism, Reactive Oxygen Species metabolism, Alzheimer Disease genetics
- Abstract
Alzheimer's disease (AD) is a leading neurodegenerative pathology associated with aging worldwide. It is estimated that AD prevalence will increase from 5.8 million people today to 13.8 million by 2050 in the United States alone. AD effects in the brain are well known; however, there is still a lack of knowledge about the cellular mechanisms behind the origin of AD. It is known that AD induces cellular stress affecting the energy metabolism in brain cells. During the pathophysiological advancement of AD, damaged mitochondria enter a vicious cycle, producing reactive oxygen species (ROS), harming mitochondrial DNA and proteins, leading to more ROS and cellular death. Additionally, mitochondria are interconnected with the plaques formed by amyloid-β in AD and have underlying roles in the progression of the disease and severity. For years, the biomedical field struggled to develop new therapeutic options for AD without a significant advancement. However, mitochondria are striking back existing outside cells in a new mechanism of intercellular communication. Extracellular mitochondria are exchanged from healthy to damaged cells to rescue those with a perturbed metabolism in a process that could be applied as a new therapeutic option to repair those brain cells affected by AD. In this review we highlight key aspects of mitochondria's role in CNS' physiology and neurodegenerative disorders, focusing on AD. We also suggest how mitochondria strikes back as a therapeutic target and as a potential agent to be transplanted to repair neurons affected by AD., (Copyright © 2022 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
- Published
- 2022
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42. Availability and Quality of Grief and Bereavement Care in Pediatric Intensive Care Units Around the World, Opportunities for Improvement.
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Grunauer M, Mikesell C, Bustamante G, Aronowitz D, Zambrano K, Icaza-Freire AP, Gavilanes AWD, and Barrera R
- Abstract
Pediatric Intensive Care Units (PICUs) provide multidisciplinary care to critically ill children and their families. Grief is present throughout the trajectory of illness and can peak around the time of death or non-death losses. The objective of this study was to assess how PICUs around the world implement grief and bereavement care (GBC) as part of an integrated model of care. This is a multicenter cross-sectional, prospective survey study. Questionnaires with multiple-choice and open-ended questions focusing on unit infrastructure, personnel, policies, limited patient data, and practices related to GBC for families and health care professionals (HCPs) were completed by on-site researchers, who were HCPs on the direct care of patients. PICU fulfillment of GBC goals was evaluated using a custom scoring based on indicators developed by the Initiative for Pediatric Palliative Care (IPPC). We compared average total and individual items fulfillment scores according to the respective country's World Bank income. Patient characteristics and details of unit infrastructure were also evaluated as potential predictors of total GBC fulfillment scores. Statistical analysis included multilevel generalized linear models (GLM) with a Gaussian distribution adjusted by child age/gender and clustering by center, using high income countries (HICs) as the comparative reference. Additionally, we applied principals of content analysis to analyze and summarize open-ended answers to contextualize qualitative data. The study included 34 PICUs from 18 countries: high-income countries (HICs): 32.4%, upper middle-income countries (UMICs): 44.1%, low middle-income and low-income countries (LMI/LICs): 23.5%. All groups reported some compliance with GBC goals; no group reported perfect fulfillment. We found statistically significant differences in GBC fulfillment scores between HICs and UMICs (specifically, HCP grief support), and between HICs and LMICs (specifically, family grief support and HCP grief support). PICUs world-wide provide some GBC, independent of income, but barriers include lack of financial support, time, and training, overall unit culture, presence of a palliative care consultation service, and varying cultural perceptions of child death. Disparities in GBC for families and HCPs exist and were related to the native countries' income level. Identifying barriers to support families and HCPs, can lead to opportunities of improving GBC in PICUs world-wide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grunauer, Mikesell, Bustamante, Aronowitz, Zambrano, Icaza-Freire, Gavilanes, Barrera and the PICU-MIC Research Group.)
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- 2021
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43. Pain Assessment and Management in Pediatric Intensive Care Units Around the World, an International, Multicenter Study.
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Grunauer M, Mikesell C, Bustamante G, Cobo G, Sánchez S, Román AM, Icaza-Freire AP, Gavilanes AWD, and Wang NE
- Abstract
The adequate assessment and management of pain remains a challenging task in the Pediatric Intensive Care Unit (PICU). Our goal is to describe how pain is assessed and managed in PICUs around the world and to examine how human and material resources impact achievement of this goal. An international multicenter cross-sectional observational study was designed with the participation of 34 PICUs located in urban, suburban, and rural areas of 18 countries. We evaluated how PICUs around the world assessed and managed pain according to the Initiative for Pediatric Palliative Care recommendations, and how human and material resources impacted achievement of this goal. Data was collected for this study from 2016 to 2018 using questionnaires completed by medical doctors and nurses. In this paper, we focus on the indicators related to how pain is managed and assessed. The average achievement of the goal of pain relief across all centers was 72.2% (SD: 21.1). We found a statistically significant trend of more effective pain management scores, routine assessment, proper documentation, and involvement of pain management experts by increasing country income. While there are efforts being made worldwide to improve the knowledge in pain assessment and management, there is a lack of resources to do so appropriately in low-middle-income countries. There is a mismatch between the existing guidelines and policies, which are mainly designed in high income countries, and the resources available in lower resourced environments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grunauer, Mikesell, Bustamante, Cobo, Sánchez, Román, Icaza-Freire, Gavilanes, Wang and The PICU-MIC Research Group.)
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- 2021
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44. Extracellular mitochondria in the cerebrospinal fluid (CSF): Potential types and key roles in central nervous system (CNS) physiology and pathogenesis.
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Caicedo A, Zambrano K, Sanon S, and Gavilanes AWD
- Subjects
- Biomarkers metabolism, Humans, Mitochondria metabolism, Cerebrospinal Fluid metabolism
- Abstract
The cerebrospinal fluid (CSF) has an important role in the transport of nutrients and signaling molecules to the central nervous and immune systems through its circulation along the brain and spinal cord tissues. The mitochondrial activity in the central nervous system (CNS) is essential in processes such as neuroplasticity, neural differentiation and production of neurotransmitters. Interestingly, extracellular and active mitochondria have been detected in the CSF where they act as a biomarker for the outcome of pathologies such as subarachnoid hemorrhage and delayed cerebral ischemia. Additionally, cell-free-circulating mitochondrial DNA (ccf-mtDNA) has been detected in both the CSF of healthy donors and in that of patients with neurodegenerative diseases. Key questions arise as there is still much debate regarding if ccf-mtDNA detected in CSF is associated with a diversity of active or inactive extracellular mitochondria coexisting in distinct pathologies. Additionally, it is of great scientific and medical importance to identify the role of extracellular mitochondria (active and inactive) in the CSF and the difference between them being damage associated molecular patterns (DAMPs) or factors that promote homeostasis. This review analyzes the different types of extracellular mitochondria, methods for their identification and their presence in CSF. Extracellular mitochondria in the CSF could have an important implication in health and disease, which may lead to the development of medical approaches that utilize mitochondria as therapeutic agents., (Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.)
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- 2021
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45. Assessing insulin sensitivity and resistance in syndromes of severe short stature.
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Guevara-Aguirre J, Teran E, Lescano D, Guevara C, Guevara A, Saavedra J, Procel P, Wasserfall C, and Gavilanes AWD
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- Case-Control Studies, Glucose Intolerance etiology, Humans, Prognosis, Syndrome, Dwarfism complications, Glucose Intolerance pathology, Growth Disorders complications, Human Growth Hormone deficiency, Insulin Resistance, Laron Syndrome complications
- Abstract
Individuals affected with two genetic syndromes identified in Ecuador have severe short stature and diminished insulin secretion, along with essentially different GH counterregulatory effects on insulin action, which leads to the appearance of opposing metabolic phenotypes. In the case of Laron syndrome, subjects have enhanced insulin sensitivity and diminished incidence of type 2 diabetes mellitus. In the other clinical entity, individuals have innate insulin resistance, a varying degree of carbohydrate metabolism disturbances, glucose intolerance, and eventually insulin-resistant diabetes mellitus. Since both groups have diminished insulin secretion, the standard homeostatic minimal models for assessment of insulin sensitivity and resistance were used to see if they could properly identify the metabolic status, especially considering that these methodologies are simple and non-invasive procedures., Methods: Fasting insulin concentrations, fasting glucose/fasting insulin ratio and various minimal models were determined in individuals from the two syndromic cohorts, as well as in a control group made of first-degree normal relatives of the insulin-resistant phenotype subjects., Results: The metabolic characteristics of enhanced insulin sensitivity in one of the syndromes and innate insulin resistance in the other could not be properly ascertained by the selected methodology. Furthermore, results were confusing and even discrepant with the clinical findings., Conclusions: The standard homeostatic minimal models could not properly identify or discriminate insulin sensitivity and resistance in subjects with inherently diminished secretion. It is thereby suggested that these models should be used with caution in clinical situations where reduced secretion of the metabolic peptide is found or suspected., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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46. Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage.
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Bustelo M, Barkhuizen M, van den Hove DLA, Steinbusch HWM, Bruno MA, Loidl CF, and Gavilanes AWD
- Abstract
Placental and fetal hypoxia caused by perinatal hypoxic-ischemic events are major causes of stillbirth, neonatal morbidity, and long-term neurological sequelae among surviving neonates. Brain hypoxia and associated pathological processes such as excitotoxicity, apoptosis, necrosis, and inflammation, are associated with lasting disruptions in epigenetic control of gene expression contributing to neurological dysfunction. Recent studies have pointed to DNA (de)methylation, histone modifications, and non-coding RNAs as crucial components of hypoxic-ischemic encephalopathy (HIE). The understanding of epigenetic dysregulation in HIE is essential in the development of new clinical interventions for perinatal HIE. Here, we summarize our current understanding of epigenetic mechanisms underlying the molecular pathology of HI brain damage and its clinical implications in terms of new diagnostic, prognostic, and therapeutic tools., (Copyright © 2020 Bustelo, Barkhuizen, van den Hove, Steinbusch, Bruno, Loidl and Gavilanes.)
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- 2020
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47. Growth hormone receptor deficiency in humans associates to obesity, increased body fat percentage, a healthy brain and a coordinated insulin sensitivity.
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Guevara-Aguirre J, Teran E, Lescano D, Guevara A, Guevara C, Longo V, and Gavilanes AWD
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- Adipose Tissue, Adult, Body Composition, Brain physiology, Carbohydrate Metabolism, Case-Control Studies, Family, Fasting, Female, Functional Neuroimaging, Humans, Laron Syndrome complications, Laron Syndrome diagnostic imaging, Laron Syndrome genetics, Magnetic Resonance Imaging, Male, Middle Aged, Obesity etiology, Postprandial Period, Receptors, Somatotropin genetics, Blood Glucose metabolism, Brain diagnostic imaging, Insulin metabolism, Insulin Resistance, Insulin-Like Growth Factor Binding Protein 1 metabolism, Laron Syndrome metabolism, Obesity metabolism, Triglycerides metabolism
- Abstract
Background: We have shown that subjects with Laron syndrome (LS) due to growth hormone receptor deficiency (GHRD) and their relatives have comparable brain structure and function; moreover, the brain of individuals affected with GHRD appears like those of younger people. While the functionally absent growth hormone receptor and the diminished concentrations of the insulin-like growth factor-I have been associated to these findings, the role of the insulin-glucose axis is emerging as an unavoidable consideration when determining the aetiology of these observations. In consequence, we decided to search for the potential and discrete associations between the neurological findings and several parameters of carbohydrate metabolism that might exist in the subjects affected with GHRD., Subjects and Methods: Individuals affected with GHRD were compared to relative controls. Besides standard measures of anthropometry, body composition and brain characteristics, the elements of the carbohydrate metabolism (CHO), including glucose, insulin, triacylglycerol and the free insulin growth factor binding protein 1 (IGFBP1) concentrations were determined. In addition, the correlations existing between the parameters of CHO and brain characteristics were established., Results: Besides the phenotypical characteristics of GHRD subjects, including those of brain structure and function, enhanced insulin sensitivity, and other minor, we observed that the insulin-regulated IGFBP1 had a consistent negative correlation with the main elements of the carbohydrate metabolism only in the individuals affected with the disease, and not in their relatives., Conclusions: When compared to their relatives, subjects with GHRD who lack the counter-regulatory effects of GH on the insulin axis, despite their increased risk factor profile due to obesity and increased body fat percentage, have a healthy and younger looking brain associated to an enhanced and coordinated insulin sensitivity. Furthermore, it was observed that in the GHRD subjects IGFBP1 negatively correlates, in a constant and systematic manner, with the main elements of the CHO metabolism. These observations suggest a direct relationship between an efficient insulin sensitivity and a healthy brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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48. Frequency of Use, Perceptions and Barriers of Information and Communication Technologies Among Latin American Physicians: An Ecuadorian Cross-Sectional Study.
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Cherrez-Ojeda I, Vanegas E, Felix M, Mata VL, Jiménez FM, Sanchez M, Simancas-Racines D, Cherrez S, Gavilanes AWD, Eschrich J, and Chedraui P
- Abstract
Objective: In recent years, the use of information and communication technologies (ICTs) has increased in various sectors, among which the healthcare service is no exception. However, studies have mostly focused on the use of ICTs among patients with chronic diseases, with few reports on the advantages and barriers of these technologies among physicians, particularly in Latin America. We designed this study to fill in the gap, as an objective assessment of the frequency of use, perceptions, and barriers of ICTs among physicians remains crucial for a successful implementation of these technologies into the mainstream medical practice., Methods: We conducted an anonymous cross-sectional survey-based study in 640 Ecuadorian physicians. The survey used consisted of 13 items and evaluated the frequency of use, perceptions, and barriers of ICTs among physicians. Chi-square tests for goodness of fit and independence were performed, whilst Phi coefficient was interpreted to assess the strength of associations. Fisher exact test was performed when required., Results: Over 90% of physicians reported the use of ICTs to message other colleagues and patients (p=0.000). While 89.5% of physicians used social media to interact with other colleagues, only 58.1% used them to interact with patients (p=0.000). Most participants reported the use of ICTs to search for academic information (p=0.000). Moreover, more than 80.0% agree that ICTs may be used to promote health and medical services, search new job opportunities, get involved in research projects and promote teamwork with colleagues. However, 83.6% of physicians expressed concerns about privacy and patient confidentiality, while 53.8% stated that they lacked the time to use ICTs., Conclusion: High usage of ICTs was found among Ecuadorian physicians. Younger physicians, with less postgraduate years, and non-specialists were more likely to have a positive perception toward ICTs. Privacy and patient confidentiality, followed by time management, were the most reported barriers in our study., Competing Interests: Dr Ivan Cherrez-Ojeda reports grants from Universidad Espiritu Santo, during the conduct of the study. The authors declare no other conflicts of interest related to this work., (© 2020 Cherrez-Ojeda et al.)
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- 2020
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49. Preterm Perinatal Hypoxia-Ischemia Does not Affect Somatosensory Evoked Potentials in Adult Rats.
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Barkhuizen M, Vles JSH, van Mechelen R, Vermeer M, Kramer BW, Chedraui P, Bergs P, van Kranen-Mastenbroek VHJM, and Gavilanes AWD
- Abstract
Somatosensory evoked potentials (SSEPs) are a valuable tool to assess functional integrity of the somatosensory pathways and for the prediction of sensorimotor outcome in perinatal injuries, such as perinatal hypoxia-ischemia (HI). In the present research, we studied the translational potential of SSEPs together with sensory function in the male adult rat with perinatal HI compared to the male healthy adult rat. Both somatosensory response and evoked potential were measured at 10-11 months after global perinatal HI. Clear evoked potentials were obtained, but there were no group differences in the amplitude or latency of the evoked potentials of the preceding sensory response. The bilateral tactile stimulation test was also normal in both groups. This lack of effect may be ascribed to the late age-of-testing and functional recovery of the rats.
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- 2019
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50. Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy.
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Barkhuizen M, van Mechelen R, Vermeer M, Chedraui P, Paes D, van den Hove DLA, Vaes B, Mays RW, Steinbusch HWM, Robertson NJ, Kramer BW, and Gavilanes AWD
- Subjects
- Animals, Animals, Newborn, Disease Models, Animal, Female, Hypoxia drug therapy, Male, Rats, Sprague-Dawley, Asphyxia Neonatorum physiopathology, Brain physiopathology, Hypoxia-Ischemia, Brain physiopathology, Multipotent Stem Cells cytology
- Abstract
There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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