Η συμβολή των μεγάλων μη-κωδικών (long non-coding) RNA στους παγκρεατικούς καρκίνους

Τα τελευταία χρόνια, τα μεγάλα μη-κωδικά RNA (long non-coding RNA, lncRNA), λόγω του ρυθμιστικού τους ρόλου στα μονοπάτια τόσο της καρκινογένεσης όσο και της ογκοκαταστολής, μελετώνται όλο και συχνότερα για το ρόλο τους ως πιθανοί βιοδείκτες διαφόρων νεοπλασιών. Όσον αφορά τον καρκίνο του παγκρέατος η απορύθμιση ορισμένων lncRNA φαίνεται να διαδραματίζει καθοριστικό ρόλο στην καρκινογένεση, στην διηθητική ικανότητα και στο μεταστατικό δυναμικό των καρκινικών κυττάρων. Παρόλα αυτά, υπάρχουν περιορισμένα βιβλιογραφικά δεδομένα που να εξηγούν τη ρυθμιστική αυτή δράση της έκφρασης των lncRNA. Σκοπός της μελέτης μας είναι η αποσαφήνιση της συμβολής των πολυμορφισμών δύο lncRNA και συγκεκριμένα των rs1561927 και rs4759314 των PVT1 και HOTAIR, στην επίπτωση του παγκρεατικού καρκίνου. Για το σκοπό αυτό πραγματοποιήθηκε μια μελέτη ασθενών-μαρτύρων (case control study), στην οποία έγινε ανάλυση των rs1561927 και rs4759314 πολυμορφισμών βασιζόμενη σε δείγμα DNA 111 ασθενών με πορογενές αδενοκαρκίνωμα (ΠΑ), 56 ασθενών με νευροενδοκρινή νεοπλάσματα του παγκρέατος (ΝΝΠ) και 125 υγιών μαρτύρων. Όσον αφορά τον πολυμορφισμό rs1561927 του PVT1 το αλληλόμορφο G βρέθηκε να υπερεκφράζεται σημαντικά τόσο στο ΠΑ όσο και στα ΝΝΠ σε σύγκριση με τους υγιείς μάρτυρες, ενώ το αλληλόμορφο G του πολυμορφισμού rs4759314 του HOTAIR φαίνεται να υπερεκφράζεται μόνο στα ΝΝΠ σε σύγκριση με τους υγιείς μάρτυρες. Επιπλέον, οι γονότυποι AG και GG του PVT1 rs1561927 φαίνεται να σχετίζονται με χειρότερη πρόγνωση στους ασθενείς με ΠΑ. Τα αποτελέσματα της μελέτης μας υποδεικνύουν πως οι πολυμορφισμοί των lncRNA που εξεταστήκαν φαίνεται να εμπλέκονται στην καρκινογένεση τωννεοπλασιών του παγκρέατος, ωστόσο μελέτες μεγαλύτερων πληθυσμών θα χρειαστούν για την επιβεβαίωση των αποτελεσμάτων αυτών.Long non-coding RNA (lncRNA) are emerging as candidate biomarkers of cancer, having regulatory functions in both oncogenic and tumor-suppressive pathways. Concerning pancreatic cancer (PC), deregulation of lncRNA involved in tumor initiation, invasion, and metastasis seem to play a key role. However, data is scarce about regulatory mechanism of lncRNA expression. The aim of our study was to investigate the contribution of two lncRNA polymorphisms (rs1561927 and rs4759313 of PVT1 and HOTAIR, respectively) in PC susceptibility. A case-control study was conducted analysing rs1561927 and rs4759313 polymorphisms using DNA collected in a population-based case-control study of pancreatic cancer [111 Pancreatic Ductal Adenocarcinoma cases (PDAC), 56 Pancreatic Neuroendocrine Tumor (PNET), and 125 healthy controls]. Regarding the PVT1 rs1561927 polymorphism the G allele was significantly overrepresented in both PDAC and PNET patients compared to the controls, while the presence of the HOTAIR rs4759314 G allele was found to be overrepresented in the PNET patients only compared to the controls. The PVT1 rs1561927 AG/GG genotypes were associated with poor overall survival in PDAC patients. Our results suggested that polymorphisms of these two lncRNA polymorphisms implicated in pancreatic carcinogenesis. Further large-scale and functional studies are needed to confirm our results

Highly Sensitive InO x

InOx thin films with a thickness of the order of 100 nm were grown by dc magnetron sputtering on glass, Si and flexible (PET) substrates. The electrical conductivity of InOx thin films exhibited a change of two orders of magnitude during photoreduction with ultraviolet light and subsequent oxidation in ozone concentrations from 2370 to 15 ppb, at room temperature. Optical transparency of over 85% for all substrates was maintained. Film structural and ozone sensing properties were analyzed. Surface morphology investigations carried out by SEM for films on PET substrates showed extended surface cracking for bending angles beyond 40∘. Optimization of growth conditions has led to films with extremely low detection levels for ozone down to 15 ppb at room temperature, demonstrating the wide prospective of utilizing these metal oxides as gas sensors on flexible substrates for a variety of automotive and air-conditioning applications

Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project

Background: Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem.Objectives: The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study.Methods: A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields.Results: During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study.Conclusion: A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting.Keywords: Candidate predictor variables, pediatrics, prediction, post-discharge mortality, sepsi

Global Emergency Medicine: A Review of the Literature From 2013

Objectives The Global Emergency Medicine Literature Review ( GEMLR ) conducts an annual search of peer‐reviewed and grey literature relevant to global emergency medicine ( EM ) to identify, review, and disseminate the most important new research in this field to a worldwide audience of academics and clinical practitioners. Methods This year 8,768 articles written in six languages were identified by our search. These articles were distributed among 22 reviewers for initial screening based on their relevance to the field of global EM . An additional two reviewers searched the grey literature. A total of 434 articles were deemed appropriate by at least one reviewer and approved by an editor for formal scoring of overall quality and importance. Results Of the 434 articles that met our predetermined inclusion criteria, 65% were categorized as emergency care in resource‐limited settings, 18% as EM development, and 17% as disaster and humanitarian response. A total of 24 articles received scores of 18 or higher and were selected for formal summary and critique. Interrater reliability for two reviewers using our scoring system was good, with an intraclass correlation coefficient of 0.63 (95% confidence interval = 0.55 to 0.69). Infectious diseases, trauma, and the diagnosis and treatment of diseases common in resource‐limited settings represented the majority of articles selected for final review. Conclusions In 2013, there were more emergency care in resource‐limited settings articles, while the number of disaster and humanitarian response articles decreased, when compared to the 2012 review. However, the distribution of articles selected for full review did not change significantly. As in prior years, the majority of articles focused on infectious diseases, as well as trauma and injury prevention. Resumen Objetivos El grupo Global Emergency Medicine Literature Review (GEMLR) lleva a cabo una búsqueda anual de revisión por pares y de la literatura gris relevante para la Medicina de Urgencias y Emergencias ( MUE ) Global para identificar, revisar y divulgar las investigaciones recientes más importantes en este campo para la audiencia mundial de profesores universitarios y médicos clínicos. Metodología Se identificaron según nuestra búsqueda 8.768 artículos escritos en seis lenguas en 2013. Estos artículos se distribuyeron entre 22 revisores para un despistaje inicial basado en la relevancia para el área de la MUE Global. Dos revisores adicionales buscaron en la literatura gris. Un total de 434 artículos se consideraron apropiados por al menos un revisor y se aprobaron por un editor mediante una puntación formal de calidad e importancia. Resultados De los 434 artículos que cumplieron los criterios de inclusión predeterminados, un 65% se categorizó como atención urgente en escenarios de recursos limitados, un 18% como desarrollo de la MUE y un 17% como grandes catástrofes y respuesta humanitaria. Un total de 24 artículos recibió puntuaciones de 18 o más y se seleccionaron para el resumen formal y la crítica. La concordancia interobservador para los dos revisores usando nuestro sistema de puntuación fue buena con un coeficiente de correlación intraclase de 0,63 (intervalo de confianza 95% = 0,55 a 0,69). Las enfermedades infecciosas, los traumatismos y el diagnostico y tratamiento de las enfermedades comunes en escenarios de recursos limitados representaron la mayoría de los artículos seleccionados para la revisión final. Conclusiones En 2013, hubo más artículos de atención urgente en escenarios de recursos limitados, mientras que el número de artículos de grandes catástrofes y respuesta humanitaria disminuyó respecto a la revisión de 2012. Sin embargo, la distribución de los artículos seleccionados para la revisión total no cambio significativamente. Como en años anteriores, la mayoría de los artículos se centró en enfermedades infecciosas, así como en la prevención de los traumatismos y las lesiones.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108313/1/acem12414.pd

Individual, maternal and household risk factors for anaemia among young children in sub-Saharan Africa: a cross-sectional study

Objective: Anaemia affects the majority of children in sub-Saharan Africa (SSA). Previous studies of risk factors for anaemia have been limited by sample size, geography and the association of many risk factors with poverty. In order to measure the relative impact of individual, maternal and household risk factors for anaemia in young children, we analysed data from all SSA countries that performed haemoglobin (Hb) testing in the Demographic and Health Surveys. Design and setting This cross-sectional study pooled household-level data from the most recent Demographic and Health Surveys conducted in 27 SSA between 2008 and 2014. Participants: 96 804 children age 6–59 months. Results: The prevalence of childhood anaemia (defined as Hb <11 g/dL) across the region was 59.9%, ranging from 23.7% in Rwanda to 87.9% in Burkina Faso. In multivariable regression models, older age, female sex, greater wealth, fewer household members, greater height-for-age, older maternal age, higher maternal body mass index, current maternal pregnancy and higher maternal Hb, and absence of recent fever were associated with higher Hb in tested children. Demographic, socioeconomic factors, family structure, water/sanitation, growth, maternal health and recent illnesses were significantly associated with the presence of childhood anaemia. These risk factor groups explain a significant fraction of anaemia (ranging from 1.0% to 16.7%) at the population level. Conclusions: The findings from our analysis of risk factors for anaemia in SSA underscore the importance of family and socioeconomic context in childhood anaemia. These data highlight the need for integrated programmes that address the multifactorial nature of childhood anaemia

Individual, maternal and household risk factors for anaemia among young children in sub-Saharan Africa: a cross-sectional study

Objective: Anaemia affects the majority of children in sub-Saharan Africa (SSA). Previous studies of risk factors for anaemia have been limited by sample size, geography and the association of many risk factors with poverty. In order to measure the relative impact of individual, maternal and household risk factors for anaemia in young children, we analysed data from all SSA countries that performed haemoglobin (Hb) testing in the Demographic and Health Surveys. Design and setting This cross-sectional study pooled household-level data from the most recent Demographic and Health Surveys conducted in 27 SSA between 2008 and 2014. Participants: 96 804 children age 6–59 months. Results: The prevalence of childhood anaemia (defined as Hb <11 g/dL) across the region was 59.9%, ranging from 23.7% in Rwanda to 87.9% in Burkina Faso. In multivariable regression models, older age, female sex, greater wealth, fewer household members, greater height-for-age, older maternal age, higher maternal body mass index, current maternal pregnancy and higher maternal Hb, and absence of recent fever were associated with higher Hb in tested children. Demographic, socioeconomic factors, family structure, water/sanitation, growth, maternal health and recent illnesses were significantly associated with the presence of childhood anaemia. These risk factor groups explain a significant fraction of anaemia (ranging from 1.0% to 16.7%) at the population level. Conclusions: The findings from our analysis of risk factors for anaemia in SSA underscore the importance of family and socioeconomic context in childhood anaemia. These data highlight the need for integrated programmes that address the multifactorial nature of childhood anaemia

Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project.

Background: Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem. Objectives: The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study. Methods: A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields. Results: During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study. Conclusion: A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting

Protecting children in low-income and middle-income countries from COVID-19

CITATION: Ahmed, S. et al. 2020. Protecting children in low-income and middle-income countries from COVID-19. BMJ Global Health, 5:e002844. doi:10.1136/bmjgh-2020-002844.The original publication is available at https://gh.bmj.comA saving grace of the COVID-19 pandemic in high-income and upper middle-income countries has been the relative sparing of children. As the disease spreads across low-income and middle-income countries (LMICs), long-standing system vulnerabilities may tragically manifest, and we worry that children will be increasingly impacted, both directly and indirectly. Drawing on our shared child pneumonia experience globally, we highlight these potential impacts on children in LMICs and propose actions for a collective response.https://gh.bmj.com/content/5/5/e002844.abstractPublisher's versio

The epidemiological landscape of anemia in women of reproductive age in sub-Saharan Africa

The role of geographical disparities of health-related risk factors with anemia are poorly documented for women of reproductive age in sub-Saharan Africa (SSA). We aimed to determine the contribution of potential factors and to identify areas at higher risk of anemia for women in reproductive age in SSA. Our study population comprised 27 nationally representative samples of women of reproductive age (15–49) who were enrolled in the Demographic and Health Surveys and conducted between 2010 and 2019 in SSA. Overall, we found a positive association between being anemic and the ecological exposure to malaria incidence [adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) 1.02–1.02], and HIV prevalence (AOR = 1.01, CI 1.01–1.02). Women currently pregnant or under deworming medication for the last birth had 31% (AOR = 1.31, CI 1.24–1.39) and 5% (AOR = 1.05, CI 1.01–1.10) higher odds of having anemia, respectively. Similarly, women age 25–34 years old with low education, low income and living in urban settings had higher odds of having anemia. In addition, underweight women had 23% higher odds of suffering anemia (AOR = 1.23, CI 1.15–1.31). Females with low levels of education and wealth index were consistently associated with anemia across SSA. Spatial distribution shows increased risk of anemia in Central and Western Africa. Knowledge about the contribution of known major drivers and the spatial distribution of anemia risk can mitigate operational constraints and help to design geographically targeted intervention programs in SSA