ABSTRACT
PURPOSE: The aim of this study is to compare optical quality results obtained in laboratory analysis (in vitro) versus clinical data (in vivo). METHODS: The optical quality of ISOPure intraocular lens was assessed both in vitro and in vivo using the modulation transfer function (MTF) for 3.0 and 4.5 mm pupil diameters. In vitro measurements were obtained using deflectometer NIMO TRF1504, while in vivo measurements were taken with OPD-Scan III in a set of patients implanted with this lens. Ray tracing techniques were used to determine the MTF and area under MTF curve (MTFa) from the measured wavefront for the isolated lens and for the whole eye. RESULTS: The MTF of the isolated lens obtained under both in vitro and in vivo conditions showed comparable results for both pupil sizes. However, differences were found when comparing the MTF of the whole eye with the lens implanted versus the MTF measured in vitro for 4.5 mm pupil size. Also, the MTFa defocus curve was compared with the defocus curve measured in vivo. CONCLUSION: The defocus curve from the in vivo study aligns closely with the MTFa of the in vitro model, with a useful defocus range of 0.40D. Thus, it is possible to anticipate the visual results of the implanted isofocal lens by using measurements on an optical bench and conducting optical simulations.
ABSTRACT
PURPOSE: This study is to evaluate the optical characteristics of a non-diffractive wavefront-shaping intraocular lens which incorporates surface refractive modifications for shaping the wavefront in order to achieve extended depth of focus (EDoF) and to assess whether the nominal power of this IOL influences the attainable add power. METHODS: A commercially available optical bench NIMO TR1504 device (LAMBDA-X, Nivelles, Belgium) was employed to obtain full optical characterization of three non-diffractive EDoF intraocular lenses with + 10 D, + 20 D, and + 30 D powers. After NIMO measurements, data were computed using a custom-made MATLAB program (Mathworks, Inc., Natick, MA, USA) to evaluate the optical quality functions, such as the point spread function (PSF), wavefront profiles, and modulation transfer function (MTF) for two pupil sizes: 3 mm and 4.0 mm. RESULTS: The non-diffractive EDoF intraocular lens showed a central serrated power profile behavior with additions of + 2.00 to + 2.50 D over the nominal power. Higher order aberrations were found to be driven mainly by the spherical aberration, with almost null comatic influence. Optical quality metrics showed good values, better for a 3 mm pupil compared to a 4.5 mm one, as expected. The three IOL powers tested showed a very similar behavior in terms of power and aberrometric profiles, with minimal to null differences related to the nominal power. CONCLUSION: The non-diffractive wavefront-shaping EDoF intraocular lens achieves a near addition up to + 2.50 D aiming for an extended range of vision, almost independently of the base power.
Subject(s)
Depth Perception , Lenses, Intraocular , Optics and Photonics , Prosthesis Design , Refraction, Ocular , Visual Acuity , Humans , Refraction, Ocular/physiology , Depth Perception/physiology , Visual Acuity/physiology , Corneal Wavefront Aberration/physiopathology , Corneal Wavefront Aberration/diagnosisABSTRACT
INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.
Subject(s)
Adrenergic beta-Antagonists , Angiotensin Receptor Antagonists , Heart Failure , Mineralocorticoid Receptor Antagonists , Renal Insufficiency, Chronic , Sodium-Glucose Transporter 2 Inhibitors , Stroke Volume , Humans , Heart Failure/complications , Heart Failure/drug therapy , Heart Failure/physiopathology , Retrospective Studies , Male , Female , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Aged , Cross-Sectional Studies , Mineralocorticoid Receptor Antagonists/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume/physiology , Middle Aged , Spain/epidemiology , Guideline Adherence , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Aged, 80 and overABSTRACT
Introducción: Este estudio trata de valorar la repercusión de la pandemia sobre la incidencia y la evolución clínica de la infección periamigdalina (IPA).Material y métodosRevisamos en un seguimiento longitudinal y descriptivo retrospectivo las circunstancias de los pacientes atendidos durante 5 años, de 2017 a 2021, en dos hospitales, uno comarcal y otro terciario. Se registraron variables relacionadas con la patología de base, antecedentes de amigdalitis, tiempo de evolución, visitas previas en Atención Primaria, hallazgos en el diagnóstico, relación absceso/flemón y días de estancia hospitalaria.ResultadosDe 2017 a 2019 la incidencia de la enfermedad osciló entre 14 y 16 casos/100.000 habitantes-año, pero en 2020 se redujo a 9,3, un 43% menos. Los pacientes con IPA que consultaron en pandemia generaron pocas visitas previas en servicios de Atención Primaria, presentaron mayor severidad de los síntomas y mayor demora en el diagnóstico. Además, hubo más abscesos que flemones y la necesidad de ingreso hospitalario superior a 24h fue del 66%. Apenas hubo causalidad con amigdalitis agudas, aunque el 66% de los pacientes padecía amigdalitis de repetición, y el 71% patología concomitante. Todos estos hallazgos mostraron diferencias estadísticamente significativas respecto a los casos prepandemia.ConclusionesLa protección de la transmisión aérea, el distanciamiento social y el confinamiento adoptados en nuestro país son medidas que han podido modificar la evolución de la IPA, con una incidencia muy inferior, un período de recuperación mayor y mínima relación con amigdalitis aguda. (AU)
Introduction: This study assessed if the healthcare system overload and the organizational changes made in response to COVID-19 may be having an impact on clinical and epidemiological characteristics of the peritonsillar infection (PTI).Materials and methodsIn a retrospective longitudinal and descriptive follow-up, we reviewed the circumstances of the patients attended during 5 years, from 2017 to 2021, in two hospitals, one regional and other tertiary. Variables related to underlying pathology, history of tonsillitis, time of evolution, previous visits to Primary Care, diagnostic findings, abscess/phlegmon ratio, and length of hospital stay were recorded.ResultsFrom 2017 to 2019, the incidence of the disease ranged between 14 and 16 cases/100,000 inhabitants-year, and decreased to 9.3 in 2020, a 43% less. Patients with PTI consulting in pandemic time were visited much less often in Primary Care services. They showed a greater severity of symptoms and the period of time between their appearance and diagnosis was longer. Additionally, there were more abscesses and the need for hospital admission greater than 24h was 66%. There was hardly a causal relationship with acute tonsillitis, although 66% of the patients evidenced history of recurrent tonsillitis, and 71% concomitant pathology. All these findings showed statistically significant differences with the pre-pandemic cases.ConclusionsThe protection of airborne transmission, the social distancing and the lockdown adopted in our country are measures that seem having been able to modify the evolution of PTI, with a much lower incidence, a longer recovery period and a minimal relationship with acute tonsillitis. (AU)
Subject(s)
Humans , Primary Health Care , Otolaryngology , Epidemiology , Severe acute respiratory syndrome-related coronavirus , Coronavirus Infections/epidemiology , PandemicsABSTRACT
INTRODUCTION: This study assessed if the healthcare system overload and the organizational changes made in response to COVID-19 may be having an impact on clinical and epidemiological characteristics of the peritonsillar infection (PTI). MATERIALS AND METHODS: In a retrospective longitudinal and descriptive follow-up, we reviewed the circumstances of the patients attended during 5 years, from 2017 to 2021, in two hospitals, one regional and other tertiary. Variables related to underlying pathology, history of tonsillitis, time of evolution, previous visits to Primary Care, diagnostic findings, abscess/phlegmon ratio, and length of hospital stay were recorded. RESULTS: From 2017 to 2019, the incidence of the disease ranged between 14 and 16 cases/100,000 inhabitants-year, and decreased to 9.3 in 2020, a 43% less. Patients with PTI consulting in pandemic time were visited much less often in Primary Care services. They showed a greater severity of symptoms and the period of time between their appearance and diagnosis was longer. Additionally, there were more abscesses and the need for hospital admission greater than 24h was 66%. There was hardly a causal relationship with acute tonsillitis, although 66% of the patients evidenced history of recurrent tonsillitis, and 71% concomitant pathology. All these findings showed statistically significant differences with the pre-pandemic cases. CONCLUSIONS: The protection of airborne transmission, the social distancing and the lockdown adopted in our country are measures that seem having been able to modify the evolution of PTI, with a much lower incidence, a longer recovery period and a minimal relationship with acute tonsillitis.
Subject(s)
COVID-19 , Peritonsillar Abscess , Tonsillectomy , Tonsillitis , Humans , Pandemics/prevention & control , Retrospective Studies , Tonsillectomy/adverse effects , COVID-19/complications , COVID-19/epidemiology , Communicable Disease Control , Peritonsillar Abscess/epidemiology , Tonsillitis/epidemiology , Tonsillitis/surgery , Delivery of Health CareABSTRACT
Introduction: This study assessed if the healthcare system overload and the organizational changes made in response to COVID-19 may be having an impact on clinical and epidemiological characteristics of the peritonsillar infection (PTI). Materials and methods: In a retrospective longitudinal and descriptive follow-up, we reviewed the circumstances of the patients attended during 5 years, from 2017 to 2021, in two hospitals, one regional and other tertiary. Variables related to underlying pathology, history of tonsillitis, time of evolution, previous visits to Primary Care, diagnostic findings, abscess/phlegmon ratio, and length of hospital stay were recorded. Results: From 2017 to 2019, the incidence of the disease ranged between 14 and 16 cases/100,000 inhabitants-year, and decreased to 9.3 in 2020, a 43% less. Patients with PTI consulting in pandemic time were visited much less often in Primary Care services. They showed a greater severity of symptoms and the period of time between their appearance and diagnosis was longer. Additionally, there were more abscesses and the need for hospital admission greater than 24 h was 66%. There was hardly a causal relationship with acute tonsillitis, although 66% of the patients evidenced history of recurrent tonsillitis, and 71% concomitant pathology. All these findings showed statistically significant differences with the pre-pandemic cases. Conclusions: The protection of airborne transmission, the social distancing and the lockdown adopted in our country are measures that seem having been able to modify the evolution of PTI, with a much lower incidence, a longer recovery period and a minimal relationship with acute tonsillitis.
Subject(s)
Stomach Neoplasms , Gastrectomy , Humans , Lymph Node Excision , Spleen/surgery , Stomach Neoplasms/surgeryABSTRACT
Introducción: Las enfermedades crónicas implican un reto sanitario e intersectorial. Por ello, los prestadores requieren adquirir competencias específicas según estándares nacionales e internacionales para implantar una atención primaria de salud que provea acceso y cobertura universal. Objetivo: Reflexionar sobre elementos relevantes vinculados a las competencias de los proveedores de salud para la atención de personas con condiciones crónicas, en el contexto de la atención primaria de salud. Métodos: Se discuten estrategias, la implementación del Modelo de Cuidados Crónicos y la adquisición de competencias, analizando aspectos de la formación profesional, el aseguramiento de la educación continua y la disposición de los proveedores para estar a la vanguardia de los cuidados. Conclusiones: Para proveer una atención integral a personas con enfermedades crónicas es necesario el fortalecimiento del capital humano y la instalación de relaciones coproductivas entre el equipo multidisciplinario. Además, es fundamental que los equipos conozcan e incorporen estrategias con demostración de eficacia a nivel internacional, entre ellos se encuentra el Modelo de Cuidados Crónicos, cuya implementación ha sido lenta y con desarrollo parcial(AU)
Introduction: Chronic diseases represent a health and intersectoral challenge. Therefore, providers need to acquire specific competences according to national and international standards, in order to implement primary healthcare providing universal access and coverage. Objective: To reflect on the relevant elements related to the competences of healthcare providers for the care of people with chronic conditions in the context of primary healthcare. Methods: Strategies are discussed, together with the implementation of the chronic care model and the acquisition of competences, analyzing aspects of professional training, the assurance of continuing education and the willingness of providers to be at the forefront of care. Conclusions: In order to provide comprehensive care to people with chronic diseases, it is necessary to strengthen human capital and create coproductive relationships among the multidisciplinary team. In addition, it is essential that the teams be aware of and incorporate strategies that have been shown to be effective at the international level, including the chronic care model, whose implementation has been slow and only partially developed(AU)
Subject(s)
Humans , Primary Health Care , Chronic Disease , Health Personnel/education , Competency-Based Education , Education, Continuing , Health Workforce , ChileABSTRACT
RESUMEN Objetivo: Evaluar las habilidades de comunicación durante la entrevista clínica, en el contexto de la Simulación Clínica (SC) con Paciente Simulado (PS) y Role Playing (RP). Material y Método: Investigación con aplicación del método mixto de tipo secuencial explicativo, en el contexto de una asignatura electiva de innovación en el Departamento de Enfermería de la Universidad de Atacama. La primera etapa fue cuantitativa de tipo correlacional, aplicando una versión abreviada de la Master Interview Rating Scale (MIRS) a diez estudiantes de enfermería. Cada uno realizó tres entrevistas clínicas con metodología de SC con PS, y tres con RP. Para la hipótesis correlacional se calculó t student. La segunda etapa fue cualitativa de tipo fenomenológica, alcanzando la saturación con dos grupos focales. Los datos se analizaron línea por línea, con categorización emergente, y triangulación de investigadores y datos. Resultados: Se obtuvo un t student de 12,161, aceptando la hipótesis: "En la SC con PS los estudiantes demuestran una mejor aplicación de las habilidades de comunicación". Se identificaron 23 códigos y tres categorías centrales que describen la importancia de la SC en la aplicación de las habilidades de comunicación. Conclusiones: La aplicación de habilidades de comunicación durante la entrevista clínica fue evaluada positivamente desde la dimensión cuantitativa y cualitativa, obteniendo puntuaciones que demuestran un alto porcentaje de cumplimiento y una evaluación perceptiva positiva entre los participantes.
ABSTRACT Objective: To evaluate communication skills during the clinical interview, in the context of Clinical Simulation (CS) with Simulated Patient (SP) and Role Playing (RP). Material and Method: Application research using sequential explanatory mixed method in the context of an optional innovation course at the Department of Nursing of the University of Atacama (Chile). The first stage was quantitative correlational, applying an abbreviated version of the Master Interview Rating Scale (MIRS) to ten nursing students. Each one conducted three clinical interviews using CS methodology with SP, and three with RP. For the correlational hypothesis, Student's t was calculated. The second stage was qualitative phenomenological, reaching saturation with two focus groups. The data was analyzed line by line, with emergent categorization, and with triangulation of researchers and data. Results: A Student's t of 12,161 was obtained, accepting the hypothesis: "In the CS with SP students demonstrate a better application of communication skills". 23 codes and 3 central categories that describe the importance of the CS in the application of communication skills were identified. Conclusions: The application of communication skills during the clinical interview was positively evaluated from the quantitative and qualitative dimensions; obtaining scores that show a high percentage of compliance, and a positive perceptual evaluation among participants.
RESUMO Objetivo: Avaliar as habilidades de comunicação durante a entrevista clínica, no contexto de Simulação Clínica (SC) com Paciente Simulado (PS) e Role Playing (RP). Material e Método: Pesquisa com aplicação do método sequencial misto, no contexto de uma disciplina de inovação eletiva do Departamento de Enfermagem da Universidade de Atacama (Chile). A primeira etapa foi quantitativa do tipo correlacional, aplicando-se uma versão abreviada da Master Interview Rating Scale (MIRS) a dez estudantes de enfermagem. Cada um realizou três entrevistas clínicas com a metodologia SC com PS e três com RP. Para a hipótese correlacional, foi calculado o t de Student. A segunda etapa foi qualitativa de tipo fenomenológico, alcançando a saturação com dois grupos focais. Os dados foram analisados linha a linha, com categorização emergente, e com triangulação de pesquisadores e dados. Resultados: Obteve-se um t de Student de 12.161, aceitando a hipótese: "Em SC com PS, os alunos demonstram uma melhor aplicação das habilidades de comunicação". Foram identificados 23 códigos e três categorias centrais que descrevem a importância da SC na aplicação das habilidades de comunicação. Conclusões: A aplicação das habilidades de comunicação durante a entrevista clínica foi avaliada positivamente na dimensão quantitativa e qualitativa; obtenção de escores que mostram alto percentual de adesão e avaliação perceptual positiva entre os participantes.
ABSTRACT
AIM: The aim of the study was to evaluate urgent care practice with regard to anorectal abscesses (AA) in a tertiary-level referral hospital. MATERIALS AND METHODS: this was retrospective and unicentric study. Patients who underwent surgery for AA between 2016 and 2017 were included in the study. Demographic variables were analyzed as well as the treatment performed, the need for hospitalization, use of antibiotics, and referral to the coloproctology outpatient department (COD). The recurrence risk factors were also evaluated. RESULTS: A total of 220 evaluations under anesthesia were performed, corresponding to 190 patients, 129 males (mean age 46 ± 14.9 years). The most frequent treatment in the emergency department (ED) was simple drainage (75.8%). Antibiotic therapy was prescribed in 62.9% of the cases. A total of 41.1% of the patients were referred to a specialized COD. The only risk factor associated with recurrence was the presence of an associated anal fistula. CONCLUSIONS: Anorectal abscesses are very frequent in the ED. There is great clinical variability regarding the taking of cultures, prescription of antibiotics, and referral criteria to a specialized coloproctology outpatient department, without clear impact of any of them on the recurrence of the abscess.
OBJETIVO: Evaluar el manejo de los abscesos perianales por parte del servicio de cirugía de urgencias. MÉTODO: Estudio unicéntrico retrospectivo. Se incluyeron pacientes que requirieron manejo quirúrgico de abscesos perianales de 2016 a 2017. Se analizaron variables demográficas, tratamientos realizados, necesidad de ingreso hospitalario, uso de antibióticos y necesidad de derivación a la consulta externa de coloproctología. Así mismo, se evaluaron los factores relacionados con la recurrencia del absceso. RESULTADOS: Durante el periodo de estudio se realizaron 220 exploraciones, correspondientes a 190 pacientes (129 hombres) con una edad media de 46 ± 14.9 años. El tratamiento quirúrgico más frecuentemente realizado fue el drenaje simple (75.8%). Se prescribieron antibióticos en el 62.9% de los casos. El 41.1% de los pacientes fueron remitidos a consulta externa de coloproctología. El único factor de riesgo asociado a la recurrencia fue la presencia de una fístula perianal asociada. CONCLUSIONES: Los abscesos perianales son frecuentes en los servicios de urgencias. Hay una gran variabilidad clínica en su manejo, sobre todo en lo relativo a la realización de cultivos, la prescripción de antibióticos y la derivación a unidades de coloproctología especializadas, sin que ninguna de estas medidas tenga un claro impacto en la recurrencia.
Subject(s)
Anus Diseases , Rectal Fistula , Abscess/drug therapy , Abscess/surgery , Ambulatory Care , Anus Diseases/drug therapy , Anus Diseases/surgery , Drainage , Humans , Male , Middle Aged , Retrospective StudiesSubject(s)
Colonic Neoplasms/complications , Intestinal Obstruction/etiology , Intussusception/etiology , Lipoma/complications , Abdominal Pain/etiology , Colonic Neoplasms/diagnostic imaging , Constipation/etiology , Humans , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/surgery , Intussusception/diagnostic imaging , Intussusception/surgery , Laparoscopy , Lipoma/diagnostic imaging , Male , Middle AgedABSTRACT
RESUMEN Objetivo: describir las características de la práctica de enfermería en el cuidado de personas con diabetes mellitus tipo 2 en la atención primaria de salud, según la Teoría de la Atención Burocrática. Material y método: investigación cualitativa que exploró la práctica de enfermería en el cuidado del paciente con diabetes mellitus tipo 2, por medio de la observación no participante; se realizó durante tres semanas en dos centros de salud familiar en la región de Atacama, Chile; se utilizaron notas de campo y se analizó la información por medio de comparación constante, según el referente filosófico seleccionado. Resultados: el cuidado de enfermería en personas con diabetes mellitus tipo 2 en los centros de salud familiar se encuentra vinculado a todos los factores señalados en la Teoría de la Atención Burocrática, es decir, factores educativos, físicos, socioculturales, legales, tecnológicos, económicos y políticos. Conclusiones: por medio de la Teoría de la Atención Burocrática es posible describir la práctica del cuidado de enfermería en personas con diabetes mellitus tipo 2. Enfermería debe considerar los factores propios a la burocracia de toda organización, especialmente al momento de gestionar el cuidado en este tipo de pacientes.
ABSTRACT Objective: describe the characteristics of nursing practice regarding the care of persons with diabetes mellitus type 2 within the scope of primary health care, according to the Theory of Bureaucratic Caring. Materials and method: A qualitative study was done to explore nursing practice with respect to the care of patients with diabetes mellitus type 2, through non-participant observation over a period of three weeks at two family healthcare centers in the Atacama region of Chile. Field notes were used and the information was analyzed through constant comparison, according to the selected philosophical referent. Results: Nursing care provided at family healthcare centers to persons with diabetes mellitus type 2 is linked to all the factors indicated in the Theory of Bureaucratic Caring; that is, educational, physical, sociocultural, legal, technological, economic and political factors. Conclusions: The Theory of Bureaucratic Caring can be used to describe nursing practice in the care of persons with diabetes mellitus type 2. Nursing should consider the factors inherent in the bureaucracy of any organization, especially when managing care for patients of this type.
RESUMO Objetivo: descrever as características da prática de enfermagem no cuidado de pessoas com Diabetes Mellitus tipo 2 na atenção primária de saúde, segundo a Teoria da Atenção Burocrática. Material e método: pesquisa qualitativa que explorou a prática de enfermagem no cuidado do paciente com Diabetes Mellitus tipo 2 por meio da observação não participante; realizou-se durante três semanas em duas unidades de saúde da família na região de Atacama, Chile; utilizaram-se anotações de campo e analisou-se a informação pela comparação constante, conforme o referencial filosófico selecionado. Resultados: o cuidado de enfermagem em pessoas com Diabetes Mellitus tipo 2 nas unidades de saúde da família encontra-se vinculado com todos os fatores apontados na Teoria da Atenção Burocrática, isto é, fatores educativos, físicos, socioculturais, legais, tecnológicos, econômicos e políticos. Conclusões: por meio da Teoria da Atenção Burocrática, é possível descrever a prática do cuidado de enfermagem em pessoas com Diabetes Mellitus tipo 2. A enfermagem deve considerar os fatores próprios à burocracia de toda organização, em especial, no momento de administrar o cuidado nesse tipo de paciente.
Subject(s)
Humans , Primary Health Care , Nursing , Diabetes Mellitus, Type 2 , Philosophy, Nursing , ObservationSubject(s)
Humans , Public Health , Quality Indicators, Health Care , Nursing Care , Public Policy , Health EquityABSTRACT
BACKGROUND: Sustained and dysfunctional macrophage activation promotes inflammatory cardiometabolic disorders, but the role of long intergenic noncoding RNA (lincRNA) in human macrophage activation and cardiometabolic disorders is poorly defined. Through transcriptomics, bioinformatics, and selective functional studies, we sought to elucidate the lincRNA landscape of human macrophages. METHODS AND RESULTS: We used deep RNA sequencing to assemble the lincRNA transcriptome of human monocyte-derived macrophages at rest and following stimulation with lipopolysaccharide and IFN-γ (interferon γ) for M1 activation and IL-4 (interleukin 4) for M2 activation. Through de novo assembly, we identified 2766 macrophage lincRNAs, including 861 that were previously unannotated. The majority (≈85%) was nonsyntenic or was syntenic but not annotated as expressed in mouse. Many macrophage lincRNAs demonstrated tissue-enriched transcription patterns (21.5%) and enhancer-like chromatin signatures (60.9%). Macrophage activation, particularly to the M1 phenotype, markedly altered the lincRNA expression profiles, revealing 96 lincRNAs differentially expressed, suggesting potential roles in regulating macrophage inflammatory functions. A subset of lincRNAs overlapped genomewide association study loci for cardiometabolic disorders. MacORIS (macrophage-enriched obesity-associated lincRNA serving as a repressor of IFN-γ signaling), a macrophage-enriched lincRNA not expressed in mouse macrophages, harbors variants associated with central obesity. Knockdown of MacORIS, which is located in the cytoplasm, enhanced IFN-γ-induced JAK2 (Janus kinase 2) and STAT1 (signal transducer and activator of transcription 1) phosphorylation in THP-1 macrophages, suggesting a potential role as a repressor of IFN-γ signaling. Induced pluripotent stem cell-derived macrophages recapitulated the lincRNA transcriptome of human monocyte-derived macrophages and provided a high-fidelity model with which to study lincRNAs in human macrophage biology, particularly those not conserved in mouse. CONCLUSIONS: High-resolution transcriptomics identified lincRNAs that form part of the coordinated response during macrophage activation, including specific macrophage lincRNAs associated with human cardiometabolic disorders that modulate macrophage inflammatory functions.
Subject(s)
Cardiovascular Diseases/genetics , Gene Expression Regulation , Macrophage Activation/genetics , Macrophages/metabolism , Metabolic Syndrome/genetics , RNA, Long Noncoding/genetics , RNA/genetics , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Cells, Cultured , Genome-Wide Association Study , High-Throughput Nucleotide Sequencing , Humans , Macrophages/pathology , Metabolic Syndrome/metabolism , Metabolic Syndrome/pathology , RNA, Long Noncoding/biosynthesis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Emerging data suggest that the genetic regulation of the biological response to inflammatory stress may be fundamentally different to the genetic underpinning of the homeostatic control (resting state) of the same biological measures. In this paper, we interrogate this hypothesis using a single-SNP score test and a novel class-level testing strategy to characterize protein-coding gene and regulatory element-level associations with longitudinal biomarker trajectories in response to stimulus. Using the proposed class-level association score statistic for longitudinal data, which accounts for correlations induced by linkage disequilibrium, the genetic underpinnings of evoked dynamic changes in repeatedly measured biomarkers are investigated. The proposed method is applied to data on two biomarkers arising from the Genetics of Evoked Responses to Niacin and Endotoxemia study, a National Institutes of Health-sponsored investigation of the genomics of inflammatory and metabolic responses during low-grade endotoxemia. Our results suggest that the genetic basis of evoked inflammatory response is different than the genetic contributors to resting state, and several potentially novel loci are identified. A simulation study demonstrates appropriate control of type-1 error rates, relative computational efficiency, and power. Copyright © 2017 John Wiley & Sons, Ltd.
Subject(s)
Biomarkers , Longitudinal Studies , Models, Statistical , Polymorphism, Single Nucleotide , Biometry/methods , Computer Simulation , Endotoxemia , Humans , Linear Models , Linkage Disequilibrium , Niacin , Open Reading Frames/geneticsABSTRACT
Objective: determine the prevalence of Effective Universal Coverage of Diabetes Mellitus Type 2 in Chile and its relation with the variables: Health Care Coverage of Diabetes Mellitus Type 2; Average of diabetics with metabolic control in 2011-2013; Mortality Rate for Diabetes Mellitus; and Percentage of nurses participating in the Cardiovascular Health Program. Method: cross-sectional descriptive study with ecological components that uses documentary sources of the Ministry of Health. It was established that there is correlation between the Universal Effective Coverage of Diabetes Mellitus Type 2 and the independent variables; it was applied the Pearson Coefficient, being significant at the 0.05 level. Results: in Chile Universal Health Care Coverage of Diabetes Mellitus Type 2 (HbA1c<7% estimated population) is less than 20%; this is related with Mortality Rate for Diabetes Mellitus and Percentage of nurses participating in the Cardiovascular Health Program, being significant at the 0.01 level. Conclusion: effective prevalence of Universal Health Coverage of Diabetes Mellitus Type 2 is low, even though some regions stand out in this research and in the metabolic control of patients who participate in health control program; its relation with percentage of nurses participating in the Cardiovascular Health Program represents a challenge and an opportunity for the health system.
Subject(s)
Diabetes Mellitus, Type 2 , Universal Health Insurance/statistics & numerical data , Chile , Cross-Sectional Studies , Diabetes Mellitus, Type 2/therapy , HumansABSTRACT
Understanding the complex interplay among protein coding genes and regulatory elements requires rigorous interrogation with analytic tools designed for discerning the relative contributions of overlapping genomic regions. To this aim, we offer a novel application of Bayesian variable selection (BVS) for classifying genomic class level associations using existing large meta-analysis summary level resources. This approach is applied using the expectation maximization variable selection (EMVS) algorithm to typed and imputed SNPs across 502 protein coding genes (PCGs) and 220 long intergenic non-coding RNAs (lncRNAs) that overlap 45 known loci for coronary artery disease (CAD) using publicly available Global Lipids Gentics Consortium (GLGC) (Teslovich et al., 2010; Willer et al., 2013) meta-analysis summary statistics for low-density lipoprotein cholesterol (LDL-C). The analysis reveals 33 PCGs and three lncRNAs across 11 loci with >50% posterior probabilities for inclusion in an additive model of association. The findings are consistent with previous reports, while providing some new insight into the architecture of LDL-cholesterol to be investigated further. As genomic taxonomies continue to evolve, additional classes such as enhancer elements and splicing regions, can easily be layered into the proposed analysis framework. Moreover, application of this approach to alternative publicly available meta-analysis resources, or more generally as a post-analytic strategy to further interrogate regions that are identified through single point analysis, is straightforward. All coding examples are implemented in R version 3.2.1 and provided as supplemental material.