Short- and mid-term morbidity and primary-care burden due to infant respiratory syncytial virus infection: A Spanish 6-year population-based longitudinal study.

BACKGROUND: The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach. METHODS: Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period. RESULTS: The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection. CONCLUSIONS: Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs.

COVID-19 vaccine effectiveness in children by age groups. A population-based study in Galicia, Spain.

BACKGROUND: Studies on vaccine effectiveness (VE) against COVID-19 in the pediatric population are outgoing. We aimed to quantify VE against SARS-CoV-2 in two pediatric age groups, 5-11 and 12-17-year-old, while considering vaccine type, SARS-CoV-2 variant, and duration of protection. METHODS: A population-based test-negative control study was undertaken in Galicia, Spain. Children 5-11-year-old received the Comirnaty® (Pfizer, US) vaccine, while those aged 12-17-year-old received the Comirnaty® (Pfizer, US) or SpikeVax® (ModernaTX, Inc) vaccine. Participants were categorized into unvaccinated (0 doses or one dose with <14 days since vaccination), partially vaccinated (only one dose with ≥14 days, or two doses with <14 days after the second dose administration), and fully vaccinated (two doses with ≥14 days after the second injection). Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were estimated using multiple logistic regression models. VE was calculated as (1-OR) * 100. Stratified and sensitivity analyses were performed. RESULTS: In the fully vaccinated 5-11-year-old children, VE against the Omicron variant was 44.1% (95% CI: 38.2%-49.4%). In the fully vaccinated 12-17-year-old individuals, VE was 83.4% (95% CI: 81.2%-85.3%) against Delta and 74.8% (95% CI: 58.5%-84.9%) against Omicron. Comirnaty® and SpikeVax® vaccines showed a similar magnitude of VE against Delta [Comirnaty® VE: 81.9% (95% CI: 79.3%-84.1%) and SpikeVax® VE: 85.3% (95% CI: 81.9%-88.1%)]. Comirnaty® (Pfizer, US; VE: 79.7%; 95% CI: 50.7%-92.4%) showed a slightly higher magnitude of protection against Omicron than SpikeVax® (ModernaTX, Inc), yet with an overlapping CI (VE: 74.3%; 95% CI: 56.6%-84.9%). VE was maintained in all age subgroups in both pediatric populations, but it declined over time. CONCLUSIONS: In Galicia, mRNA VE was moderate against SARS-CoV-2 infections in the 5-11-year-old populations, but high in older children. VE declined over time, suggesting a potential need for booster dose schedules.

Suspected case of monkeypox reinfection versus reactivation in a immunocompetent patient, Barcelona, 2022.

Vaccines against smallpox are known to have cross-protective activity against monkeypox, and smallpox and monkeypox infections are believed to generate permanent immunity. Nevertheless, there are scarce data about the possibility of reinfection or reactivation. Recently, a case of apparent monkeypox reinfection has been reported. We present a suspected case of second episode of monkeypox in a healthy and previously vaccinated man, with a confirmed primary monkeypox infection occurring three months before the second confirmed presentation.

Effectiveness of COVID-19 vaccine booster in the general population and in subjects with comorbidities. A population-based study in Spain.

BACKGROUND: Research on the effectiveness of COVID-19 booster-based vaccine schedule is ongoing and real-world data on vaccine effectiveness (VE) in comorbid patients are limited. We aimed to estimate booster dose VE against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients. METHOD: A retrospective test-negative control study was undertaken in Galicia-Spain (December 2020-November 2021). VE and 95% confidence interval (CI) were estimated using multivariate logistic regression models. RESULTS: 1,512,415 (94.13%) negative and 94,334 (5.87%) positive SARS-CoV-2 test results were included. A booster dose of COVID-19 vaccine is associated with substantially higher protection against SARS-CoV-2 infection than vaccination without a booster [VEboosted = 87% (95%CI: 83%; 89%); VEnon-boosted = 66% (95%CI: 65%; 67%)]. The high VE was observed in all ages, but was more pronounced in subjects older than 65 years. VE against COVID-19 severity was analyzed in a mixed population of boosted and non-boosted individuals and considerable protection was obtained [VE: hospitalization = 72% (95%CI: 68%; 75%); intensive care unit administration = 83% (95%CI: 78%; 88%), in-hospital mortality = 66% (95%CI: 53%; 75%)]. Boosted comorbid patients are more protected against SARS-CoV-2 infection than those who were non-boosted. This was observed in a wide range of major diseases including cancer (81% versus 54%), chronic obstructive pulmonary disease (84% versus 61%), diabetes (84% versus 65%), hypertension (82% versus 65%) and obesity (91% versus 67%), among others. CONCLUSIONS: A booster dose of COVID-19 vaccine increases the protection against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients.

Evaluation of BNT162b2 Vaccine Effectiveness in Galicia, Northwest Spain.

Investigating vaccine effectiveness (VE) in real-world conditions is crucial, especially its variation across different settings and populations. We undertook a test-negative control study in Galicia (Northwest Spain) to assess BNT162b2 effectiveness against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as well as COVID-19 associated hospitalization, intensive care unit (ICU) admission and mortality. A total of 44,401 positive and 817,025 negative SARS-CoV-2 test results belonging to adults were included. Adjusted odds ratios of vaccination and their 95% confidence interval (CI) were estimated using multivariate logistic-regression models. BNT162b2 showed high effectiveness in reducing SARS-CoV-2 infections in all age categories, reaching maximum VE ≥ 14 days after administering the second dose [18-64 years: VE = 92.9% (95%CI: 90.2-95.1); 65-79 years: VE = 85.8% (95%CI: 77.3-91.9), and ≥80 years: VE = 91.4% (95%CI: 87.9-94.1)]. BNT162b2 also demonstrated effectiveness in preventing COVID-19 hospitalization for all age categories, with VE more pronounced for those aged ≥80 years [VE = 60.0% (95%CI: 49.4-68.3)]. Moreover, there was a considerable reduction in ICU admission [VE = 88.0% (95%CI: 74.6-95.8)] and mortality [VE = 38.0% (95%CI: 15.9-55.4)] in the overall population. BNT162b2 showed substantial protection against SARS-CoV-2 infections and COVID-19 severity. Our findings would prove useful for systematic reviews and meta-analysis on COVID-19 VE.

Método químico simplificado de desmineralización del esmalte dental humano / Simplified chemical method of demineralization in human dental enamel

Introducción: Se requieren métodos experimentales abreviados para simular las lesiones de desmineralización temprana de forma controlada y reproducible. Objetivo: Realizar una evaluación in vitro de un método simple de desmineralización incipiente del esmalte. Métodos: Estudio experimental aleatorizado con doble diseño factorial de réplicas. Se seleccionaron 12 terceros molares de sujetos humanos saludables para su desmineralización en solución de ácido láctico racémico. Las muestras se distribuyeron aleatoriamente: Grupo 1 (G1) (n= 6) ácido láctico a pH 2,4 y Grupo 2 (G2) (n= 6) ácido láctico a pH 5,4. A continuación, cada grupo se subdividió (n = 2) para evaluar el efecto de las soluciones a tres tiempos de exposición (7, 15 y 30 días) a 37 °C. La evaluación se llevó a cabo con estereomicroscopios, equipo de radiografía digital con un software de análisis digital de imágenes y microscopía de polarización. Se formuló una integración de los índices de respuesta y se realizó un ANOVA. Resultados: Los hallazgos visuales, radiográficos e histológicos mostraron que en el G1 en los tiempos 1 a 3, la desmineralización se caracterizó por una gran pérdida de la integridad del esmalte (80 por ciento a 100 por ciento). Visualmente, el G2 a los 7 días mostró opacidad y pérdida de brillo (16 por ciento) con preservación de la estructura superficial del esmalte. Conclusiones: Se demuestra que el empleo de ácido láctico durante 7 días a pH 5,4 produce una lesión clínica, radiográfica e histológica similar a una lesión temprana del esmalte(AU)

Introduction: Abridged experimental methods are required to simulate early demineralizing lesions in a controlled and reproducible way. Objective: Perform an in vitro evaluation of a simple method of incipient enamel demineralization. Methods: Randomized experimental study with a double factorial replication design. Twelve third molars from healthy human subjects were selected for demineralization in a racemic lactic acid solution. Samples were then distributed randomly: Group 1 (G1) (n= 6) lactic acid at pH 2.4 and Group 2 (G2) (n= 6) lactic acid at pH 5.4. Each group was then subdivided (n = 2) to evaluate the effect of the solutions at three exposure times (7, 15 and 30 days) at 37°C. The evaluation used stereomicroscopes, a digital x-rays apparatus with software for the digital analysis of images, and polarization microscopy. An integration of the response indices was formulated and ANOVA was performed. Results: Visual, radiographic and histological findings showed that G1 at time 1 through 3 displayed demineralization characterized by extensive loss (80 percent to 100 percent) of enamel integrity. Visually, G2 at 7 days exhibited opacity and loss of brightness (16 percent), with preservation of the surface structure of the enamel. Conclusions: It was shown that employing lactic acid for 7 days at pH 5.4 develops a clinical, radiographic and histological injury similar to an early enamel lesion(AU)

Método químico simplificado de desmineralización del esmalte dental humano / Simplified chemical method of demineralization in human dental enamel

Introducción: Se requieren métodos experimentales abreviados para simular las lesiones de desmineralización temprana de forma controlada y reproducible. Objetivo: Realizar una evaluación in vitro de un método simple de desmineralización incipiente del esmalte. Métodos: Estudio experimental aleatorizado con doble diseño factorial de réplicas. Se seleccionaron 12 terceros molares de sujetos humanos saludables para su desmineralización en solución de ácido láctico racémico. Las muestras se distribuyeron aleatoriamente: Grupo 1 (G1) (n= 6) ácido láctico a pH 2,4 y Grupo 2 (G2) (n= 6) ácido láctico a pH 5,4. A continuación, cada grupo se subdividió (n = 2) para evaluar el efecto de las soluciones a tres tiempos de exposición (7, 15 y 30 días) a 37 °C. La evaluación se llevó a cabo con estereomicroscopios, equipo de radiografía digital con un software de análisis digital de imágenes y microscopía de polarización. Se formuló una integración de los índices de respuesta y se realizó un ANOVA. Resultados: Los hallazgos visuales, radiográficos e histológicos mostraron que en el G1 en los tiempos 1 a 3, la desmineralización se caracterizó por una gran pérdida de la integridad del esmalte (80 por ciento a 100 por ciento). Visualmente, el G2 a los 7 días mostró opacidad y pérdida de brillo (16 por ciento) con preservación de la estructura superficial del esmalte. Conclusiones: Se demuestra que el empleo de ácido láctico durante 7 días a pH 5,4 produce una lesión clínica, radiográfica e histológica similar a una lesión temprana del esmalte(AU)

Introduction: Abridged experimental methods are required to simulate early demineralizing lesions in a controlled and reproducible way. Objective: Perform an in vitro evaluation of a simple method of incipient enamel demineralization. Methods: Randomized experimental study with a double factorial replication design. Twelve third molars from healthy human subjects were selected for demineralization in a racemic lactic acid solution. Samples were then distributed randomly: Group 1 (G1) (n= 6) lactic acid at pH 2.4 and Group 2 (G2) (n= 6) lactic acid at pH 5.4. Each group was then subdivided (n = 2) to evaluate the effect of the solutions at three exposure times (7, 15 and 30 days) at 37°C. The evaluation used stereomicroscopes, a digital x-rays apparatus with software for the digital analysis of images, and polarization microscopy. An integration of the response indices was formulated and ANOVA was performed. Results: Visual, radiographic and histological findings showed that G1 at time 1 through 3 displayed demineralization characterized by extensive loss (80 percent to 100 percent) of enamel integrity. Visually, G2 at 7 days exhibited opacity and loss of brightness (16 percent), with preservation of the surface structure of the enamel. Conclusions: It was shown that employing lactic acid for 7 days at pH 5.4 develops a clinical, radiographic and histological injury similar to an early enamel lesion(AU)

Variación de patrones morfológicos craneofaciales en relaciones esqueléticas Clase I, II y III / Variation of craniofacial morphological patterns in Class I, II, and III skeletal relationships

Introducción: tradicionalmente, los estudios de variaciones morfológicas de componentes craneofaciales para clasificar relaciones esqueléticas han considerado análisis univariados y multivariados mediante variables como distancias, ángulos y planos referenciales. Sin embargo, estos métodos no explican cambios generales de forma y proporcionan una descripción parcial y localizada de estas relaciones. En tanto, los métodos basados en Morfometría Geométrica (MG) en dos o tres dimensiones (2D o 3D,) permiten una comprensión detallada y un examen más sensible de variables. El objetivo fue identificar la variación de patrones morfológicos de la estructura CraneofacialGeneral(CFG) en relaciones esqueléticas I, II y III, utilizando MG-2D. Métodos: se hizo un estudio prospectivo mediante muestreo no probabilístico. Se tomaron 272 radiografías laterales de cráneo (140 hombres/132 mujeres) de individuos colombianos entre 17 y 25 años, y se determinó el error intraexaminador considerando la prueba F-ANOVA como estadístico de prueba. Se hizo Análisis Generalizado de Procrustes (AGP) y detección de datos atípicos por Cuantil Adaptativo. La variación en tamaño se analizó con prueba Kruskal-Wallis, considerando la matriz de Tamaño Centroide (CS) y las diferencias conformacionales con MANOVA. La identificación de patrones craneofaciales se determinó mediante Análisis de Componentes Principales (ACP) y Conglomerados/K-medias. Resultados: en la estructura CFG se encontraron diferencias conformacionales y una capacidad de buena clasificación del 89% (Clase I), 89% (Clase II) y 91% (Clase III). Se identificaron cuatro patrones craneofaciales; tres evidenciaron relaciones esqueléticas clásicas, y el otro identificó un nuevo grupo combinado de Clase I/II. Conclusiones: las diferencias morfológicas en los cuatro patrones identificados fueron evidentes, la MG permitió una visualización explicativa de patrones de variación morfológica, localizando sitios reales en donde ocurren cambios en tamaño y conformación.

Introduction: the studies on morphological variations of craniofacial components to classify skeletal relationships have traditionally included univariate and multivariate analysis using variables such as distances, angles, and reference planes. However, these methods fail to explain general changes in shape and provide partial localized descriptions of these relationships. Whereas methods using two- or threedimensional (2D or 3D) Geometric Morphometrics (GM) allow a detailed understanding and a more sensitive test of variables. The objective of this study was to identify morphological pattern variations of the Overall Craniofacial Structure (OCS) in skeletal relationships I, II, and III using GM-2D. Methods: this was a prospective study using non-probability sampling. It implied taking 272 lateral radiographs of the head of Colombian individuals (140 males/132 females) aged 17 to 25 years, determining intra-examiner error and using F-ANOVA as statistic test. Generalized Procrustes Analysis (GPA) was conducted as well as atypical data detection by Adaptive Quantile. Size variation was analyzed by the Kruskal-Wallis test considering Centroid Size matrix (CS) and conformational differences were analyzed with MANOVA. Craniofacial patterns were identified by Principal Components Analysis (PCA) and K-means/cluster. Results: the OCS showed conformational differences and a good classification capacity of 89% (Class I), 89% (Class II), and 91% (Class III). Four craniofacial patterns were identified; three of them showed typical skeletal relationships and the other pointed out to a new Class I/II combined group. Conclusions: the morphological differences in the four identified patterns were evident; GM allowed an explanatory display of morphological variation patterns, identifying actual sites where changes in size and shape take place.

Curvas de crecimiento del perímetro cefálico en niños de 0 a 3 años: una nueva aproximación / Head circumference growth curves in children 0 to 3 years of age: a new approach

Introducción: el perímetro cefálico es un indicador de salud y de crecimiento global craneal en la primera infancia, por lo que debe monitorearse. Usualmente, los patrones de referencia OMS utilizan el modelo Box Cox Power exponential y el método LMS para modelar el comportamiento del crecimiento del perímetro cefálico. Estos métodos tienen la debilidad de comparar cada individuo frente a una mediana poblacional, lo cual no permite caracterizar el crecimiento individual; en tanto que al usar los modelos longitudinales de efectos mixtos se puede evaluar el patrón individual de crecimiento y controlar la variabilidad entre sujetos. El objetivo fue hacer uso de los modelos longitudinales de efectos mixtos, caracterizar los patrones de crecimiento a partir del perímetro cefálico en niños de 0 a 3 años. Métodos: siendo éste un estudio longitudinal prospectivo, los criterios de elegibilidad para los niños obedecieron a factores de inclusión y exclusión (OMS); 265 niños colombianos (116 niñas, 149 niños), residentes en Bogotá, fueron distribuidos en 3 grupos G1: (0-12], G2: (12–24], G3: (24–36] meses. Se midieron cada 3 meses durante 1 año. Dos examinadores tuvieron entrenamiento y continua estandarización, monitoreo de adherencia a procedimientos de recolección y calidad de datos. Se calculó el error aleatorio y sistemático. Las curvas de crecimiento fueron construidas usando los modelos longitudinales mixtos. Para la estimación del modelo se utilizó el método de estimación de máxima verosimilitud restringida (REML), software estadístico R versión libre 2.15. Para el ajuste de los modelos el paquete lme4. Resultados: se ajustaron 6 modelos, observándose mayor pendiente de crecimiento de 0-12 meses. Conclusiones: la metodología utilizada permitió entender el comportamiento del perímetro cefálico por grupo, edad y sexo, y analizar datos con estructuras de desbalance.

Introduction: head circumference is an indicator of health and global cranial growth in early childhood, so it must be monitored. Usually, the WHO reference patterns use the Box Cox Power exponential model and the LMS method to model the behavior of head circumference growth. These methods are limited because they compare each individual against the median of a population, which prevents characterizing individual growth, while mixed-effect longitudinal models allow assessing individual growth patterns and controlling variability among subjects. The objective of this study was to use mixed-effect longitudinal models to characterize growth patterns based on head circumference in children 0 to 3 years of age. Methods: being a prospective longitudinal study, the criteria for children eligibility considered inclusion and exclusion factors (WHO); 265 Colombian children (116 girls, 149 boys) living in Bogotá were distributed in 3 groups: G1: (0-12], G2: (12-24], G3: (24-36] months. They were measured every 3 months for 1 year. Two examiners were trained and continuously standardized, and they were monitored on adherence to data quality and data collection procedures. Random and systematic errors were calculated. Growth curves were constructed using mixed longitudinal models. The model was estimated through the method of estimation of restricted maximum likelihood (REML), free R statistical software, version 2.15. To adjust the models, we used the lme4 package. Results: 6 models were adjusted, with maximum gradient of growth from 0 to 12 months. Conclusions: this methodology allowed understanding the behavior of head circumference by age group and sex, and analyzing data with unbalanced structures.

Changes in plasma membrane lipids, aquaporins and proton pump of broccoli roots, as an adaptation mechanism to salinity.

Salinity stress is known to modify the plasma membrane lipid and protein composition of plant cells. In this work, we determined the effects of salt stress on the lipid composition of broccoli root plasma membrane vesicles and investigated how these changes could affect water transport via aquaporins. Brassica oleracea L. var. Italica plants treated with different levels of NaCl (0, 40 or 80mM) showed significant differences in sterol and fatty acid levels. Salinity increased linoleic (18:2) and linolenic (18:3) acids and stigmasterol, but decreased palmitoleic (16:1) and oleic (18:1) acids and sitosterol. Also, the unsaturation index increased with salinity. Salinity increased the expression of aquaporins of the PIP1 and PIP2 subfamilies and the activity of the plasma membrane H(+)-ATPase. However, there was no effect of NaCl on water permeability (P(f)) values of root plasma membrane vesicles, as determined by stopped-flow light scattering. The counteracting changes in lipid composition and aquaporin expression observed in NaCl-treated plants could allow to maintain the membrane permeability to water and a higher H(+)-ATPase activity, thereby helping to reduce partially the Na(+) concentration in the cytoplasm of the cell while maintaining water uptake via cell-to-cell pathways. We propose that the modification of lipid composition could affect membrane stability and the abundance or activity of plasma membrane proteins such as aquaporins or H(+)-ATPase. This would provide a mechanism for controlling water permeability and for acclimation to salinity stress.