Age-specific predictors of disease severity in children with respiratory syncytial virus infection beyond infancy and through the first 5 years of age.

BACKGROUND: Respiratory syncytial virus (RSV) infection is associated with significant morbidity in infants. Risk factors for severe disease beyond the first 2 years of life have not been fully defined. METHODS: Children <5 years hospitalized with virologically confirmed RSV infection were identified over six respiratory seasons (10/2012-4/2018) and their medical records manually reviewed. Multivariable analyses were performed to define the age-specific (<6, 6-24, and >24-59 months) risk factors associated with oxygen administration, PICU admission, mechanical ventilation, and duration of hospitalization. RESULTS: We identified 5143 children hospitalized with RSV infection: 53.5% (n = 2749) <6 months; 31.7% (n = 1631) 6-24 months; and 14.8% (n = 763) >24-59 months. Rates of ICU admission were high (35%-36%) and comparable across age groups, while children >24-59 and 6-24 versus those <6 months required supplemental oxygen more frequently (73%; 71%; 68%, respectively; p = .003). The presence of comorbidities increased with age (25%, <6 months; 46%, 6-24 months; 70%, >24-59 months; p < .001). Specifically, neuromuscular disorders, chronic lung disease, and reactive airway disease/asthma were predictive of worse clinical outcomes in children aged 6-24 and >24-59 months, while RSV-viral codetections increased the risk of severe outcomes in children aged <6 and 6-24 months of age. CONCLUSIONS: Almost half of children hospitalized with RSV infection were >6 months. Underlying comorbidities increased with age and remained associated with severe disease in older children, while RSV-viral codetections were predictive of worse clinical outcomes in the youngest age groups. These data suggest the importance of defining the clinical phenotype associated with severe RSV according to age, and the persistent burden associated with RSV beyond infancy.

CACPPAF, a COMSOL application to characterize polyelectrolyte properties of actin filaments.

We present an interactive COMSOL web application that allows both expert and non-expert users to numerically evaluate the electric potential, ionic concentration distribution, velocity profile, and ionic current along a molecular structure surface characterizing actin filaments. This online computational and visualization tool runs on a high performance server (http://marucholab.physics.utsa.edu:2036), that enables users to perform multiple analyses and comparisons without compromising computational resources. As a unique feature, the multiphysics formulation accounts for the filament surface roughness, the finite filament size, and the ionic condensation, providing a deeper understanding of the electrochemical phenomena taking place at the interface between the irregular charged shape of the filament and its biological environment. Overall, the interactive component allows investigators to characterize polyelectrolyte properties of healthy and abnormal actin filaments in physiological and pathological conditions.

Molecular structure study on the polyelectrolyte properties of actin filaments.

An accurate characterization of the polyelectrolyte properties of actin filaments might provide a deeper understanding of the fundamental mechanisms governing the intracellular ionic wave packet propagation in neurons. Infinitely long cylindrical models for actin filaments and approximate electrochemical theories for the electrolyte solutions were recently used to characterize these properties in in vitro and intracellular conditions. This article uses a molecular structure model for actin filaments to investigate the impact of roughness and finite size on the mean electrical potential, ionic density distributions, currents, and conductivities. We solved the electrochemical theories numerically without further approximations. Our findings bring new insights into the electrochemical interactions between a filament's irregular surface charge density and the surrounding medium. The irregular shape of the filament structure model generated pockets, or hot spots, where the current density reached higher or lower magnitudes than those in neighboring areas throughout the filament surface. It also revealed the formation of a well-defined asymmetric electrical double layer with a thickness larger than that commonly used for symmetric models.

Characterization of thermal and optical properties in porcine pancreas tissue.

BACKGROUND: Photothermal therapies have shown promise for treating pancreatic ductal adenocarcinoma when they can be applied selectively, but off-target heating can frustrate treatment outcomes. Improved strategies leveraging selective binding and localized heating are possible with precision medical approaches such as functionalized gold nanoparticles, but careful control of optical dosage and thermal generation would be imperative. However, the literature review revealed many groups assume liver properties for pancreas tissue or rely on insufficiently rigorous characterization studies. OBJECTIVE: The objective of this study was to determine the thermal conductivity and optical properties at 808/1064 nm wavelengths in healthy samples of fresh and frozen porcine pancreas ex vivo. METHODS: Thermal conductivity of the porcine pancreas tissue was measured by utilizing a hot plate and two K-type thermocouples. Experimental variables such as tissue sample thickness, hot plate temperature, and heat convection coefficient were estimated through the control experiments utilizing specimens with known thermal conductivity. Optical evaluations assessed light attenuation at the 808 and 1064 nm wavelengths (continuous wave, collimated beam) by measuring the light transmittance and reflectance of different tissue thicknesses. In turn, these measurements were input into an inverse adding-doubling program to estimate the optical absorption and reduced scattering coefficients. RESULTS: Interestingly, pancreas tissue thermal conductivity was demonstrated to have no significant difference (p > 0.5) between samples that were fresh, frozen for 7 days, or frozen for 14 days. Conversely, optical property assessment exhibited a significant difference (p < 0.001) between fresh and frozen tissue samples, with increased absorbance and reflectance within the frozen group. However, the optical attenuation values measured were substantially less than that of the liver or reported in previous pancreas studies, suggesting a wide overestimation of these properties. CONCLUSIONS: These thermal and optical properties are critical to the development of novel therapeutic strategies like plasmonic photothermal therapy, but perhaps more importantly, are invaluable towards informing better surgical planning and operative technique among the existing thermal approaches for treating pancreas tissue.

Clinical differentiation of inflammatory bowel disease (IBD) in Latin America and the Caribbean.

ABSTRACT: The aim of the present study was to describe the epidemiological and clinical characteristics of inflammatory bowel disease (IBD), including medical and surgical treatments, in several countries in Latin America and the Caribbean.IBD is recognized as a global health problem because its incidence and prevalence have increased significantly over the last few years.This multicenter retrospective cohort study included 4714 patients with IBD diagnosed from 9 countries in Latin America and the Caribbean: Colombia, Cuba, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela.Crohn disease (CD) was more frequent in Puerto Rico (71.9%), the Dominican Republic (61.0%), and Peru (53.1%). Ulcerative colitis was more frequent in Colombia (78.6%), Venezuela (78.2%), Mexico (75.5%), Cuba (69.9%), Ecuador (64.1%), and Uruguay (60.9%). The following clinical characteristics were more frequent in the Caribbean: penetrating behavior in CD, steroid dependence, steroid resistance, intolerance to thiopurines, extraintestinal manifestations, surgeries, hospitalizations due to IBD, and family history of IBD. The factors associated with the use of biological therapy were pancolitis in ulcerative colitis, penetrating behavior in CD, steroid resistance and dependence, presence of extraintestinal manifestations, and the need for surgery.This study from Latin America and the Caribbean demonstrated the different epidemiological and clinical characteristics of IBD.

Cemetery Relocations in Hidroituango: An Interdisciplinary Study.

This study realized the exhumation and transfer of human remains buried in the cemeteries at Orobajo, Barbacoas and La Fortuna (Municipality of Sabanalarga, Peque and Buriticá respectively) within the framework of "Social Management" of the Ituango Hydroelectric Project and the program Integral Restitution of Living Conditions for communities. Methods and techniques from bioanthropology, forensic sciences, archeology and Soil Sciences were used. Cemeteries were characterized by unconventional burials; moreover, documentation of tombs and burial practices were not generalized, nor did they show patterns. In the field assessment, 2,883 pit tests and soil probes using a penetrometer were carried out over a total area of 2,288 square meters. A total of 349 skeletonized human remains were exhumed, almost double of what was expected; of these, 180 were from Orabajo, 151 from Barbacoas, and 18 from La Fortuna. Though the remains showed a great deal of deterioration, age at death was determined for 59% of cases, and sex identified in 49%. Personal artifacts and clothing items were recovered along with the bones in many cases. Remains from Barbacoas and La Fortuna were given over to communities, and final dispositions were made in sites previously agreed upon (cemeteries in Peque, Buriticá and Sabanalarga respectively).

Assessment and Modeling of Plasmonic Photothermal Therapy Delivered via a Fiberoptic Microneedle Device Ex Vivo.

Plasmonic photothermal therapy (PPTT) has potential as a superior treatment method for pancreatic cancer, a disease with high mortality partially attributable to the currently non-selective treatment options. PPTT utilizes gold nanoparticles infused into a targeted tissue volume and exposed to a specific light wavelength to induce selective hyperthermia. The current study focuses on developing this approach within an ex vivo porcine pancreas model via an innovative fiberoptic microneedle device (FMD) for co-delivering light and gold nanoparticles. The effects of laser wavelengths (808 vs. 1064 nm), irradiances (20-50 mW·mm-2), and gold nanorod (GNR) concentrations (0.1-3 nM) on tissue temperature profiles were evaluated to assess and control hyperthermic generation. The GNRs had a peak absorbance at ~800 nm. Results showed that, at 808 nm, photon absorption and subsequent heat generation within tissue without GNRs was 65% less than 1064 nm. The combination of GNRs and 808 nm resulted in a 200% higher temperature rise than the 1064 nm under similar conditions. A computational model was developed to predict the temperature shift and was validated against experimental results with a deviation of <5%. These results show promise for both a predictive model and spatially selective, tunable treatment modality for pancreatic cancer.

Urban soils as a spatial indicator of quality for urban socio-ecological systems.

The development of criteria and indicators to quantify the transition to sustainability of the urban socio-ecological systems quality is determinant for planning policies and the 21st century urban agenda. This study models the spatial variation in the concentration and distribution of some macronutrients, micronutrients, and trace nutrients in the soil of a high-altitude city in the Andes. Meanwhile, machine learning methods were employed to study some interactions between the different dimensions that constitute an urban socio-ecosystem that caused these variations. We proposed a methodology that considered two phases: a) field work to collect data on 300 soil samples; laboratory analysis to measure the concentrations of 24 macronutrients, micronutrients, and trace nutrients; and the design of geophysical, spectral, and urban co-variables; b) statistical and geo-informatics analysis, where multivariate analysis grouped the elements into factors; and, machine learning integrated with co-variables was applied to derive the intensity of each factor across the city. Multivariate statistics described the variation in soil co-concentrations with a moderate percentage (42%). Four factors were determined that grouped some of the analyzed elements, as follows: F1 (Zn, S, Cu, Pb, Ni, and Cr), F2 (Ba, Ag, K, In, and Mg), F3 (B, V, Li, and Sr), and F4 (Si and Mn). The percentage R2 out-of-bag of the spatial model were: F1 = 20%, F2 = 8%, F3 = 14%, and F4 = 10%. Our outputs show that the enrichment and contamination by anthropogenic factors, such as the increase in population density, land use, road network, and traffic generated by fossil fuel vehicles, should be prioritized in urban planning decisions.

The effect of national protest in Ecuador on PM pollution.

Particulate matter (PM) accounts for millions of premature deaths in the human population every year. Due to social and economic inequality, growing human dissatisfaction manifests in waves of strikes and protests all over the world, causing paralysis of institutions, services and circulation of transport. In this study, we aim to investigate air quality in Ecuador during the national protest of 2019, by studying the evolution of PM2.5 (PM ≤ 2.5 µm) concentrations in Ecuador and its capital city Quito using ground based and satellite data. Apart from analyzing the PM2.5 evolution over time to trace the pollution changes, we employ machine learning techniques to estimate these changes relative to the business-as-usual pollution scenario. In addition, we present a chemical analysis of plant samples from an urban park housing the strike. Positive impact on regional air quality was detected for Ecuador, and an overall - 10.75 ± 17.74% reduction of particulate pollution in the capital during the protest. However, barricade burning PM peaks may contribute to a release of harmful heavy metals (tire manufacture components such as Co, Cr, Zn, Al, Fe, Pb, Mg, Ba and Cu), which might be of short- and long-term health concerns.

Immune profiles provide insights into respiratory syncytial virus disease severity in young children.

Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a "safe and protective" immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients). Additionally, only infants with severe disease had increased numbers of HLA-DRlow monocytes, not present in outpatients. Multivariable analyses confirmed that IFN overexpression was associated with decreased odds of hospitalization, whereas increased numbers of HLA-DRlow monocytes were associated with increased risk of hospitalization. These findings suggest that robust innate immune responses are associated with mild RSV infection in infants.

Multiphysics Modeling of Plasmonic Photothermal Heating Effects in Gold Nanoparticles and Nanoparticle Arrays.

Induced hyperthermia has been demonstrated as an effective oncological treatment due to the reduced heat tolerance of most malignant tissues; however, most techniques for heat generation within a target volume are insufficiently selective, inducing heating and unintended damage to surrounding healthy tissues. Plasmonic photothermal therapy (PPTT) utilizes light in the near-infrared (NIR) region to induce highly localized heating in gold nanoparticles, acting as exogenous chromophores, while minimizing heat generation in nearby tissues. However, optimization of treatment parameters requires extensive in vitro and in vivo studies for each new type of pathology and tissue targeted for treatment, a process that can be substantially reduced by implementing computational modeling. Herein, we describe the development of an innovative model based on the finite element method (FEM) that unites photothermal heating physics at the nanoscale with the micron scale to predict the heat generation of both single and arrays of gold nanoparticles. Plasmonic heating from laser illumination is computed for gold nanoparticles with three different morphologies: nanobipyramids, nanorods, and nanospheres. Model predictions based on laser illumination of nanorods at a visible wavelength (655 nm) are validated through experiments, which demonstrate a temperature increase of 5 °C in the viscinity of the nanorod array when illuminated by a 150 mW red laser. We also present a predictive model of the heating effect induced at 810 nm, wherein the heating efficiencies of the various morphologies sharing this excitation peak are compared. Our model shows that the nanorod is the most effective at heat generation in the isolated scenario, and arrays of 91 nm long nanorods reached hyperthermic levels (an increase of at least 5 °C) within a volume of over 20 µm3.

Lesiones premalignas y malignas del estómago en pacientes sin tamización para cáncer gástrico / Premalignant and malignant findings of the stomach in patients without gastric cancer screening

Introducción. Para establecer una frecuencia de seguimiento como método de tamización en cáncer gástrico, se propone la endoscopia en pacientes mayores de 35 años con síntomas de dispepsia, y en pacientes mayores de 40 años con alto riesgo. La demora en la realización de la primera endoscopia en la vida de un paciente incrementa el riesgo de no detectar lesiones premalignas ni cáncer potencialmente prevenible. Los objetivos de nuestro estudio fueron describir el número de pacientes mayores de 40 años con endoscopia de primera vez y evaluar la presencia de lesiones premalignas y malignas del estómago en pacientes sin tamización. Métodos. Revisión retrospectiva de base de datos. Se describieron hallazgos de informes de histopatología en pacientes mayores de 40 años (lesiones premalignas y malignas). Adicionalmente se describieron las variables sociodemográficas de los pacientes con endoscopia de primera vez y la presencia de infección por Helicobacter pylori en la población mencionada. Resultados. Setenta y ocho pacientes (23,6 %) tuvieron una endoscopia de primera vez siendo mayores de 40 años. En el 44 % de los pacientes se encontró la presencia de Helicobacter pylori, 25,4 % de los pacientes presentaron atrofia gástrica, 23,1 % metaplasia, ningún paciente presentó displasia y un paciente (1,3 %) presentó un adenocarcinoma gástrico. Discusión. Los resultados de nuestro estudio muestran un número elevado de pacientes sin endoscopia de tamización. Nuestro estudio resalta la importancia del uso de la endoscopia de tamización en la prevención, así como en el diagnóstico temprano de cáncer gástrico y sugiere mayor adherencia a las guías de práctica clínica

Introduction. To establish a frequency of follow-up as a screening method for gastric cancer, endoscopy is pro-posed in patients older than 35 years with symptoms of dyspepsia, and in patients older than 40 years at high risk. The delay in performing the first endoscopy in a patient's life increases the risk of not detecting premalignant lesions or potentially preventable cancer. The aims of our study were to describe the number of patients older than 40 years with first-time endoscopy and to assess the presence of premalignant and malignant stomach lesions in patients without screening.Methods. Retrospective database review. Histopathology report findings in patients older than 40 years (prema-lignant and malignant lesions) were described. Additionally, the sociodemographic variables of patients with first-time endoscopy and the presence of Helicobacter pylori infection in the mentioned population were described.Results. Seventy-eight patients (23.6%) had a first-time endoscopy being older than 40 years. Helicobacter pylori was found in 44% of the patients, 25.4% of the patients had gastric atrophy, 23.1% had metaplasia, no patient had dysplasia and one patient (1.3%) had gastric adenocarcinoma. Discusions. The results of our study show a high number of patients without screening endoscopy. Our study highlights the importance of the use of screening endoscopy in prevention, as well as in the early diagnosis of gastric cancer, and suggests greater adherence to clinical practice guidelines

Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.

BACKGROUND: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood. METHODS: We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer. RESULTS: Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for < 6 months vs ≥ 6 months showed significant enrichment of Notch signaling pathway genes, along with a trend for enrichment for luminal progenitor gene signature similar to what is observed in BRCA1 mutation carriers and basal-like breast tumors. CONCLUSIONS: We report here for the first time that forced or abrupt involution of the mammary glands following pregnancy and lack of breastfeeding results in expansion of luminal progenitor cells, higher inflammation, proliferation, and ductal hyperplasia, a known risk factor for developing breast cancer.

Recent Trends in RSV Immunoprophylaxis: Clinical Implications for the Infant.

Respiratory syncytial virus (RSV) remains the leading cause for hospitalizations in infants worldwide, resulting in significant health and financial burden. Since 1998, the humanized monoclonal antibody palivizumab remains the only available option licensed for the prevention of severe RSV disease in high-risk children, namely premature infants and those with chronic lung disease and congenital heart disease. In 2014, the American Academy of Pediatrics modified the recommendations on the use of RSV prophylaxis in these high-risk children, and limited its use to premature infants born at < 28 weeks' gestational age (wGA). Following this last guidance update, studies have confirmed that premature infants of 29 to 34 wGA remain at high risk for severe RSV disease, especially those of younger chronologic age. New and more cost-effective strategies are being developed that would help alleviate both the health and financial burden associated with severe RSV disease.

Calidad de vida en pacientes con enfermedad inflamatoria intestinal atendidos en tres hospitales del Seguro Social en Ecuador (Quito, Guayaquil y Cuenca) / Quality of life in patients with inflammatory disease bowel treated at three Social Security hospitals in Ecuador (Quito, Guayaquil and Cuenca)

Contexto: la enfermedad inflamatoria intestinal (EII) es un proceso inflamatorio crónico del intestino con sus dos variedades, la colitis ulcerativa (CU) y la enfermedad de Crohn (EC). El objetivo del tratamiento es la remisión clínica y endoscópica de la enfermedad, sin embargo, la calidad de vida que esta influye en el manejo y evolución de la enfermedad es usualmente soslayada. Objetivo: determinar la calidad de vida y los factores relacionados en pacientes con EII atendidos en tres hospitales del Seguro Social ecuatoriano. Metodología: estudio observacional, descriptivo y transversal en pacientes mayores de 18 años diagnosticados de EII, que acuden al servicio de gastroenterología de tres hospitales del Seguro Social: Carlos Andrade Marín, José Carrasco Arteaga y Teodoro Maldonado, en el periodo enero a junio de 2018. Resultados: se evaluaron 50 pacientes, 68% (n=34) con CU y 32% (n=16) con EC. La edad promedio fue 48 +/-9 para CU y 42+/-7 en EC. Se determinó una relación hombre: mujer de 1,6:1. El 30% de los pacientes evaluados (n=15) percibieron su calidad de vida como baja. Se encontró diferencias estadísticamente significativa en relación al tipo de EII (EC, p 0,03), sexo femenino (p 0,04) y presencia de recaídas (p 0,04). Conclusión: la calidad de vida en los pacientes con enfermedad inflamatoria intestinal fue percibida como más baja en pacientes de sexo femenino que quienes padecen EC y en quienes presentan uno o más episodios de recaídas durante el último semestre.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory process of the intestine with its two varieties, ulcerative colitis and Crohn's. The goal of treatment is the clinical and endoscopic remission of the disease. However, the quality of life that influences the management and evolution of the disease is usually overlooked. Aim: To determine the quality of life and related factors in patients with IBD treated in three hospitals of Ecuadorian Social Security. Methods: Epidemiological, observational, descriptive and cross-sectional study in patients over 18 years of age diagnosed with IBD, who attend the gastroenterology service of three hospitals: Carlos Andrade Marin, Jose Carrasco Arteaga and Teodoro Maldonado, in the period January to June 2018. Results: 50 patients were evaluated, 68% (n=34) with UC and 32% (n=16) with CD. The average age was 48 +/- 9 years for CU and 42+/- 7 years in CD. A male female ratio of 1.6: 1 was determined. 30% of the patients evaluated (n=15) perceived their quality of life as low. Statistically significant differences were found in relation to the type of IBD (CD, p 0.03), female sex (p 0.04) and the presence of relapses (p 0.04). Conclusions: The quality of life in patients with inflammatory bowel disease was perceived as lower in female patients than those with CD and in those with one or more relapse episodes during the last semester.