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ABSTRACT In the 21st century, several emergent viruses have posed a global threat. Each pathogen has emphasized the value of rapid and scalable vaccine development programs. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made the importance of such efforts especially clear. New biotechnological advances in vaccinology allow for recent advances that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns. During the COVID-19 pandemic, these DNA and RNA vaccines have facilitated the development and deployment of vaccines at an unprecedented pace. This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics: the genome of SARS-CoV-2 was available as early as January 2020, facilitating global efforts in the development of DNA and RNA vaccines within 2 weeks of the international community becoming aware of the new viral threat. Additionally, these technologies that were previously only theoretical are not only safe but also highly efficacious. Although historically a slow process, the rapid development of vaccines during the COVID-19 crisis reveals a major shift in vaccine technologies. Here, we provide historical context for the emergence of these paradigm-shifting vaccines. We describe several DNA and RNA vaccines in terms of their efficacy, safety, and approval status. We also discuss patterns in worldwide distribution. The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last 2 decades in particular and suggest a new era in vaccines against emerging pathogens. IMPORTANCE The SARS-CoV-2 pandemic has caused untold damage globally, presenting unusual demands on but also unique opportunities for vaccine development. The development, production, and distribution of vaccines are imperative to saving lives, preventing severe illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Although vaccine technologies that provide the DNA or RNA sequence of an antigen had never previously been approved for use in humans, they have played a major role in the management of SARS-CoV-2. In this review, we discuss the history of these vaccines and how they have been applied to SARS-CoV-2. Additionally, given that the evolution of new SARS-CoV-2 variants continues to present a significant challenge in 2022, these vaccines remain an important and evolving tool in the biomedical response to the pandemic. more...

ABSTRACT Over the past 150 years, vaccines have revolutionized the relationship between people and disease. During the COVID-19 pandemic, technologies such as mRNA vaccines have received attention due to their novelty and successes. However, more traditional vaccine development platforms have also yielded important tools in the worldwide fight against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of approaches have been used to develop COVID-19 vaccines that are now authorized for use in countries around the world. In this review, we highlight strategies that focus on the viral capsid and outwards, rather than on the nucleic acids inside. These approaches fall into two broad categories: whole-virus vaccines and subunit vaccines. Whole-virus vaccines use the virus itself, in either an inactivated or an attenuated state. Subunit vaccines contain instead an isolated, immunogenic component of the virus. Here, we highlight vaccine candidates that apply these approaches against SARS-CoV-2 in different ways. In a companion article (H. M. Rando, R. Lordan, L. Kolla, E. Sell, et al., mSystems 8:e00928-22, 2023, https://doi.org/10.1128/mSystems.00928-22), we review the more recent and novel development of nucleic acid-based vaccine technologies. We further consider the role that these COVID-19 vaccine development programs have played in prophylaxis at the global scale. Well-established vaccine technologies have proved especially important to making vaccines accessible in low- and middle-income countries. Vaccine development programs that use established platforms have been undertaken in a much wider range of countries than those using nucleic acid-based technologies, which have been led by wealthy Western countries. Therefore, these vaccine platforms, though less novel from a biotechnological standpoint, have proven to be extremely important to the management of SARS-CoV-2. IMPORTANCE The development, production, and distribution of vaccines is imperative to saving lives, preventing illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Vaccines that use cutting-edge biotechnology have played an important role in mitigating the effects of SARS-CoV-2. However, more traditional methods of vaccine development that were refined throughout the 20th century have been especially critical to increasing vaccine access worldwide. Effective deployment is necessary to reducing the susceptibility of the world’s population, which is especially important in light of emerging variants. In this review, we discuss the safety, immunogenicity, and distribution of vaccines developed using established technologies. In a separate review, we describe the vaccines developed using nucleic acid-based vaccine platforms. From the current literature, it is clear that the well-established vaccine technologies are also highly effective against SARS-CoV-2 and are being used to address the challenges of COVID-19 globally, including in low- and middle-income countries. This worldwide approach is critical for reducing the devastating impact of SARS-CoV-2. more...

COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). more...

Abstract Pediatric type 2 diabetes mellitus (T2DM) patients are often overweight or obese, yet there are no validated clinical measures of adiposity to stratify cardiometabolic risk in this population. The tri-ponderal mass index (TMI, kg/m3) has recently been reported as a measure of adiposity in children, but there has been no validation of the association of TMI with adiposity in pediatric T2DM. We hypothesized that in children with T2DM, the TMI can serve as a more accurate measure of adiposity when compared to BMI z-score, and that it is associated with components of the metabolic syndrome. This is a cross-sectional secondary data analysis from the Improving Renal Complications in Adolescents with Type 2 Diabetes Through REsearch (iCARE) study (n = 116, age 10.20–17.90 years). Spearman’s correlations and multivariable regression were used in the analyses. When compared to DXA, TMI demonstrated significant correlation with total adiposity versus BMI z-score (TMI r = 0.74, p-value more...

Contexto: Las relaciones de género transversalizan todos los procesos que se desarrollan en la vida de los seres humanos. La cooperativización en Cuba y en especial en el municipio de Camagüey es de gran importancia para dinamizar la economía e impulsar las técnicas productivas en este sector; la participación de mujeres y hombres en el mismo revierte gran significación. Objetivo identificar las manifestaciones en las relaciones de género a través de los resultados de la investigación realizada en dos cooperativas del municipio camagüeyano y lograr disminuir o erradicar las brechas existentes para el logro de un desarrollo equitativo, estable y sostenido en este sector de la economía cubana. Métodos: En la investigación se utilizó una perspectiva metodológica (cuantitativa y cualitativa) Se manejó la observación no participante lo cual permitió una mirada integradora del fenómeno que se estudió al complementar los datos cuantificables. Se aplicó entrevista a los presidentes de ambas cooperativas y se realizaron cuatro historias de vida, a dos mujeres y a dos hombres de cada Cooperativa de Créditos y Servicios. Se empleó una encuesta con 21 ítems, en condiciones adecuadas. En la investigación se realizaron todos los análisis estadísticos con IBN SPSS versión 23-2015. Conclusiones: El estudio corroboró que existen manifestaciones que se comportan como brechas en las relaciones de género que deben ser analizadas, así como proponer acciones para su disminución o eliminación. more...

Context: Gender relations involve every human process. The creation of cooperatives in Cuba, especially in the municipality of Camagüey, is critical to dynamize the economy and promote productive techniques in the sector; the participation of men and women in this process is highly significant. Objective: to identify manifestations of gender relations through the outcome of research conducted in two cooperatives in the municipality of Camagüey, and reduce or eradicate the existing breaches that hinder equitable, stable, and sustained development in that sector of the Cuban economy. Methods: A methodological approach (quantitative and qualitative) was used in the research. Non-participatory observation was used as well, which enabled a comprehensive glance of this aspect, by complementing quantifiable data. The presidents of both cooperatives were interviewed, and the life records of four members (two men and two women) were written. A 21-item survey was applied under the right conditions. Every statistical analysis was made using IBN SPSS, version 23-2015. Conclusions: This study corroborated the existence of manifestations, such as breaches in gender relations which should be addressed, and to propose actions for reduction or elimination. more...

Introduction: tetralogy of Fallot with pulmonary valve agenesis is a complex congenital heart disease, with a prevalence of 2-6%, frequently associated with chromosomopathies. Case report: 2-month-old male infant diagnosed on the fourth day of birth with Tetralogy of Fallot with pulmonary valve agenesis. He presented with a clinical picture characterized by respiratory symptoms such as dyspnea, mild distal cyanosis, dry cough, slight subcostal and intercostal initially, which evolved into a picture of metabolic alkalosis compensating for respiratory acidosis, with frequent events of bronchospasm due to compression of the bronchi by dilatation of the trunk and branches of the pulmonary artery. Treatment was clinical, symptom management. Mechanical ventilation in prone position, treatment with diuretics for hypertension and intravenous inotropic drugs were required. The patient died at 3 months of life. Conclusions: tetralogy of Fallot with pulmonary valve agenesis is a complex, infrequent and potentially fatal entity, where patient survival is determined by complete primary correction of the defect, mainly before the onset of respiratory symptoms, and the infrequency and complexity of its management make this congenital heart disease a challenge for the medical community. A deep and continuous study of atypical heart disease is necessary to achieve better medical care. more...

Background: First Nations (FN) women have a higher risk of diabetes than non-FN women in Canada. Prenatal education and breastfeeding may reduce the risk of diabetes in mothers and offspring. The rates of breastfeeding initiation and participation in the prenatal program are low in FN communities. Methods: A prenatal educational website, social media-assisted prenatal chat groups and community support teams were developed in three rural or remote FN communities in Manitoba. The rates of participation of pregnant women in prenatal programs and breastfeeding initiation were compared before and after the start of the remote prenatal education program within 2014-2017. Findings: The participation rate of FN pregnant women in rural or remote communities in the prenatal program and breastfeeding initiation during 1-year after the start of the community-based remote prenatal education program were significantly increased compared to that during 1-year before the start of the program (54% versus 36% for the participation rate, 50% versus 34% for breastfeeding initiation, p more...

ABSTRACT The enterococci, which are among the leading causes of multidrug-resistant (MDR) hospital infection, are notable for their environmental ruggedness, which extends to intrinsic antibiotic resistance. To identify genes that confer this unique property, we used Tn-seq to comprehensively explore the genome of MDR Enterococcus faecalis strain MMH594 for genes important for growth in nutrient-containing medium and with low-level antibiotic challenge. As expected, a large core of genes for DNA replication, expression, and central metabolism, shared with other bacteria, are intolerant to transposon disruption. However, genes were identified that are important to E. faecalis that are either absent from or unimportant for Staphylococcus aureus and Streptococcus pneumoniae fitness when similarly tested. Further, 217 genes were identified that when challenged by sub-MIC antibiotic levels exhibited reduced tolerance to transposon disruption, including those previously shown to contribute to intrinsic resistance, and others not previously ascribed this role. E. faecalis is one of the few Gram-positive bacteria experimentally shown to possess a functional Entner-Doudoroff pathway for carbon metabolism, a pathway that contributes to stress tolerance in other microbes. Through functional genomics and network analysis we defined the unusual structure of this pathway in E. faecalis and assessed its importance. These approaches also identified toxin-antitoxin and related systems that are unique and active in E. faecalis. Finally, we identified genes that are absent in the closest nonenterococcal relatives, the vagococci, and that contribute importantly to fitness with and without antibiotic selection, advancing an understanding of the unique biology of enterococci. IMPORTANCE Enterococci are leading causes of antibiotic-resistant infection transmitted in hospitals. The intrinsic hardiness of these organisms allows them to survive disinfection practices and then proliferate in the gastrointestinal tracts of antibiotic-treated patients. The objective of this study was to identify the underlying genetic basis for its unusual hardiness. Using a functional genomic approach, we identified traits and pathways of general importance for enterococcal survival and growth that distinguish them from closely related pathogens as well as ancestrally related species. We further identified unique traits that enable them to survive antibiotic challenge, revealing a large set of genes that contribute to intrinsic antibiotic resistance and a smaller set of uniquely important genes that are rare outside enterococci. more...

Introducción: El Síndrome Coronario Agudo es considerado una complicación de la ateroesclerosis con alta morbilidad y mortalidad en ambos sexos. Tiene un importante impacto socioeconómico evidenciado en los años de vida potencial perdidos.Objetivo: Caracterizar por clínica y angiografía a mujeres y hombres diagnosticados con Síndrome Coronario Agudo. Material y Métodos: Se realizó un estudio descriptivo de diseño transversal con 214 pacientes, del Servicio de Cardiología del Hospital Universitario “Manuel Ascunce Doménech” de Camagüey, desde enero de 2015 hasta enero de 2017. La fuente primaria estuvo dada por el informe escrito de los resultados de la coronariografía realizada en el Cardiocentro “Ernesto Che Guevara” de Villa Clara y las historias clínicas hospitalarias de cada paciente; se llenó un formulario con las siguientes variables: grupos de edades, sexo, factores de riesgo, forma clínica de presentación, resultado coronariográfico y conducta médica. Este documento se computarizó, se aplicaron pruebas de significación estadística y los resultados se ilustraron en tablas.Resultados: Predominaron los hombres, edad mayor de 60 años, la hipertensión arterial fue el factor de riesgo coronario de mayor representatividad para ambos sexos y se afectó de manera significativa la arteria descendente anterior.Conclusiones: A medida que avanza la edad las mujeres tienen igual o más riesgo que los hombres de sufrir enfermedad arterial coronaria, pues en ambos se incrementa la exposición a los predictores de riesgo. Las diferencias en las formas de expresión clínica, angiográfica y percepción de la enfermedad, determinan las estrategias de intervención y conducta médica. more...

New collection records for Anthophorula micheneri (Timberlake, 1947) from Loudoun County and other locations in Virginia, USA document an approximately 1,350 km extension of its previously recorded geographic range. New state records for the rarely seen Hylaeus sparsus (Cresson, 1869) collected in Giles County and from a blue vane trap in Loudoun County, Virginia add to our knowledge of this species’ range and phenology in the USA. Floral records for both species are documented with a discussion of possible host preferences. more...

BackgroundSurvivors of physical and emotional trauma experience enduring occupational, psychological and quality of life impairments. Examining survivors from a large fire provides a unique opportunity to distinguish the impact of physical and emotional trauma on long-term outcomes. The objective is to detail the multi-dimensional long-term effects of a large fire on its survivor population and assess differences in outcomes between survivors with and without physical injury.Methods and findingsThis is a survey-based cross-sectional study of survivors of The Station fire on February 20, 2003. The relationships between functional outcomes and physical injury were evaluated with multivariate regression models adjusted for pre-injury characteristics and post-injury outcomes. Outcome measures include quality of life (Burn Specific Health Scale-Brief), employment (time off work), post-traumatic stress symptoms (Impact of Event Scale-Revised) and depression symptoms (Beck Depression Inventory). 104 fire survivors completed the survey; 47% experienced a burn injury. There was a 42% to 72% response rate range. Although depression and quality of life were associated with burn injury in univariate analyses (pConclusionsSurvivors of this large fire experienced significant life disruption, including occupational, psychological and quality of life sequelae. The findings suggest that quality of life, depression and post-traumatic stress outcomes are related to emotional trauma, not physical injury. However, physical injury is correlated with employment outcomes. The long-term impact of this traumatic event underscores the importance of longitudinal and mental health care for trauma survivors, with attention to those with and without physical injuries. more...