391 results on '"Kalergis, Alexis M."'
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2. Co-administration of recombinant BCG and SARS-CoV-2 proteins leads to robust antiviral immunity
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Ramírez, Mario A., Loaiza, Ricardo A., Martínez-Balboa, Yohana, Bruneau, Nicole, Ramírez, Eugenio, González, Pablo A., Bueno, Susan M., and Kalergis, Alexis M.
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- 2024
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3. A molecular perspective for the development of antibodies against the human respiratory syncytial virus
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Loaiza, Ricardo A., Ramírez, Robinson A., Sepúlveda-Alfaro, Javiera, Ramírez, Mario A., Andrade, Catalina A., Soto, Jorge A., González, Pablo A., Bueno, Susan M., and Kalergis, Alexis M.
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- 2024
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4. Is there a role for herpes simplex virus type 1 in multiple sclerosis?
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Duarte, Luisa F., Gatica, Sebastian, Castillo, Almendra, Kalergis, Alexis M., Bueno, Susan M., Riedel, Claudia A., and González, Pablo A.
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- 2023
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5. Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults
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Rojas, Álvaro, Navarrete, María Soledad, Del Río, Constanza, Del Pino, Dinely, Aguirre, Natalia, Salinas, Grecia, Vega, Franco, Salgado, Acsa, Quinteros, Thomas, Ortiz, Marlene, Puente, Marcela, Muñoz, Alma, Astudillo, Patricio, Le Corre, Nicole, Potin, Marcela, Catalán, Juan, Peralta, Melan, Zamanillo, Consuelo, Keller, Nicole, Fernández, Rocío, Aljaro, Sofía, López, Sofía, González, José Tomás, Weil, Tania, Opazo, Luz, Muñoz, Paula, Estay, Inés, Cantillana, Miguel, Carrera, Liliana, Masalleras, Matías, Guzmán, Paula, Aguirre, Francisca, Cortés, Aarón, Bátiz, Luis Federico, Pérez, Javiera, Apablaza, Karen, Yates, Lorena, Valdés, María de los Ángeles, Hurtado, Bernardita, Venteneul, Veronique, Astorga, Constanza, Muñoz-Venturelli, Paula, Vial, Pablo A., Schilling, Andrea, Pavez, Daniela, Pérez, Inia, Riviotta, Amy, González, Francisca, Urrutia, Francisca, Del Río, Alejandra, Asenjo, Claudia, Vargas, Bárbara, Castro, Francisca, Acuña, Alejandra, Guzmán, Javiera, Astudillo, Camila, Pérez, Carlos M., Espinoza, Pilar, Martínez, Andrea, Arancibia, Marcela, Romero, Harold, Bustamante, Cecilia, Pérez, María Loreto, Uribe, Natalia, Silva, Viviana, Morice, Bernardita, Pérez, Marco, González, Marcela, Jensen, Werner, Pasten, Claudia, Aguilera, M. Fernanda, Martínez, Nataly, Molina, Camila, Arrieta, Sebastián, López, Begoña, Ortiz, Claudia, Escobar, Macarena, Bustamante, Camila, Espinoza, Marcia, Pardo, Angela, Carrasco, Alison, Montes, Miguel, Saldías, Macarena, Gutiérrez, Natalia, Sánchez, Juliette, Fuentes, Daniela, Calvo, Yolanda, Cepeda, Mariela, Lemus, Rosario, Suárez, Muriel, Armijo, Mercedes, Monsalves, Shirley, Marucich, Constance, Cornejo, Cecilia, Acosta, Ángela, Prado, Xaviera, Yáñez, Francisca, Barroeta, Marisol, López, Claudia, Donato, Paulina, Lasso, Martin, Iturrieta, María, Giraldo, Juan, Gutiérrez, Francisco, Acuña, María, Cascone, Ada, Rojas, Raymundo, Sepúlveda, Camila, Contreras, Mario, Campisto, Yessica, González, Pablo, Quizhpi, Zoila, López, Mariella, Pizzeghello, Vania, Silva, Stephannie, Méndez, Constanza, Peñaloza, Hernán F., Schultz, Bárbara M., Piña-Iturbe, Alejandro, Ríos, Mariana, Moreno-Tapia, Daniela, Pereira-Sánchez, Patricia, Leighton, Diane, Orellana, Claudia, Covarrubias, Consuelo, Gálvez, Nicolás M.S., Soto, Jorge A., Duarte, Luisa F., Rivera-Pérez, Daniela, Vázquez, Yaneisi, Cabrera, Alex, Bustos, Sergio, Iturriaga, Carolina, Urzua, Marcela, Navarrete, María S., Fasce, Rodrigo A., Fernández, Jorge, Mora, Judith, Ramírez, Eugenio, Gaete-Argel, Aracelly, Acevedo, Mónica, Valiente-Echeverría, Fernando, Soto-Rifo, Ricardo, Weiskopf, Daniela, Grifoni, Alba, Sette, Alessandro, Zeng, Gang, Meng, Weining, González-Aramundiz, José V., González, Pablo A., Abarca, Katia, Melo-González, Felipe, Bueno, Susan M., and Kalergis, Alexis M.
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- 2023
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6. Involvement of trained immunity during autoimmune responses
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Mora, Valentina P., Loaiza, Ricardo A., Soto, Jorge A., Bohmwald, Karen, and Kalergis, Alexis M.
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- 2023
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7. SARS-CoV-2 vaccine booster in solid organ transplant recipients previously immunised with inactivated versus mRNA vaccines: A prospective cohort study
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Dib, Martín, Le Corre, Nicole, Ortiz, Catalina, García, Daniel, Ferrés, Marcela, Martinez-Valdebenito, Constanza, Ruiz-Tagle, Cinthya, Ojeda, María José, Espinoza, Manuel A., Jara, Aquiles, Arab, Juan Pablo, Rabagliati, Ricardo, Vizcaya, Cecilia, Ceballos, María Elena, Sarmiento, Mauricio, Mondaca, Sebastián, Viñuela, Macarena, Pastore, Antonia, Szwarcfiter, Vania, Galdames, Elizabeth, Barrera, Aldo, Castro, Pablo, Gálvez, Nicolás MS, Soto, Jorge A., Bueno, Susan M., Kalergis, Alexis M., Nervi, Bruno, and Balcells, M. Elvira
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- 2022
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8. BCG vaccination induces cross-protective immunity against pathogenic microorganisms
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Soto, Jorge A., Gálvez, Nicolás M.S., Andrade, Catalina A., Ramírez, Mario A., Riedel, Claudia A., Kalergis, Alexis M., and Bueno, Susan M.
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- 2022
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9. Influence of online opinions and interactions on the Covid-19 vaccination in Chile
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Villegas, Claudio, Ortiz, Abril, Arriagada, Víctor, Ortega, Sofía, Walker, Juan, Arriagada, Eduardo, Kalergis, Alexis M., and Huepe, Cristián
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- 2022
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10. 4th booster-dose SARS-CoV-2 heterologous and homologous vaccination in rheumatological patients.
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Gallardo-Nelson, Maria Jose, Cruces, Marcos, Gómez, Yolanda M., Fuenzalida, Constanza, Silva, Javiera, Aravena-Traipi, Laura, Nuñez, Eduardo, Gaete-Angel, Aracelly, Rivas-Yañez, Elizabeth, Kalergis, Alexis M., Soto-Rifo, Ricardo, and Valiente-Echeverria, Fernando
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SARS-CoV-2 Omicron variant ,COVID-19 vaccines ,HUMORAL immunity ,SYSTEMIC scleroderma ,SYSTEMIC lupus erythematosus - Abstract
Objective: to evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine's immune response. Methods: We designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed. Results: Performing a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p<0.05) in the level of the ID
50 , both for healthy controls and for patients with IMRDs. The humoral response of patients with IMRDs is significantly lower compared to healthy controls for the Omicron variant of SARS-CoV-2 (p = 0.0015). The humoral response of patients with IMRDs decreases significantly when the time interval between vaccination and sample collection is greater than 35 days. This difference was observed in the response, both for the Wuhan variant and for the Omicron variant. Conclusion: The IMRDs patients, the humoral response variation in the SARS-CoV-2 vaccine depends on doses and type of vaccine administered, the humoral response times and the treatment that these patients are receiving. [ABSTRACT FROM AUTHOR]- Published
- 2024
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11. Immunogenicity and Safety of a Quadrivalent Influenza Vaccine in Population Aged 3 Years and Older in Chile and the Philippines: A Phase 3, Non-Inferiority, Double-Blind, Randomized Controlled Clinical Trial.
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Yang, Wanqi, González, Pablo A., Xin, Qianqian, Reyes, Mari Rose De Los, Villalobos, Ralph Elvi, Borja-Tabora, Charissa Fay Corazon, Bermal, Nancy Nazaire, Kalergis, Alexis M., Yu, Dan, Wu, Wenbin, Bueno, Susan M., Huo, Liqun, Calvo, Mario, Zeng, Gang, and Li, Jing
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CLINICAL trials ,VACCINE safety ,INFLUENZA vaccines ,CONFIDENCE intervals ,IMMUNE response - Abstract
Objectives: In this study, we aimed to evaluate the non-inferiority of a quadrivalent influenza vaccine (QIV) developed by Sinovac Biotech Co., Ltd. (Sinovac, Beijing, China) by comparing its immunogenicity and safety with a comparator QIV (Vaxigrip Tetra
® ) in a population aged 3 years and older in Chile and the Philippines. Methods: A phase 3, non-inferiority, double-blind, randomized controlled, multicenter clinical trial was conducted in the southern hemisphere (SH) 2023 influenza season. Participants aged ≥ 3 years old with stable health were randomized 1:1 to receive either Sinovac QIV or comparator QIV. The co-primary outcomes were immunological non-inferiority for Sinovac QIV versus the comparator against each strain contained in the vaccines in terms of seroconversion rates (SCRs) and geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies 28 days after final vaccination. Results: A total of 2039 participants were vaccinated (1019 Sinovac QIV; 1020 comparator QIV). Sinovac QIV induced non-inferior immune responses to all four strains as compared to comparator QIV, with slightly higher GMTs than those of comparator QIV: GMT ratios (lower limit 95% confidence interval (CI)) were 1.8 (1.6) for A(H1N1), 1.4 (1.3) for A (H3N2), 1.3 (1.1) for B Victoria and 1.2 (1.1) for B Yamagata; observed seroconversion rate differences (lower limit 95% CI) were 9.6% (6.7) for A(H1N1), 7.0% (3.5) for A(H3N2), 2.4% (−0.03) for B Victoria and 6.8% (3.0) for B Yamagata. Adverse reactions were similar across the two groups and no vaccine-related serious adverse events were reported. Conclusions: The immunogenicity of Sinovac QIV was non-inferior to that of the comparator QIV in these populations aged 3 years and older, and safety was comparable. [ABSTRACT FROM AUTHOR]- Published
- 2024
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12. Neurological Impact of Respiratory Viruses: Insights into Glial Cell Responses in the Central Nervous System.
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Mora, Valentina P., Kalergis, Alexis M., and Bohmwald, Karen
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RESPIRATORY syncytial virus ,NEUROGLIA ,VIRUS diseases ,CENTRAL nervous system ,MICROGLIA ,SARS-CoV-2 - Abstract
Respiratory viral infections pose a significant public health threat, particularly in children and older adults, with high mortality rates. Some of these pathogens are the human respiratory syncytial virus (hRSV), severe acute respiratory coronavirus-2 (SARS-CoV-2), influenza viruses (IV), human parvovirus B19 (B19V), and human bocavirus 1 (HBoV1). These viruses cause various respiratory symptoms, including cough, fever, bronchiolitis, and pneumonia. Notably, these viruses can also impact the central nervous system (CNS), leading to acute manifestations such as seizures, encephalopathies, encephalitis, neurological sequelae, and long-term complications. The precise mechanisms by which these viruses affect the CNS are not fully understood. Glial cells, specifically microglia and astrocytes within the CNS, play pivotal roles in maintaining brain homeostasis and regulating immune responses. Exploring how these cells interact with viral pathogens, such as hRSV, SARS-CoV-2, IVs, B19V, and HBoV1, offers crucial insights into the significant impact of respiratory viruses on the CNS. This review article examines hRSV, SARS-CoV-2, IV, B19V, and HBoV1 interactions with microglia and astrocytes, shedding light on potential neurological consequences. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Lung pathology due to hRSV infection impairs blood–brain barrier permeability enabling astrocyte infection and a long-lasting inflammation in the CNS
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Bohmwald, Karen, Soto, Jorge A., Andrade-Parra, Catalina, Fernández-Fierro, Ayleen, Espinoza, Janyra A., Ríos, Mariana, Eugenin, Eliseo A., González, Pablo A., Opazo, María Cecilia, Riedel, Claudia A., and Kalergis, Alexis M.
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- 2021
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14. Safety and immunogenicity evaluation of recombinant BCG vaccine against respiratory syncytial virus in a randomized, double-blind, placebo-controlled phase I clinical trial
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Abarca, Katia, Rey-Jurado, Emma, Muñoz-Durango, Natalia, Vázquez, Yaneisi, Soto, Jorge A., Gálvez, Nicolás M.S., Valdés-Ferrada, Javier, Iturriaga, Carolina, Urzúa, Marcela, Borzutzky, Arturo, Cerda, Jaime, Villarroel, Luis, Madrid, Victoria, González, Pablo A., González-Aramundiz, José V., Bueno, Susan M., and Kalergis, Alexis M.
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- 2020
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15. New insights into the pathogenesis of SARS-CoV-2 during and after the COVID19 pandemic.
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Carvajal, Jonatan J., García-Castillo, Valeria, Cuellar, Shelsy V., Campillay-Véliz, Claudia P., Salazar-Ardiles, Camila, Avellaneda, Andrea M., Muñoz, Christian A., Retamal-Díaz, Angello, Bueno, Susan M., González, Pablo A., Kalergis, Alexis M., and Lay, Margarita K.
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SARS-CoV-2 ,PULMONARY fibrosis ,COVID-19 - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient’s overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.
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González-Madrid, Enrique, Rangel-Ramírez, Ma. Andreina, Opazo, María C., Méndez, Luis, Bohmwald, Karen, Bueno, Susan M., González, Pablo A., Kalergis, Alexis M., and Riedel, Claudia A.
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PROTEIN expression ,PHENOTYPES ,HYPOTHYROIDISM ,GESTATIONAL age ,AUTISM spectrum disorders ,HORMONE synthesis ,GESTATIONAL diabetes ,THYROID gland function tests - Abstract
Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTXoffspring displayed elevated proinflammatory cytokines in blood, including IL-1β, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1- like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Controloffspring. Notably, the supplementation with T
4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASDlike outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy. [ABSTRACT FROM AUTHOR]- Published
- 2024
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17. Natural killer T cells in allergic asthma: implications for the development of novel immunotherapeutical strategies.
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Gutiérrez-Vera, Cristián, García-Betancourt, Richard, Palacios, Pablo A., Müller, Marioly, Montero, David A., Verdugo, Carlos, Ortiz, Francisca, Simon, Felipe, Kalergis, Alexis M., González, Pablo A., Saavedra-Avila, Noemi A., Porcelli, Steven A., and Carreño, Leandro J.
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CYTOTOXIC T cells ,KILLER cells ,ASTHMA ,ALLERGIES ,IMMUNE response - Abstract
Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Respiratory Syncytial Virus Vaccines: Analysis of Pre-Marketing Clinical Trials for Immunogenicity in the Population over 50 Years of Age.
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Papazisis, Georgios, Topalidou, Xanthippi, Gioula, Georgia, González, Pablo A., Bueno, Susan M., and Kalergis, Alexis M.
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RESPIRATORY syncytial virus ,VIRAL vaccines ,IMMUNE response ,OLDER people ,CLINICAL trials - Abstract
Immunosenescence refers to age-related alterations in immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on the vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV) that include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 42. Our preliminary evaluation of published results and interim analyses of RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Allergens of the urushiol family promote mitochondrial dysfunction by inhibiting the electron transport at the level of cytochromes b and chemically modify cytochrome c1
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Pacheco, Rodrigo, Quezada, Sergio A., Kalergis, Alexis M., Becker, María Inés, Ferreira, Jorge, and De Ioannes, Alfredo E.
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- 2021
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20. Cellular immune response induced by surface immunogenic protein with AbISCO-100 adjuvant vaccination decreases group B Streptococcus vaginal colonization
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Soto, Jorge A., Diaz-Dinamarca, Diego A., Soto, Daniel A., Barrientos, Magaly J., Carrión, Flavio, Kalergis, Alexis M., and Vasquez, Abel E.
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- 2019
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21. Oral infectivity through carnivorism in murine model of Trypanosoma cruzi infection.
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Torres, Víctor, Contreras, Víctor, Gutiérrez, Bessy, San Francisco, Juan, Catalán, Alejandro, Luis Vega, José, Kyung-Mee Moon, Foster, Leonard J., de Almeida, Rafael F., Kalergis, Alexis M., and González, Jorge
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TRYPANOSOMA cruzi ,CYSTEINE proteinases ,PEPSIN ,NEURAMINIDASE ,GASTRIC mucosa ,AMASTIGOTES ,MONOCLONAL antibodies - Abstract
Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (~6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60-100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Pathophysiological, immunological, and inflammatory features of long COVID.
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Bohmwald, Karen, Diethelm-Varela, Benjamín, Rodríguez-Guilarte, Linmar, Rivera, Thomas, Riedel, Claudia A., González, Pablo A., and Kalergis, Alexis M.
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POST-acute COVID-19 syndrome ,ACUTE diseases ,SYMPTOMS ,COVID-19 pandemic ,COVID-19 ,CANCER fatigue - Abstract
The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social and economic burdens on nations. While most of the attention and therapeutic efforts have concentrated on the acute phase of the disease, a notable proportion of survivors experience persistent symptoms post-infection clearance. This diverse set of symptoms, loosely categorized as long COVID, presents a potential additional public health crisis. It is estimated that 1 in 5 COVID-19 survivors exhibit clinical manifestations consistent with long COVID. Despite this prevalence, the mechanisms and pathophysiology of long COVID remain poorly understood. Alarmingly, evidence suggests that a significant proportion of cases within this clinical condition develop debilitating or disabling symptoms. Hence, urgent priority should be given to further studies on this condition to equip global public health systems for its management. This review provides an overview of available information on this emerging clinical condition, focusing on the affected individuals' epidemiology, pathophysiological mechanisms, and immunological and inflammatory profiles. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Human metapneumovirus respiratory infection affects both innate and adaptive intestinal immunity.
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Sepúlveda-Alfaro, Javiera, Catalán, Eduardo A., Vallejos, Omar P., Ramos-Tapia, Ignacio, Madrid-Muñoz, Cristóbal, Mendoza-León, María J., Suazo, Isidora D., Rivera-Asin, Elizabeth, Silva, Pedro H., Alvarez-Mardones, Oscar, Castillo-Godoy, Daniela P., Riedel, Claudia A., Schinnerling, Katina, Ugalde, Juan A., Soto, Jorge A., Bueno, Susan M., Kalergis, Alexis M., and Melo-Gonzalez, Felipe
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HUMAN metapneumovirus infection ,ANTIMICROBIAL peptides ,IMMUNOLOGIC memory ,GUT microbiome ,INTESTINES ,CALPROTECTIN ,BUTYRATES - Abstract
Introduction: Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Methods: Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. Results: We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level. Discussion: To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Differential Diagnosis in the Management of Acute Respiratory Infections through Point-of-Care Rapid Testing in a Post-Pandemic Scenario in Latin America: Special Focus on COVID-19, Influenza, and Respiratory Syncytial Virus.
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Alvarez-Moreno, Carlos Arturo, de Araújo, Evaldo Stanislau Affonso, Baumeister, Elsa, Nogales Crespo, Katya A., Kalergis, Alexis M., Muñoz Medina, José Esteban, Tsukayama, Pablo, and Ugarte-Gil, Cesar
- Subjects
ADULT respiratory distress syndrome ,RESPIRATORY syncytial virus ,POINT-of-care testing ,EPIDEMIOLOGY - Abstract
This review provides a comprehensive summary of evidence to explore the role and value of differential diagnosis in the management of Acute Respiratory Infections (ARIs) through point-of-care (POC) rapid testing in a post-pandemic scenario, paying particular attention to coronavirus disease 2019 (COVID-19), influenza, and respiratory syncytial virus (RSV). The document builds on a review of literature and policies and a process of validation and feedback by a group of seven experts from Latin America (LATAM). Evidence was collected to understand scientific and policy perspectives on the differential diagnosis of ARIs and POC rapid testing, with a focus on seven countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru. The evidence indicates that POC rapid testing can serve to improve ARI case management, epidemiological surveillance, research and innovation, and evidence-based decision-making. With multiple types of rapid tests available for POC, decisions regarding which tests to use require the consideration of the testing purpose, available resources, and test characteristics regarding accuracy, accessibility, affordability, and results turnaround time. Based on the understanding of the current situation, this document provides a set of recommendations for the implementation of POC rapid testing in LATAM, supporting decision-making and guiding efforts by a broad range of stakeholders. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring.
- Author
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Carlos Rivera, Juan, Opazo, Ma. Cecilia, Hernández-Armengol, Rosario, Álvarez, Oscar, José Mendoza-León, Marıa, Caamaño, Esteban, Gatica, Sebastian, Bohmwald, Karen, Bueno, Susan M., Gonzá lez, Pablo A., Neunlist, Michel, Boudin, Helene, Kalergis, Alexis M., and Riedel, Claudia A.
- Subjects
INFLAMMATORY bowel diseases ,HYPOTHYROIDISM ,ULCERATIVE colitis ,SODIUM sulfate ,DEXTRAN sulfate - Abstract
Introduction: Gestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring). Methods: Gestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10-E14. The HTXoffspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment. Results: The HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTXoffspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTXoffspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring. Discussion: Gestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTXoffspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. Understanding the Neurotrophic Virus Mechanisms and Their Potential Effect on Systemic Lupus Erythematosus Development.
- Author
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Uribe, Felipe R., González, Valentina P. I., Kalergis, Alexis M., Soto, Jorge A., and Bohmwald, Karen
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SYSTEMIC lupus erythematosus ,HUMAN herpesvirus 1 ,VIRUS diseases ,LYMPHOCYTIC choriomeningitis virus ,HERPES simplex virus ,CENTRAL nervous system viral diseases ,ADENOVIRUS diseases - Abstract
Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. The immune response elicited by neurotropic viruses in the CNS is commanded mainly by microglia, which, together with other local cells, can secrete inflammatory cytokines to fight the infection. The most relevant neurotropic viruses are adenovirus (AdV), cytomegalovirus (CMV), enterovirus (EV), Epstein–Barr Virus (EBV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2), lymphocytic choriomeningitis virus (LCMV), and the newly discovered SARS-CoV-2. Several studies have associated a viral infection with systemic lupus erythematosus (SLE) and neuropsychiatric lupus (NPSLE) manifestations. This article will review the knowledge about viral infections, CNS pathologies, and the immune response against them. Also, it allows us to understand the relevance of the different viral proteins in developing neuronal pathologies, SLE and NPSLE. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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27. Severe respiratory disease caused by human respiratory syncytial virus impairs language learning during early infancy
- Author
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Peña, Marcela, Jara, Cristina, Flores, Juan C., Hoyos-Bachiloglu, Rodrigo, Iturriaga, Carolina, Medina, Mariana, Carcey, Javier, Espinoza, Janyra, Bohmwald, Karen, Kalergis, Alexis M., and Borzutzky, Arturo
- Published
- 2020
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28. T Cell Receptor Binding Kinetics Required for T Cell Activation Depend on the Density of Cognate Ligand on the Antigen-Presenting Cell
- Author
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González, Pablo A., Carreño, Leandro J., Coombs, Daniel, Mora, Jorge E., Palmieri, Edith, Goldstein, Byron, Nathenson, Stanley G., and Kalergis, Alexis M.
- Published
- 2005
29. Endothelial-to-mesenchymal transition: Cytokine-mediated pathways that determine endothelial fibrosis under inflammatory conditions
- Author
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Pérez, Lorena, Muñoz-Durango, Natalia, Riedel, Claudia A., Echeverría, Cesar, Kalergis, Alexis M., Cabello-Verrugio, Claudio, and Simon, Felipe
- Published
- 2017
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30. A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice
- Author
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Céspedes, Pablo F., Rey-Jurado, Emma, Espinoza, Janyra A., Rivera, Claudia A., Canedo-Marroquín, Gisela, Bueno, Susan M., and Kalergis, Alexis M.
- Published
- 2017
- Full Text
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31. Development and analytical validation of real-time PCR for the detection of Streptococcus agalactiae in pregnant women
- Author
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Escobar, Daniel F., Diaz-Dinamarca, Diego A., Hernández, Carlos F., Soto, Daniel A., Manzo, Ricardo A., Alarcón, Pedro I., Pinto, Camila H., Bastias, Diego N., Oberg-Bravo, Carolayn N., Rojas, Robert, Illanes, Sebastián E., Kalergis, Alexis M., and Vasquez, Abel E.
- Published
- 2020
- Full Text
- View/download PDF
32. SEN1990 is a predicted winged helix-turn-helix protein involved in the pathogenicity of Salmonella enterica serovar Enteritidis and the expression of the gene oafB in the SPI-17.
- Author
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Hoppe-Elsholz, Guillermo, Piña-Iturbe, Alejandro, Vallejos, Omar P., Suazo, Isidora D., Sepúlveda-Alfaro, Javiera, Pereira-Sánchez, Patricia, Martínez-Balboa, Yohana, Catalán, Eduardo A., Reyes, Pablo, Scaff, Valentina, Bassi, Franco, Campos-Gajardo, Sofia, Avilés, Andrea, Santiviago, Carlos A., Kalergis, Alexis M., and Bueno, Susan M.
- Subjects
SALMONELLA enterica serovar enteritidis ,SALMONELLA enterica ,GENE expression ,DNA-binding proteins - Abstract
Excisable genomic islands (EGIs) are horizontally acquired genetic elements that harbor an array of genes with diverse functions. ROD21 is an EGI found integrated in the chromosome of Salmonella enterica serovar Enteritidis (Salmonella ser. Enteritidis). While this island is known to be involved in the capacity of Salmonella ser. Enteritidis to cross the epithelial barrier and colonize sterile organs, the role of most ROD21 genes remains unknown, and thus, the identification of their function is fundamental to understanding the impact of this EGI on bacterium pathogenicity. Therefore, in this study, we used a bioinformatical approach to evaluate the function of ROD21-encoded genes and delve into the characterization of SEN1990, a gene encoding a putative DNA-binding protein. We characterized the predicted structure of SEN1990, finding that this protein contains a three-stranded winged helix-turn-helix (wHTH) DNA-binding domain. Additionally, we identified homologs of SEN1990 among other members of the EARL EGIs. Furthermore, we deleted SEN1990 in Salmonella ser. Enteritidis, finding no differences in the replication or maintenance of the excised ROD21, contrary to what the previous Refseq annotation of the protein suggests. Highthroughput RNA sequencing was carried out to evaluate the effect of the absence of SEN1990 on the bacterium's global transcription. We found a downregulated expression of oafB, an SPI-17-encoded acetyltransferase involved in O-antigen modification, which was restored when the deletion mutant was complemented ectopically. Additionally, we found that strains lacking SEN1990 had a reduced capacity to colonize sterile organs in mice. Our findings suggest that SEN1990 encodes a wHTH domain-containing protein that modulates the transcription of oafB from the SPI-17, implying a crosstalk between these pathogenicity islands and a possible new role of ROD21 in the pathogenesis of Salmonella ser. Enteritidis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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33. Differential Severe Acute Respiratory Syndrome Coronavirus 2–Specific Humoral Response in Inactivated Virus–Vaccinated, Convalescent, and Breakthrough-Infected Subjects.
- Author
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Duarte, Luisa F, Vázquez, Yaneisi, Diethelm-Varela, Benjamín, Pavez, Valentina, Berríos-Rojas, Roslye, Méndez, Constanza, Riedel, Claudia A, White, Jessica A, Kalergis, Alexis M, Bueno, Susan M, and González, Pablo A
- Subjects
SARS-CoV-2 ,HUMORAL immunity ,CORONAVIRUSES ,BOOSTER vaccines ,VIRAL nonstructural proteins - Abstract
Background We sought to identify potential antigens for discerning between humoral responses elicited after vaccination with CoronaVac (a severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] inactivated vaccine), natural infection, or breakthrough infection. Methods Serum samples obtained from volunteers immunized with CoronaVac (2 and 3 doses), breakthrough case patients, and from convalescent individuals were analyzed to determine the immunoglobulin (Ig) G responses against 3 structural and 8 nonstructural SARS-CoV-2 antigens. Results Immunization with CoronaVac induced higher levels of antibodies against the viral membrane (M) protein compared with convalescent subjects both after primary vaccination and after a booster dose. Individuals receiving a booster dose displayed equivalent levels of IgG antibodies against the nucleocapsid (N) protein, similar to convalescent subjects. Breakthrough case patients produced the highest antibody levels against the N and M proteins. Antibodies against nonstructural viral proteins were present in >50% of the convalescent subjects. Conclusions Vaccinated individuals elicited a different humoral response compared to convalescent subjects. The analysis of particular SARS-CoV-2 antigens could be used as biomarkers for determining infection in subjects previously vaccinated with CoronaVac. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
34. Respiratory Syncytial Virus Vaccines: A Review of the Candidates and the Approved Vaccines.
- Author
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Topalidou, Xanthippi, Kalergis, Alexis M., and Papazisis, Georgios
- Subjects
RESPIRATORY syncytial virus ,VIRAL vaccines ,VACCINE approval ,MESSENGER RNA ,RESPIRATORY syncytial virus infection vaccines ,VACCINE development - Abstract
Respiratory syncytial virus (RSV) is responsible for a significant proportion of global morbidity and mortality affecting young children and older adults. In the aftermath of formalin-inactivated RSV vaccine development, the effort to develop an immunizing agent was carefully guided by epidemiologic and pathophysiological evidence of the virus, including various vaccine technologies. The pipeline of RSV vaccine development includes messenger ribonucleic acid (mRNA), live-attenuated (LAV), subunit, and recombinant vector-based vaccine candidates targeting different virus proteins. The availability of vaccine candidates of various technologies enables adjustment to the individualized needs of each vulnerable age group. Arexvy
® (GSK), followed by Abrysvo® (Pfizer), is the first vaccine available for market use as an immunizing agent to prevent lower respiratory tract disease in older adults. Abrysvo is additionally indicated for the passive immunization of infants by maternal administration during pregnancy. This review presents the RSV vaccine pipeline, analyzing the results of clinical trials. The key features of each vaccine technology are also mentioned. Currently, 24 vaccines are in the clinical stage of development, including the 2 licensed vaccines. Research in the field of RSV vaccination, including the pharmacovigilance methods of already approved vaccines, promotes the achievement of successful prevention. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
35. Opposing roles of IL-10 in acute bacterial infection
- Author
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Peñaloza, Hernán F., Schultz, Barbara M., Nieto, Pamela A., Salazar, Geraldyne A., Suazo, Isidora, Gonzalez, Pablo A., Riedel, Claudia A., Alvarez-Lobos, Manuel M., Kalergis, Alexis M., and Bueno, Susan M.
- Published
- 2016
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- View/download PDF
36. On Defining the Rules for Interactions between the T Cell Receptor and Its Ligand: A Critical Role for a Specific Amino Acid Residue of the T Cell Receptor β Chain
- Author
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Wang, Fuming, Ono, Toshiro, Kalergis, Alexis M., Zhang, Weijia, DiLorenzo, Teresa P., Lim, Kap, and Nathenson, Stanley G.
- Published
- 1998
37. Gestational Hypothyroxinemia Imprints a Switch in the Capacity of Astrocytes and Microglial Cells of the Offspring to React in Inflammation
- Author
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Opazo, María C., González, Pablo A., Flores, Betsi D., Venegas, Luis F., Albornoz, Eduardo A., Cisternas, Pablo, Bohmwald, Karen, Nieto, Pamela A., Bueno, Susan M., Kalergis, Alexis M., and Riedel, Claudia A.
- Published
- 2018
- Full Text
- View/download PDF
38. The Optimisation of the Expression of Recombinant Surface Immunogenic Protein of Group B Streptococcus in Escherichia coli by Response Surface Methodology Improves Humoral Immunity
- Author
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Díaz-Dinamarca, Diego A., Jerias, José I., Soto, Daniel A., Soto, Jorge A., Díaz, Natalia V., Leyton, Yessica Y., Villegas, Rodrigo A., Kalergis, Alexis M., and Vásquez, Abel E.
- Published
- 2018
- Full Text
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39. New insights about excisable pathogenicity islands in Salmonella and their contribution to virulence
- Author
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Nieto, Pamela A., Pardo-Roa, Catalina, Salazar-Echegarai, Francisco J., Tobar, Hugo E., Coronado-Arrázola, Irenice, Riedel, Claudia A., Kalergis, Alexis M., and Bueno, Susan M.
- Published
- 2016
- Full Text
- View/download PDF
40. Contribution of viral and bacterial infections to senescence and immunosenescence.
- Author
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Reyes, Antonia, Ortiz, Gerardo, Duarte, Luisa F., Fernández, Christian, Hernández-Armengol, Rosario, Palacios, Pablo A., Prado, Yolanda, Andrade, Catalina A., Rodriguez-Guilarte, Linmar, Kalergis, Alexis M., Simon, Felipe, Carreño, Leandro J., Riedel, Claudia A., Cáceres, Mónica, and González, Pablo A.
- Subjects
IMMUNOSENESCENCE ,CELLULAR aging ,BACTERIAL diseases ,VIRUS diseases ,COMMUNICABLE diseases ,DISEASE susceptibility ,HETEROCHROMATIN - Abstract
Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated β-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host’s susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
41. Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults.
- Author
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Pacheco, Gaspar A., Andrade, Catalina A., Gálvez, Nicolás M. S., Vázquez, Yaneisi, Rodríguez-Guilarte, Linmar, Abarca, Katia, González, Pablo A., Bueno, Susan M., and Kalergis, Alexis M.
- Subjects
RESPIRATORY syncytial virus ,CELLULAR immunity ,IMMUNOLOGIC memory ,PERFORINS ,NEWBORN infants ,COMPLEMENT (Immunology) ,BCG vaccines - Abstract
Introduction: The human respiratory syncytial virus (hRSV) is responsible for most respiratory tract infections in infants. Even though currently there are no approved hRSV vaccines for newborns or infants, several candidates are being developed. rBCG-N-hRSV is a vaccine candidate previously shown to be safe in a phase I clinical trial in adults (clinicaltrials.gov identifier #NCT03213405). Here, secondary immunogenicity analyses were performed on these samples. Methods: PBMCs isolated from immunized volunteers were stimulated with hRSV or mycobacterial antigens to evaluate cytokines and cytotoxic T cellderived molecules and the expansion of memory T cell subsets. Complement C1q binding and IgG subclass composition of serum antibodies were assessed. Results: Compared to levels detected prior to vaccination, perforin-, granzyme B-, and IFN-g-producing PBMCs responding to stimulus increased after immunization, along with their effector memory response. N-hRSV- and mycobacterial-specific antibodies from rBCG-N-hRSV-immunized subjects bound C1q. Conclusion: Immunization with rBCG-N-hRSV induces cellular and humoral immune responses, supporting that rBCG-N-hRSV is immunogenic and safe in healthy individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
42. Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases.
- Author
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José Mendoza-León, María, Mangalam, Ashutosh K., Regaldiz, Alejandro, González-Madrid, Enrique, Andreina Rangel-Ramírez, Maria, Álvarez-Mardonez, Oscar, Vallejos, Omar P., Méndez, Constanza, M. Bueno, Susan, Melo-González, Felipe, Duarte, Yorley, Cecilia Opazo, Maria, Kalergis, Alexis M., and Riedel, Claudia A.
- Subjects
SHORT-chain fatty acids ,THYROID diseases ,GUT microbiome ,MICROBIAL metabolites ,METABOLIC disorders ,CENTRAL nervous system ,THYROID gland function tests - Abstract
Thyroid disorders are clinically characterized by alterations of L-3,5,3’,5’- tetraiodothyronine (T
4 ), L-3,5,3’-triiodothyronine (T3 ), and/or thyroidstimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world’s population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAsproducing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
43. Novel evidence on sepsis-inducing pathogens: from laboratory to bedside.
- Author
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Gatica, Sebastian, Fuentes, Brandon, Rivera-Asín, Elizabeth, Ramírez-Céspedes, Paula, Sepúlveda-Alfaro, Javiera, Catalán, Eduardo A., Bueno, Susan M., Kalergis, Alexis M., Simon, Felipe, Riedel, Claudia A., and Melo-Gonzalez, Felipe
- Subjects
SEPSIS ,PATHOGENIC microorganisms ,STREPTOCOCCUS pyogenes ,PROGNOSIS ,KLEBSIELLA pneumoniae ,SYMPTOMS - Abstract
Sepsis is a life-threatening condition and a significant cause of preventable morbidity and mortality globally. Among the leading causative agents of sepsis are bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, along with fungal pathogens of the Candida species. Here, we focus on evidence from human studies but also include in vitro and in vivo cellular and molecular evidence, exploring how bacterial and fungal pathogens are associated with bloodstream infection and sepsis. This review presents a narrative update on pathogen epidemiology, virulence factors, host factors of susceptibility, mechanisms of immunomodulation, current therapies, antibiotic resistance, and opportunities for diagnosis, prognosis, and therapeutics, through the perspective of bloodstream infection and sepsis. A list of curated novel host and pathogen factors, diagnostic and prognostic markers, and potential therapeutical targets to tackle sepsis from the research laboratory is presented. Further, we discuss the complex nature of sepsis depending on the sepsis-inducing pathogen and host susceptibility, the more common strains associated with severe pathology and how these aspects may impact in the management of the clinical presentation of sepsis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Current and emerging pharmacological treatments for respiratory syncytial virus infection in high-risk infants.
- Author
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Soto, Jorge A., Loaiza, Ricardo A., Echeverría, Sebastián, Ramírez, Robinson A., and Kalergis, Alexis M.
- Abstract
The human respiratory syncytial virus (hRSV) is the leading cause of respiratory infections in children, older adults, and patients with comorbidities. Since the hRSV discovery, multiple efforts have been made to generate therapies that control the devastating effects on the population at risk in winter. This article describes the development of different drugs and treatments approved for use in the risk-population against hRSV infection. In addition, an exhaustive bibliographical review is presented here describing new candidate molecules under evaluation and showing promising results in different assays in animal models and clinical studies. Additionally, we highlight antiviral molecules, monoclonal antibodies, and nanobodies among the new candidate treatments. hRSV is a major burden for the health systems, promoting their collapse worldwide. Therefore, developing new therapies is an essential goal to decrease hospitalization rates caused by hRSV infection in high-risk populations. For this, injecting resources and exploring new targets in addition to the F protein is an interesting alternative to achieve this goal. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
45. Influence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study.
- Author
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Mondaca, Sebastián, Walbaum, Benjamín, Le Corre, Nicole, Ferrés, Marcela, Valdés, Alejandro, Martínez-Valdebenito, Constanza, Ruiz-Tagle, Cinthya, Macanas-Pirard, Patricia, Ross, Patricio, Cisternas, Betzabé, Pérez, Patricia, Cabrera, Olivia, Cerda, Valentina, Ormazábal, Ivana, Barrera, Aldo, Prado, María E., Venegas, María I., Palma, Silvia, Broekhuizen, Richard, and Kalergis, Alexis M.
- Subjects
BOOSTER vaccines ,SARS-CoV-2 ,COVID-19 vaccines ,COVID-19 ,CANCER patients - Abstract
Simple Summary: Cancer patients receiving chemotherapy treatment are at high risk of contracting severe coronavirus disease 2019, which is associated high morbidity and mortality. Recent studies have shown that cancer patients elicit lower humoral and cellular immune responses to both inactivated vaccines and mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. We report the results of assessing the humoral and cellular immune responses induced by the BNT162b2 vaccine booster among cancer patients receiving chemotherapy that had previously completed a primary immunization schedule with either inactivated (CoronaVac) or BNT162b2 SARS-CoV-2 vaccines. Our study demonstrated that booster vaccines elicit strong humoral and cellular responses among cancer patients receiving chemotherapy treatment, regardless of the type of vaccine used as a priming dose. No significant differences in immune response between cancer patients who were given two initial doses of either CoronaVac or BNT162b2 were detected. After adjustment for relevant covariates, the homologous regimen was associated with higher neutralizing antibody positivity and total antibody levels. Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8–12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
46. Gestational Hypothyroxinemia Affects Glutamatergic Synaptic Protein Distribution and Neuronal Plasticity Through Neuron-Astrocyte Interplay
- Author
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Cisternas, Pablo, Louveau, Antoine, Bueno, Susan M., Kalergis, Alexis M., Boudin, Hélène, and Riedel, Claudia A.
- Published
- 2016
- Full Text
- View/download PDF
47. Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells
- Author
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Céspedes, Pablo F., Bueno, Susan M., Ramírez, Bruno A., Gomez, Roberto S., Riquelme, Sebastián A., Palavecino, Christian E., Mackern-Oberti, Juan Pablo, Mora, Jorge E., Depoil, David, Sacristán, Catarina, Cammer, Michael, Creneguy, Alison, Nguyen, Tuan H., Riedel, Claudia A., Dustin, Michael L., and Kalergis, Alexis M.
- Published
- 2014
- Full Text
- View/download PDF
48. Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection.
- Author
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Tognarelli, Eduardo I., Duarte, Luisa F., Farías, Mónica A., Cancino, Felipe A., Corrales, Nicolás, Ibáñez, Francisco J., Riedel, Claudia A., Bueno, Susan M., Kalergis, Alexis M., and González, Pablo A.
- Subjects
DENDRITIC cells ,HUMAN herpesvirus 1 ,REGULATORY T cells ,HEME ,EPITHELIAL cells - Abstract
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host's antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4
+ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
49. New Developments and Challenges in Antibody-Based Therapies for the Respiratory Syncytial Virus.
- Author
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Diethelm-Varela, Benjamín, Soto, Jorge A, Riedel, Claudia A, Bueno, Susan M, and Kalergis, Alexis M
- Subjects
RESPIRATORY syncytial virus ,MONOCLONAL antibodies ,RESPIRATORY therapy ,PALIVIZUMAB ,INDUSTRIAL costs ,VACCINE development - Abstract
Since the discovery of the human respiratory syncytial virus (hRSV), multiple research efforts have been conducted to develop vaccines and treatments capable of reducing the risk of severe disease, hospitalization, long-term sequelae, and death from this pathogen in susceptible populations. In this sense, therapies specifically directed against hRSV are mainly based on monoclonal and polyclonal antibodies such as intravenous IgG (IVIG)-RSV and the monoclonal antibody palivizumab. However, these therapies are associated with significant limitations, including the need for the recruitment of a high number of convalescent volunteers who donate blood to procure IVIG-RSV and the costs associated with the need for repeated administrations of palivizumab. These limitations render this product not cost-effective for populations other than high-risk patients. These problems have underscored that it is still necessary to identify new safe and effective therapies for human use. However, these new therapies must benefit from a comparatively cheap production cost and the opportunity to be available to the high-risk population and anyone who requires treatment. Here, we review the different antibodies used to prevent the pathology caused by hRSV infection, highlighting therapies currently approved for human use and their clinical value. Also, the new, most promising candidates based on preclinical studies and clinical trial results are revised. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
50. Advances in understanding respiratory syncytial virus infection in airway epithelial cells and consequential effects on the immune response
- Author
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Lay, Margarita K., González, Pablo A., León, Miguel A., Céspedes, Pablo F., Bueno, Susan M., Riedel, Claudia A., and Kalergis, Alexis M.
- Published
- 2013
- Full Text
- View/download PDF
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