Intranasal administration of unadjuvanted SARS-CoV-2 spike antigen boosts antigen-specific immune responses induced by parenteral protein subunit vaccine prime in mice and hamsters.

With the continued transmission of SARS-CoV-2 across widely vaccinated populations, it remains important to develop new vaccines and vaccination strategies capable of providing protective immunity and limiting the spread of disease. Heterologous prime-boost vaccination based on the selection of different vaccine formulations and administration routes for priming and booster doses presents a promising strategy for inducing broader immune responses in key systemic and respiratory mucosal compartments. Intranasal vaccination can induce mucosal immune responses at the site of SARS-CoV-2 infection; however, the lack of clinically approved mucosal adjuvants makes it difficult to induce robust immune responses with protein subunit vaccines. Herein, we evaluated the immunogenicity of heterologous prime-boost regimens in mice and hamsters based on a parenteral vaccination of the antigen in combination with sulfated lactosylarchaeol (SLA) archaeosomes, a liposome adjuvant comprised of a single semisynthetic archaeal lipid, followed by an intranasally administered unadjuvanted SARS-CoV-2 spike antigen. Intranasal administration of unadjuvanted spike to mice and hamsters increased serum spike-specific IgG titers and spike-neutralizing activity compared with nonboosted animals. Spike-specific IgA responses were also detected in the bronchoalveolar lavage fluid in the lungs of mice that received an intranasal boost. In hamsters, the intranasal boost showed high efficacy against SARS-CoV-2 infection by protecting from body weight loss and reducing viral titers in the lungs and nasal turbinate. Overall, our heterologous intramuscular prime-intranasal boost with SLA-adjuvanted and unadjuvanted spike, respectively, demonstrated the potential of protein subunit formulations to promote antigen-specific systemic and mucosal immune responses.

Effectiveness of VSV vectored SARS-CoV-2 spike when administered through intranasal, intramuscular or a combination of both.

A critical feature of the VSV vector platform is the ability to pseudotype the virus with different glycoproteins from other viruses, thus altering cellular tropism of the recombinant virus. The route of administration is critical in triggering local and systemic immune response and protection. Most of the vaccine platforms used at the forefront are administered by intramuscular injection. However, it is not known at what level ACE2 is expressed on the surface of skeletal muscle cells, which will have a significant impact on the efficiency of a VSV-SARS-CoV-2 spike vaccine to mount a protective immune response when administered intramuscularly. In this study, we investigate the immunogenicity and efficacy of a prime-boost immunization regimen administered intranasally (IN), intramuscularly (IM), or combinations of the two. We determined that the prime-boost combinations of IM followed by IN immunization (IM + IN) or IN followed by IN immunization (IN + IN) exhibited strong spike-specific IgG, IgA and T cell response in vaccinated K18 knock-in mice. Hamsters vaccinated with two doses of VSV expressing SARS-CoV-2 spike, both delivered by IN or IM + IN, showed strong protection against SARS-CoV-2 variants of concern Alpha and Delta. This protection was also observed in aged hamsters. Our study underscores the highly crucial role immunization routes have with the VSV vector platform to elicit a strong and protective immune response.

Integrated Immunopeptidomics and Proteomics Study of SARS-CoV-2-Infected Calu-3 Cells Reveals Dynamic Changes in Allele-specific HLA Abundance and Antigen Presentation.

We present an integrated immunopeptidomics and proteomics study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to comprehensively decipher the changes in host cells in response to viral infection. Immunopeptidomics analysis identified viral antigens presented by host cells through both class I and class II MHC system for recognition by the adaptive immune system. The host proteome changes were characterized by quantitative proteomics and glycoproteomics and from these data, the activation of toll-like receptor 3-interferon pathway was identified. Glycosylation analysis of human leukocyte antigen (HLA) proteins from the elution and flow-through of immunoprecipitation revealed that SARS-CoV-2 infection changed the glycosylation pattern of certain HLA alleles with different HLA alleles, showing distinct dynamic changes in relative abundance. The difference in the glycosylation and abundance of HLA alleles changed the number of strong binding antigens each allele presented, suggesting the impact of SARS-CoV-2 infection on antigen presentation is allele-specific. These results could be further exploited to explain the imbalanced response from innate and adaptive immune system in coronavirus disease 2019 cases, which would be helpful for the development of therapeutics and vaccine for coronavirus disease 2019 and preparation for future pandemic.

Preclinical evaluation of manufacturable SARS-CoV-2 spike virus-like particles produced in Chinese Hamster Ovary cells.

BACKGROUND: As the COVID-19 pandemic continues to evolve, novel vaccines need to be developed that are readily manufacturable and provide clinical efficacy against emerging SARS-CoV-2 variants. Virus-like particles (VLPs) presenting the spike antigen at their surface offer remarkable benefits over other vaccine antigen formats; however, current SARS-CoV-2 VLP vaccines candidates in clinical development suffer from challenges including low volumetric productivity, poor spike antigen density, expression platform-driven divergent protein glycosylation and complex upstream/downstream processing requirements. Despite their extensive use for therapeutic protein manufacturing and proven ability to produce enveloped VLPs, Chinese Hamster Ovary (CHO) cells are rarely used for the commercial production of VLP-based vaccines. METHODS: Using CHO cells, we aimed to produce VLPs displaying the full-length SARS-CoV-2 spike. Affinity chromatography was used to capture VLPs released in the culture medium from engineered CHO cells expressing spike. The structure, protein content, and glycosylation of spikes in VLPs were characterized by several biochemical and biophysical methods. In vivo, the generation of neutralizing antibodies and protection against SARS-CoV-2 infection was tested in mouse and hamster models. RESULTS: We demonstrate that spike overexpression in CHO cells is sufficient by itself to generate high VLP titers. These VLPs are evocative of the native virus but with at least three-fold higher spike density. In vivo, purified VLPs elicit strong humoral and cellular immunity at nanogram dose levels which grant protection against SARS-CoV-2 infection. CONCLUSIONS: Our results show that CHO cells are amenable to efficient manufacturing of high titers of a potently immunogenic spike protein-based VLP vaccine antigen.

Virus-like particles (VLPs) have a structure that is similar to viruses but they cannot cause infection or illness. If VLPs are injected into the body they produce an immune response similar to that seen following infection by a virus. This means that VLPs can be used as vaccines against viruses that cause illness in people. Many drugs, named biologics, are manufactured using living cells, including cells that were originally derived from Chinese Hamster Ovaries (CHO cells). We developed a simple method to produce VLPs similar to the SARS-CoV-2 virus in CHO cells. We show that vaccination of rodents with these VLPs prevents them from becoming ill following infection with SARS-CoV-2. These VLPs could become a part of an alternative, easily produced vaccine for the prevention of COVID-19 in humans.

Cross protection to SARS-CoV-2 variants in hamsters with naturally-acquired immunity.

Since SARS-CoV-2 was first reported in late 2019, multiple variations of the original virus have emerged. Each variant harbors accumulations of mutations, particularly within the spike glycoprotein, that are associated with increased viral transmissibility and escape immunity. The different mutations in the spike protein of different variants shape the subsequent antibody and T cell responses, such that exposure to different spike proteins can result in reduced or enhanced responses to heterologous variants further down the line. Globally, people have been exposed and re-exposed to multiple variations of the Ancestral strain, including the five variants of concerns. Studies have shown that the protective immune response of an individual is influenced by which strain or combination of strains they are exposed to. The initial exposure to a specific strain may also shape their subsequent immune patterns and response to later infections with a heterologous virus. Most immunological observations were carried out early during the pandemic when the Ancestral strain was circulating. However, SARS-CoV-2 variants exhibit varying patterns of disease severity, waning immunity, immune evasion and sensitivity to therapeutics. Here we investigated the cross-protection in hamsters previously infected with a variant of concern (VOC) and subsequently re-infected with a heterologous variant. We also determined if cross-protection and immunity were dependent on the specific virus to which the hamster was first exposed. We further profiled the host cytokine response induced by each SARS-CoV-2 variants as well as subsequent to re-infection. A comparative analysis of the three VOCs revealed that Alpha variant was the most pathogenic VOC to emerge. We showed that naturally acquired immunity protected hamsters from subsequent re-infection with heterologous SARS-CoV-2 variant, regardless which variant the animal was first exposed to. Our study supports observations that heterologous infection of different SARS-CoV-2 variants do not exacerbate disease in subsequent re-infections. The continual emergence of new SARS-CoV-2 variants mandates a better understanding of cross-protection and immune imprinting in infected individuals. Such information is essential to guide vaccine strategy and public policy to emerging SARS-CoV-2 VOCs and future novel pandemic coronaviruses.

Arsenal of nanobodies shows broad-spectrum neutralization against SARS-CoV-2 variants of concern in vitro and in vivo in hamster models.

Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The nanobodies were collectively shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across existing VoCs; wide-ranging epitopic and mechanistic diversity and high and broad in vitro neutralization potencies. A select set of Fc-fused nanobodies showed high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. In vivo protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a potential therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to combat multiple SARS-CoV-2 variants.

Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters.

With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.

Immunogenic and efficacious SARS-CoV-2 vaccine based on resistin-trimerized spike antigen SmT1 and SLA archaeosome adjuvant.

The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.

Evaluation of the systemic alterations triggers by Porthidium lansbergii lansbergii snake venom.

The systemic effects generated by Porthidium lansbergii lansbergii envenoming, a species found in the northern region of Colombia, is poorly known. The present study aimed to analyze for the first time the mice's behavior, the histological alterations, and changes in biochemical markers levels resulting from the intraperitoneal injection of an LD50 of P. lansbergii lansbergii snake venom on mice. The envenoming mice displayed hypodynamic condition, clonic head movements, accompanied by bradypnea and thoracoabdominal imbalance. After 7 h of envenoming, the mice showed an ecchymotic region at the injection site, including bleeding in the pleural, liver, and kidney capsules. The effect on the brain revealed a micro-hemorrhage in the sensorimotor cortex with substantial loss of neurons. The venom caused dilated blood vessels in lung tissue, with endothelial necrosis associated with alveolar rupture. The liver showed parenchyma alteration with many extravasated erythrocytes. The kidneys exhibited renal tubules necrosis and a statistically significant increase in creatinine concentration. ALP and ALT's enzymatic activities remained constant at 7 h after envenoming but increased at 12 h. AST and LDH were significantly increased at 7 h but decreased to the near baseline 12 h after venom administration. Massive hemorrhages could trigger a hypovolemic shock, which could lead to death after several h without treatment. Knowledge of P. lansbergii lansbergii snake bites' injuries is essential to make the appropriate diagnostic in human envenoming cases by this snake.

DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model.

SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

Formación en salud mental en psicología, trabajo social, medicina, enfermería y terapia ocupacional en Colombia / Training in mental health in psychology, social work, medicine, nursing and occupational therapy in colombia / Formação em saúde mental em psicología, trabalho social, medicina, enfermagem e terapia ocupacional na Colômbia

Este artículo presenta los resultados de una investigación que tuvo como objetivo analizar el componente de salud mental presente en las mallas curriculares de los programas universitarios de psicología, trabajo social, medicina, enfermería y terapia ocupacional en Colombia, 2015. Se trata de un estudio cualitativo descriptivo, para el cual se hizo uso de fuentes documentales, como las mallas curriculares de los programas y la información descriptiva de los mismos ofrecidas en sus páginas web, y de un grupo de discusión con representantes de las disciplinas en cuestión; participaron 321 programas universitarios que para 2015 se encontraban activos en el Sistema Nacional de Información de la Educación Superior. Se encuentra que la formación en salud mental no es tema de interés explícito en los planes de formación curricular, constituyéndose por lo tanto en un contenido abordado dentro de otros temas más generales, lo que permite concluir que los retos para la formación en salud mental que se infieren de la ley colombiana de salud mental, no son acogidos suficientemente.

This article presents the results of a research that aimed at analyzing the mental health component present in the curriculum of the Psychology, Social Work, Medicine, Nursing and Occupational Therapy university programs in Colombia, in 2015. It is a descriptive qualitative study, for which documentary sources were used such as the curriculum of the programs and the descriptive information offered on their web pages, and a discussion group with representatives of the disciplines in question. A total of 321 university programs that by 2015 were active in the National Information System of Higher Education participated in the study. It was found that training in mental health is not a topic of explicit interest in curricular training plans, thus constituting a content addressed within other more general topics, which allows concluding that the challenges for training in mental health inferred from the Colombian Mental Health Law, are not sufficiently spread.

Este artigo apresenta os resultados duma pesquisa que teve como objetivo analisar o componente de saúde mental presente nas matrizes curriculares dos programas universitários de psicologia, trabalho social, medicina, enfermagem e terapia ocupacional na Colômbia, 2015. Trata-se dum estudo qualitativo descritivo, para o qual se fez uso de fontes documentais, como as matrizes curriculares dos programas e a informação descritiva das mesmas oferecidas em suas páginas web, e dum grupo de discussão com representantes das disciplinas em questão; participaram 321 programas universitários que para 2015 se encontravam ativos no Sistema Nacional de Informação da Educação Superior. Encontra-se que a formação em saúde mental não é tema de interesse explícito nos planos de formação curricular, constituindo-se portanto em um conteúdo abordado dentro de outros temas mais gerais, o que permite concluir que os retos para a formação em saúde mental que se inferem da lei colombiana de saúde mental, não são aceitados suficientemente.

Formación en salud mental en psicología, trabajo social, medicina, enfermería y terapia ocupacional en Colombia / Training in mental health in psychology, social work, medicine, nursing and occupational therapy in Colombia / Formação em saúde mental em psicología, trabalho social, medicina, enfermagem e terapia ocupacional na Colômbia

Resumen Este artículo presenta los resultados de una investigación que tuvo como objetivo analizar el componente de salud mental presente en las mallas curriculares de los programas universitarios de psicología, trabajo social, medicina, enfermería y terapia ocupacional en Colombia, 2015. Se trata de un estudio cualitativo descriptivo, para el cual se hizo uso de fuentes documentales, como las mallas curriculares de los programas y la información descriptiva de los mismos ofrecidas en sus páginas web, y de un grupo de discusión con representantes de las disciplinas en cuestión; participaron 321 programas universitarios que para 2015 se encontraban activos en el Sistema Nacional de Información de la Educación Superior. Se encuentra que la formación en salud mental no es tema de interés explícito en los planes de formación curricular, constituyéndose por lo tanto en un contenido abordado dentro de otros temas más generales, lo que permite concluir que los retos para la formación en salud mental que se infieren de la ley colombiana de salud mental, no son acogidos suficientemente.

Abstract This article presents the results of a research that aimed at analyzing the mental health component present in the curriculum of the Psychology, Social Work, Medicine, Nursing and Occupational Therapy university programs in Colombia, in 2015. It is a descriptive qualitative study, for which documentary sources were used such as the curriculum of the programs and the descriptive information offered on their web pages, and a discussion group with representatives of the disciplines in question. A total of 321 university programs that by 2015 were active in the National Information System of Higher Education participated in the study. It was found that training in mental health is not a topic of explicit interest in curricular training plans, thus constituting a content addressed within other more general topics, which allows concluding that the challenges for training in mental health inferred from the Colombian Mental Health Law, are not sufficiently spread.

Resumo Este artigo apresenta os resultados duma pesquisa que teve como objetivo analisar o componente de saúde mental presente nas matrizes curriculares dos programas universitários de psicologia, trabalho social, medicina, enfermagem e terapia ocupacional na Colômbia, 2015. Trata-se dum estudo qualitativo descritivo, para o qual se fez uso de fontes documentais, como as matrizes curriculares dos programas e a informação descritiva das mesmas oferecidas em suas páginas web, e dum grupo de discussão com representantes das disciplinas em questão; participaram 321 programas universitários que para 2015 se encontravam ativos no Sistema Nacional de Informação da Educação Superior. Encontra-se que a formação em saúde mental não é tema de interesse explícito nos planos de formação curricular, constituindo-se portanto em um conteúdo abordado dentro de outros temas mais gerais, o que permite concluir que os retos para a formação em saúde mental que se inferem da lei colombiana de saúde mental, não são aceitados suficientemente.

Transdisciplinariedad en salud mental: Una propuesta de modelo de formación / Transdisciplinarity in mental health: A proposal of training model

Este artículo presenta los resultados de una investigación que tuvo como objetivo diseñar una propuesta de Modelo de Formación Transdisciplinar en Salud Mental para cuatro programas universitarios en la región de Antioquia (Colombia), con el propósito de contribuir al mejoramiento de esta formación en los profesionales de Psicología, Enfermería, Trabajo Social y Medicina. El estudio tuvo un enfoque cualitativo de tipo documental, aplicado y hermenéutico, que propició la participación de formadores, empleadores y profesionales de las nueve subregiones de Antioquia. Como estrategias de recolección de información, se realizó revisión documental y entrevistas semiestructuradas; se hizo análisis categorial a través de Nvivo, y finalmente se realizó un ejercicio de validación por medio de mesas de trabajo con informantes de la investigación. El desarrollo de la investigación permitió que los informantes pudieran dar cuenta de los principales eventos en salud mental de sus contextos, las necesidades de formación del recurso humano que los acompaña y de algunas estrategias para la formación profesional de este talento humano. Igualmente, se identificaron y describieron los principales eventos en salud mental que son reportados en medios oficiales del Departamento de Antioquia. En conclusión, se da lugar a la construcción del documento que presenta la Propuesta de Modelo de Formación Transdisciplinar en Salud Mental para cuatro programas de pregrado en Antioquia, que incluye modalidades de aplicación que bien pueden acogerse por los diferentes programas en su formación curricular y/o complementaria.

This article presents the results of a research that aimed to design a proposal of a Transdisciplinary Training Model for Mental Health (MH) for 4 Undergraduate Programs in the department (state) of Antioquia (Colombia), with the purpose of contributing to the improvement of the training for the professionals of Psychology, Nursing, Social Work and Medicine. The study had a qualitative approach of an applied, hermeneutic and documenting type, whose data collection strategies consisted of documentary review and semi-structured interviews. Under the first strategy the disciplinary objects of Psychology, Nursing, Social Work and Medicine were reviewed, which allowed the description of the objects of each discipline, the identification of points of convergence and therefore of the interdisciplinary and transdisciplinary possibilities. Likewise, we proceeded with the reading of some reports provided by government entities, responsible for ensuring the health and mental health of the inhabitants of Antioquia, to recognize the main events in MH reported in the state. After the documentary review, semi-structured interviews were conducted with different actors involved with the MH: trainers, employers and professionals from the nine subregions of Antioquia; therefore, there were three different interview scripts. Once the interviews were conducted, they were subjected to a categorical analysis through Nvivo. Finally, in a public event with the participants of the research a validation exercise of The Training Model Proposal was carried out, there the results obtained at that point were socialized, so that it was debated in small groups and feedbacks were given. These feedbacks were considered for the final formulation of the Transdisciplinary Training Model Proposal. The development of the research allowed the Interviewed people to account for the more significant mental health events in their areas, as well as the training needs of the human resource that go along with these events and, some strategies for the professional training of this human talent. Likewise, the more significant events in mental health that are reported in official media of the Department of Antioquia were identified and described. Based on these results, the conceptualization of MH was considered for the Thematic Component of the Proposal, training in the clinical area, which in turn implies training in psychopathology, psychiatric patient care and intervention strategies; courses oriented to the understanding and intervention of violence, consumption of Psychoactive Substances, family MH and community MH; knowledge in mental health care procedures, primary care in MH and different approaches to care in MH, such as psychosocial, social determinants of MH and differential approaches, especially the life cycle in relation to childhood and adolescence; Emphasis is also placed on the importance of training in public policies, public health and the functioning of the General Social Security and Health System. It takes place the creation of the document that presents the Proposal for a Model of Transdisciplinary Training in Mental Health for 4 Undergraduate Programs in Antioquia; this proposal includes modalities of application that can be accepted by the different programs in their curricular and/or complementary training. The curricular training, whose topics are stated in the results, must be accompanied by the strengthening of competencies associated with the ability to read contextualized MH issues, which contribute to interventions closer to the reality of the population; as well as, to attend to aspects related to the student's being, oriented to an ethical reflection, to the MH of the student and to the strengthening of their vocation.

Doble aneuploidía en un niño colombiano: síndrome de Down-Klinefelter, con fenotipo de síndrome de Down / Double aneuploidy in a Colombian child: Down-Klinefelter syndrome with Down syndrome phenotype

La ocurrencia de una doble aneuploidía en una misma persona es un evento relativamente raro. Se presenta el caso de un niño de siete meses de edad, de padres no consanguíneos con características clínicas de síndrome de Down y cariotipo 48XXY.

The occurrence of double aneuploidy in one person is a relatively rare phenomenon. We report the case of a 7-month-old child, the third-born of non-consanguineous parents, with clinical features of Down syndrome and karyotype 48XXY.

Conjuntivitis alérgica / Allergic conjunctivitis

Se presenta una revisión de ''Conjuntivitis Alérgica" haciendo un repaso inicial de la anatomía funcional de la conjuntiva, definición de términos, revisando los signos y síntomas principales para estudiar finalmente cada tipo de conjuntivitis alérgica en forma independiente, los mecanismos inmunológicos y las posibilidades terapéuticas existentes.