Eye and lid involvement as an uncommon feature of pemphigus foliaceus in a pediatric patient.

Pemphigus foliaceus (PF) is an autoimmune blistering disorder which affects the superficial layers of the epidermis with rare mucosal involvement. We present the case of a 12-year-old girl with PF involving the eyes and eyelids. A literature review of pediatric nonendemic PF revealed another two cases with ocular manifestations. Eyelid involvement is an uncommon feature of PF that should be properly identified and treated.

ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas' disease.

Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.

Biofortification of Kidney Bean (Phaseolus vulgaris L.) Crops Applying Zinc Sulfate and Ferric Sulfate: Pilot Crop in Colombia.

Agriculture is one of the economic activities with the most potential in Colombia, given its climatic and geographical conditions. Bean cultivation is classified as climbing, which grows in a branched way, and bushy, whose growth occurs up to 70 cm. The objective of this research was to study zinc and iron sulfates in different concentrations as fertilizers capable of increasing the nutritional value of kidney beans (Phaseolus vulgaris L.), whose strategy is known as biofortification, and thus determine the most effective sulfate. The methodology details the sulfate formulations, their preparation, the application of additives, sampling and quantification methods of total iron, total zinc, °Brix, carotenoids, chlorophylls a, b, and antioxidant capacity using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method in leaves and pods. As for the results, it was found that biofortification with iron sulfate and zinc sulfate is a strategy that favors the country's economy and human health, because it allows the increase of minerals, antioxidant capacity and total soluble solids.

Association of rs4711998 of IL-17A, rs2275913 of IL-17A and rs763780 IL-17F gene polymorphisms with non-segmental vitiligo in a Mexican population.

Vitiligo is the most common depigmenting disease characterized by achromic macules due to selective loss of melanocytes. The pathogenesis remains poorly elucidated, and multiple hypotheses exist regarding its pathogenesis. Evidence suggests that stress on melanocytes can result in activation of the immune system, and involvement of both activated cluster of differentiation (CD8+) cytotoxic and CD4+ T cells in the dysfunction, depigmentation, and apoptosis of melanocytes. Recent studies show that the interleukin 17 (IL-17) axis plays a central role in the pathogenesis of the disease. IL-17 is an important regulatory effector cytokine in this pathway. The aim of this study was to evaluate the association of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) with vitiligo in a Northeastern Mexican population. This was a case-control study and included 116 patients with vitiligo and 116 control subjects. Genotype characterization of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A p ≤ 0.05 was considered significant. It was observed that the combination of the genotypes GG/GA for IL-17F rs763780 (7488A/G) was associated with an increased risk for the development of vitiligo (OR 2.0943, 95% Cl 1.2375-3.5445, p = 0.0056). Regarding IL-17A rs4711998 (-832A/G) and IL-17A rs2275913 (-197G/A) genotyping, no association with vitiligo development was found. In conclusion, the SNP rs763780 in the IL-17F gene appears to be a risk factor for vitiligo development in this Mexican population and it may be useful in future studies, especially for the development of new therapies.

Association between the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants with vitiligo: study on a Mexican population

Abstract Background: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. Objective: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. Methods: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. Results: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). Conclusion: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.

Association between the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants with vitiligo: study on a Mexican population.

BACKGROUND: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. OBJECTIVE: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. METHODS: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. RESULTS: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). CONCLUSION: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.

Development and validation of an enzyme-linked immunoassay kit for diagnosis and surveillance of COVID-19.

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-CoV-2 antibodies in human sera with high reliability.

DEVELOPMENT AND VALIDATION OF AN ENZYME-LINKED IMMUNOASSAY KIT FOR DIAGNOSIS AND SURVEILLANCE OF COVID-19.

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-CoV-2 antibodies in human sera with high reliability.

Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein.

Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4+ and CD8+ T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.

The C-Terminal Domain of Staphylococcus aureus Zinc Transport Protein AdcA Binds Plasminogen and Factor H In Vitro.

Bacterial acquisition of metals from a host is an essential attribute to facilitate survival and colonization within an infected organism. Staphylococcus aureus, a bacterial pathogen of medical importance, has evolved its strategies to acquire multiple metals, including iron, manganese, and zinc. Other important strategies for the colonization and infection of the host have been reported for staphylococci and include the expression of adhesins on the bacterial surface, as well as the acquisition of host plasminogen and complement regulatory proteins. Here we assess the ability of the zinc transport protein AdcA from Staphylococcus aureus, first characterized elsewhere as a zinc-binding protein of the ABC (ATP-binding cassette) transporters, to bind to host molecules. Like other staphylococcus ion-scavenging proteins, such as MntC, a manganese-binding protein, AdcA interacts with human plasminogen. Once activated, plasmin bound to AdcA cleaves fibrinogen and vitronectin. In addition, AdcA interacts with the human negative complement regulator factor H (FH). Plasminogen and FH have been shown to bind to distinct sites on the AdcA C-terminal portion. In conclusion, our in vitro data pave the way for future studies addressing the relevance of AdcA interactions with host molecules in vivo.

The C-terminal domain of Staphylococcus aureus zinc transport protein AdcA binds plasminogen and factor H in Vitro

Bacterial acquisition of metals from a host is an essential attribute to facilitate survival and colonization within an infected organism. Staphylococcus aureus, a bacterial pathogen of medical importance, has evolved its strategies to acquire multiple metals, including iron, manganese, and zinc. Other important strategies for the colonization and infection of the host have been reported for staphylococci and include the expression of adhesins on the bacterial surface, as well as the acquisition of host plasminogen and complement regulatory proteins. Here we assess the ability of the zinc transport protein AdcA from Staphylococcus aureus, first characterized elsewhere as a zinc-binding protein of the ABC (ATP-binding cassette) transporters, to bind to host molecules. Like other staphylococcus ion-scavenging proteins, such as MntC, a manganese-binding protein, AdcA interacts with human plasminogen. Once activated, plasmin bound to AdcA cleaves fibrinogen and vitronectin. In addition, AdcA interacts with the human negative complement regulator factor H (FH). Plasminogen and FH have been shown to bind to distinct sites on the AdcA C-terminal portion. In conclusion, our in vitro data pave the way for future studies addressing the relevance of AdcA interactions with host molecules in vivo.

Updates and new medical treatments for vitiligo (Review).

Vitiligo is a multifactorial disease characterized by the loss of skin pigment, which results in achromic macules and patches. There are currently several medical treatments available, which aim to arrest progression and induce skin repigmentation. These treatments alone or combined have exhibited varying degrees of pigmentation, and the majority are safe and effective. All therapies for vitiligo are limited, and no known treatment can consistently produce repigmentation in all patients. Individualized treatment is appropriate according to the location, clinical presentation and the presence of disease activity. The present review summarizes the medical treatments available for vitiligo: Systemic and topic pharmacological therapies, physical and depigmentation treatments. Several treatments are still underway and have not yet been approved. However, due to the promising preliminary results, these are also mentioned in the present review.

Alteraciones musculoesqueléticas y adaptaciones biomecánicas durante los trimestres de embarazo: una revisión sistemática / Musculoskeletal changes and biomechanic adaptations during the three trimesters of pregnancy: a sistematic review

Resumen Quesada Salazar, N. (2021). Alteraciones musculoesqueléticas y adaptaciones biomecánicas durante los trimestres de embarazo: una revisión sistemática. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(1), 1-27. El embarazo es un proceso progresivo que involucra cambios de tipo hormonal, mecánico, fisiológico y emocional en la mujer y que causa que el sistema musculoesquelético se adapte constantemente. Estos cambios suelen identificarse a través de la postura y la biomecánica de los movimientos en la vida diaria. En esta investigación, se realizó una revisión sistemática para encontrar las principales alteraciones y adaptaciones durante el embarazo, incluyendo artículos del 2008 al 2018, con mujeres gestantes sanas, con un solo feto, sin alteraciones musculoesqueléticas previas, de Índice de Masa Corporal (IMC) normal y cualquier metodología de investigación excepto estudios de caso. Se identificaron 13 estudios que refieren evaluar las tres etapas de gestación, edades desde los 20 a los 35 años, así como con diversos objetivos de investigación. La postura de la mujer gestante presenta un aumento de la lordosis lumbar, la curvatura torácica y el ángulo de inclinación anterior de la pelvis. La tarea de sentarse y levantarse de una silla requiere de mayor control del movimiento, así como de tiempo de ejecución. La oscilación y las fuerzas de reacción del suelo del Centro de Presión corporal aumentan al estar de pie, lo que resulta en una mayor distancia entre los pies, como estrategia de control del equilibrio. Finalmente, la biomecánica de la marcha se adapta a una menor velocidad, longitud de paso y etapa de despegue de los pies del piso, con un aumento del ancho de paso y una mayor base de apoyo. En la gestación, la mujer desarrolla adaptaciones de tipo anatómicas y mecánicas como respuesta a los cambios progresivos experimentados.

Abstract Quesada Salazar, N. (2021). Musculoskeletal changes and biomechanic adaptations during the three trimesters of pregnancy: a sistematic review. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(1), 1-27. Pregnancy is a progressive process involving hormonal, mechanical, physiological, and emotional changes in women that stimulates the musculoskeletal system to adapt constantly. These changes are usually identified through posture and the biomechanics of day-to-day movements. This study consists of a systematic review of the main alterations and adaptations during pregnancy, including articles from 2008 to 2018 that involved healthy pregnant women without previous musculoskeletal affections, with a single fetus and normal BMI, and any methods of study excluding case studies. Thirteen studies were identified which indicate evaluation of participants ages from 20 to 35 years during their three trimesters of pregnancy, as well as different study objectives. Posture in a pregnant woman shows an increase in the lumbar lordosis, thoracic curvature, and anterior tilt of the pelvis. The task of sitting and rising from a chair requires more control to complete the movement as well as increased execution time. Oscillation movement and ground reaction forces of the center of pressure of the body increase during standing posture, which results in a greater distance between the feet as a strategy to control the balance. Finally, gait biomechanics adapt to a slower speed, smaller step length, and less time with feet off the ground, but a wider step and support base. During pregnancy, women develop anatomic and mechanic adaptations in response to the progressive changes they experience.

Resumo Quesada Salazar, N. (2021). Alterações musculoesqueléticas e adaptações biomecânicas durante os trimestres de gravidez: uma revisão sistemática. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(1), 1-27. A gravidez é um processo progressivo que envolve mudanças de tipo hormonal, mecânico, fisiológico e emocional na mulher e que faz com que o sistema musculoesquelético se adapte constantemente. Essas mudanças tendem a ser identificadas por meio da postura e a biomecânica dos movimentos na vida diária. Nesta pesquisa foi realizada uma revisão sistemática para encontrar as principais alterações e adaptações durante a gravidez, incluindo artigos de 2008 a 2018, com mulheres gestantes saudáveis, com um único feto, sem alterações musculoesqueléticas prévias, com Índice de Massa Corporal (IMC) normal e qualquer metodologia de pesquisa, exceto estudos de caso. Foram identificados 13 estudos que registram avaliar as três etapas de gestação, com idades desde os 20 aos 35 anos, igualmente com diversos objetivos de pesquisa. A postura da mulher gestante apresenta um aumento de lordose lombar, curvatura toráxica e ângulo de inclinação anterior da pelve. A tarefa de sentar-se e levantar-se de uma cadeira exige maior controle do movimento, assim como de tempo de execução. A oscilação e as forças de reação do solo do Centro de Pressão corporal aumentam ao estar de pé, resultando em uma maior distância entre os pés, como estratégia de controle do equilíbrio. Finalmente, a biomecânica da marcha se adapta a uma menor velocidade, longitude de passo e fase de retirada dos pés do chão, com um aumento da largura do passo e uma maior base de apoio. Na gestação, a mulher desenvolve adaptações de tipo anatômicas e mecânicas como resposta para mudanças progressivas experimentadas.

Cutaneous Manifestations of Castleman Disease: Histopathological Characteristics and Review of Literature.

ABSTRACT: Castleman disease (CD) is a poorly understood lymphoproliferative disorder characterized by enlarged lymph nodes. The spectrum of differential diagnoses is wide, and it is hard to differentiate from other diseases. Cutaneous involvement of CD is rare, and studies that describe cutaneous dermatopathology of CD are scarce. The aim of this study was to collect case reports of CD with cutaneous manifestations and identify potential relevant histopathological features. We found that cases of CD with cutaneous manifestations often exhibited dermal lymphoid follicles with follicle center infiltration of lymphocytes and plasma cells. These dermal follicles also had regressive or atrophic germinal centers and were penetrated by hyalinized vessels. Patients with CD also consistently exhibited perivascular and deep dermal inflammatory infiltrate, primarily composed of lymphocytes and plasma cells. We intend to raise awareness of this rare entity and provide more histopathological information regarding its dermatological manifestations.

A Previously Healthy 18-Year-Old Male With Fever, Arrhythmia, and Shock.

A male individual aged 18 years with no significant past medical history presented with fever, headache, dry cough, and chest pain. On clinical examination, he had tachycardia and hypotension needing intravenous fluid resuscitation and inotropic support. A chest radiograph revealed streaky lung opacities, and he was treated with antibiotics for suspected community-acquired pneumonia complicated by septic shock. Significant elevation of cardiac enzymes was noted, and there was a continued need for inotropes to maintain normotension. He also developed intermittent bradycardia, with serial electrocardiograms showing first-degree atrioventricular block, low-voltage QRS complexes, and ST-T wave changes and telemetry demonstrating junctional and ventricular escape rhythm. A complete workup for sepsis and acute myocarditis were performed to find the etiologic agent. Intravenous immunoglobulins were started to treat myocarditis, with eventual clinical improvement. He was eventually diagnosed with an unusual etiology for his illness. He was noted to still have intermittent ventricular escape rhythm on electrocardiograms on follow-up 2 weeks after discharge but continues to remain asymptomatic and in good health.

Novel immunological and genetic factors associated with vitiligo: A review.

Vitiligo is a skin disorder characterized by depigmentation of the skin due to a lack of melanin. This condition affects men and woman of all ages and its incidence is not restricted by ethnicity or region. Vitiligo is a multifactorial disease, in which melanocytes, which serve important functions in skin pigmentation and immune processes, are impaired. There is sufficient evidence that immunological and genetic factors are primarily responsible for the destruction and dysfunction of melanocytes. Therefore, genetic DNA sequence variants that participate in skin homeostasis, pigmentation and immune response regulation, as well as altered expression patterns, may contribute to the risk of developing vitiligo. The current review presented an overview of the mechanism of pigmentation and of currently known factors involved in depigmentation, as well as the classification, epidemiology, associated comorbidities, risk factors, immunopathogenesis and several genetic and molecular changes associated with vitiligo.