Normal values of the fronto-occipital relationship in fetuses between 18 and 40 weeks at two maternal fetal medicine units: Bogotá, Colombia.

OBJECTIVE: To establish nomograms for linear measurements of the frontal and occipital horns of the lateral ventricle and their relationship, in pregnant patients between 18 and 40 weeks of gestation and having attended 2 units of Maternal Fetal Medicine in Bogotá-Colombia. METHODOLOGY: A descriptive cross-sectional study with an analytical component was carried out on pregnant patients who utilized the ultrasound services at 2 Maternal-Fetal Medicine units in Bogotá, between 18 and 40 weeks of pregnancy who underwent measurement. From the anterior and posterior horns of the lateral ventricles, the fronto-occipital ratio was calculated at each gestational week, and nomograms were created for each of these variables. RESULTS: Nine hundred and seventy-eight patients were included in the study. The distance of the frontal horns ranged between 6.9 and 51.6 mm with a mean of 19.1 ± 5.8 mm; that of the occipital horns had a measurement between 8.7 and 53 mm with a mean of 28, 1 ± 8.9 mm; on the other hand, the fronto-occipital ratio (FOR) yielded a mean of 0.365 ± 0.067 (0.136-0.616) without bearing any relation to gestational age. The trend of normal values for the studied population is displayed, plotted in percentile curves and nomograms for each gestational age. CONCLUSION: The measurement of the frontal and occipital horns, and the calculation of the fronto-occipital relationship is technically possible between 18 and 40 weeks, finding that the anterior and posterior horns have a positive linear relationship with gestational age. Contrarily, the FOR does not correlate with the gestational age, it was possible to establish a table of percentiles that allows determining the normal values for these measurements during pregnancy.

B cell-targeted polylactic acid nanoparticles as platform for encapsulating jakinibs: potential therapeutic strategy for systemic lupus erythematosus.

Background: B cells are pivotal in systemic lupus erythematosus and autoimmune disease pathogenesis. Materials & methods: To address this, Nile Red-labeled polylactic acid nanoparticles (NR-PLA NPs) loaded with the JAK inhibitor baricitinib (BARI), specifically targeting JAK1 and JAK2 in B cells, were developed. Results: Physicochemical characterization confirmed NP stability over 30 days. NR-PLA NPs were selectively bound and internalized by CD19+ B cells, sparing other leukocytes. In contrast to NR-PLA NPs, BARI-NR-PLA NPs significantly dampened B-cell activation, proliferation and plasma cell differentiation in healthy controls. They also inhibited key cytokine production. These effects often surpassed those of equimolar-free BARI. Conclusion: This study underscores the potential of PLA NPs to regulate autoreactive B cells, offering a novel therapeutic avenue for autoimmune diseases.

In this study, a new approach to treating autoimmune diseases, particularly systemic lupus erythematosus, was investigated by focusing on a type of immune cell called B cells. Special nanoparticles (NPs) labeled with Nile Red (NR) and made from polylactic acid (PLA) were created. These NPs were loaded with a drug called baricitinib (BARI), which targets specific proteins (JAK1 and JAK2) in B cells. This was done to determine if these NPs could help control the behavior of B cells, which are important in autoimmune diseases. First, these NPs remained stable for a long time (30 days). The NR-labeled PLA NPs (NR-PLA NPs) were also good at attaching to and entering a specific type of B cell called CD19⁺ B cells while leaving other types of immune cells alone. The use of NR-PLA NPs loaded with BARI produced exciting results. These NPs were better at reducing the activity, growth and transformation of B cells into plasma cells compared with the drug BARI by itself. They also stopped the production of certain immune system signals called cytokines, which are usually overactive in autoimmune diseases. This work suggests that PLA NPs could be a promising way to control overactive B cells that contribute to autoimmune diseases like systemic lupus erythematosus. This could open a new and exciting path for developing treatments for these conditions.

Embarazo postmanga gástrica en pacientes con irregularidades menstruales / Pregnancy after gastric sleeve in patients with menstrual irregularities

Resumen OBJETIVO: Estimar la cantidad de pacientes con irregularidades menstruales que se embarazaron luego de una cirugía bariátrica (manga gástrica) y describir los desenlaces de los embarazos. MATERIALES Y MÉTODOS: Estudio retrospectivo de serie de casos de pacientes obesas y con irregularidades menstruales intervenidas mediante cirugía bariátrica (manga gástrica). Se operaron entre el 1 de junio de 2014 y el 31 de diciembre de 2019 en el Centro Médico Imbanaco Cali, Colombia. RESULTADOS: De 1418 cirugías bariátricas, tipo manga gástrica, 117 pacientes cumplieron con los criterios de inclusión, 80 de ellas se localizaron telefónicamente y aceptaron incluirse al estudio. Luego de la manga gástrica, el 86.25% (n = 69) de las pacientes logró la regularización de sus ciclos menstruales. Además, el 31% (n = 25) consiguió el embarazo, 80% (n = 20) de ellas tenían la intención de buscar el embarazo. Los desenlaces de esos embarazos fueron favorables, con partos a término, con adecuado peso y talla al nacer. CONCLUSIONES: Después de la cirugía bariátrica, tipo manga gástrica, en mujeres con irregularidades menstruales, 25 de las 80 pacientes se embarazaron y los desenlaces obstétricos fueron satisfactorios. Sin duda, hacen falta más estudios prospectivos para poder afirmar, con una mejor representación estadística, las repercusiones de la disminución del peso corporal en la tasa de fertilidad.

Abstract OBJECTIVE: To estimate the number of patients with menstrual irregularities who became pregnant after bariatric surgery (gastric sleeve) and to describe the pregnancy outcomes. MATERIALS AND METHODS: Retrospective study of a series of cases of obese patients with menstrual irregularities who underwent bariatric surgery (gastric sleeve). They were operated between June 1, 2014 and December 31, 2019 at the Imbanaco Cali Medical Center, Colombia. RESULTS: Of 1418 bariatric surgeries, gastric sleeve type, 117 patients met the inclusion criteria, 80 of them were located by telephone and agreed to be included in the study. After gastric sleeve, 86.25% (n = 69) of the patients achieved regularization of their menstrual cycles. In addition, 31% (n = 25) achieved pregnancy, 80% (n = 20) of them intended to seek pregnancy. The outcomes of these pregnancies were favorable, with full-term deliveries, with adequate weight and height at birth. CONCLUSIONS: After bariatric surgery, gastric sleeve type, in women with menstrual irregularities, 25 of the 80 patients became pregnant and the obstetric outcomes were satisfactory. Undoubtedly, more prospective studies are needed to be able to affirm, with a better statistical representation, the repercussions of the decrease in body weight on the fertility rate.

Modulation of B cell activation by extracellular vesicles and potential alteration of this pathway in patients with rheumatoid arthritis.

BACKGROUND: Extracellular vesicles are involved in the intercellular communication of the immune system. In rheumatoid arthritis (RA), these structures are considered a source of autoantigens that drive proinflammatory responses of innate immune cells. A high concentration of circulating medium/large size extracellular vesicles (m/lEVs) and m/lEVs forming immune complexes (m/lEV-ICs) have been associated with disease activity and systemic inflammation in patients with RA. B cells are central components of RA immunopathology because of their involvement in the production of autoantibodies, antigen presentation, and cytokine production. However, the effect of m/lEVs on B cell function in the context of RA and other autoimmune diseases remains unknown. METHODS: We evaluated the effect of m/lEVs obtained from healthy donors (HD) and patients with RA on B cell responses in vitro. In addition, we evaluated the effect of pre-exposition of monocyte-derived macrophages (MDM) to m/lEVs on activation of autologous B cells from HD and patients. RESULTS: The presence of m/lEVs reduced the frequency of CD69+ and CD86+ B cells from HD activated by an agonist of antigen receptor. This regulation of the B cell activation markers by m/lEVs was partially dependent on phosphatidylserine binging. These m/lEVs also reduced the proliferation, calcium mobilization, and global phosphorylation of tyrosine. Similar responses were observed in B cells from patients with RA. However, the presence of m/lEVs promoted high antibody levels in B cells cultured with T cell-dependent stimuli by 7 days. In addition, despite the direct inhibitory effect of m/lEVs on early B cell responses, when B cells were cocultured with autologous MDM previously exposed to m/lEVs or m/lEV-ICs, an increased frequency of CD69+ B cells from patients with RA was observed, albeit not with cells from HD. CONCLUSIONS: These data together suggest that m/lEVs have a direct modulatory effect in early responses of B cells through B cell receptor that can potentially fail in patients with RA because of the impact of these vesicles over cells of the innate immune system. This phenomenon can potentially contribute to the loss of tolerance and disease activity in patients with RA.

Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals.

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant recipients (KTXs). We found that, unlike healthy subjects, KTXs presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cell, SARS-CoV-2 receptor binding domain-specific memory B cell, and neutralizing antibody responses. KTXs also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals and suggest a GC origin for certain humoral and memory B cell responses following mRNA vaccination.

Potential for the Biodegradation of Atrazine Using Leaf Litter Fungi from a Subtropical Protection Area.

The intense use of pesticides in agricultural activities for the last several decades has caused contamination of the ecosystems connected with crop fields. Despite the well-documented occurrence of pesticide biodegradation by microbes, natural attenuation of atrazine (ATZ), and its effects on ecological processes in subtropical forested areas, such as Iguaçu National Park located in Brazil, has been poorly investigated. Subtropical environments sustain a great degree of fungal biodiversity, and the patterns and roles of these organisms should be better understood. This work aimed to evaluate nine ligninolytic-producer fungi isolated from the INP edge to degrade and detoxify ATZ solutions. ATZ degradation and the main metabolites produced, including deisopropylatrazine and deethylatrazine (DEA), were analyzed using dispersive liquid-liquid microextraction followed by gas chromatography-mass spectrometer. Four fungi were able to degrade ATZ to DEA, and the other five showed potential to grow and facilitate ATZ biodegradation. Furthermore, two strains of Fusarium spp. showed an enhanced potential for detoxification according to the Allium cepa (onion) test. Although the isolates produced ligninolytic enzymes, no ligninolytic activity was observed in the biodegradation of ATZ, a feature with ecological significance. In conclusion, Ascomycota fungi from the INP edge can degrade and detoxify ATZ in solution. Increasing the knowledge of biodiversity in subtropical protected areas, such as ecosystem services provided by microbes, enhances ecosystem conservation.

Conocimientos, prácticas y prevalencia de uso de medidas de protección adecuada frente a la radiación ultravioleta en habitantes de Bogotá D.C. (2013-2018) / Knowledges, practices, and prevalence of the use of appropriate protective measures facing ultraviolet radiation (UVR) in inhabitants of Bogotá D.C. (2013-2018) / Conhecimento, práticas e prevalência do uso de medidas de proteção adequadas contra a radiação ultravioleta em habitantes de Bogotá D.C. (2013-2018)

Objetivo: describir los conocimientos, las prácticas y la prevalencia de uso de medidas de protección adecuadas frente a la radiación ultravioleta (RUV) en una muestra de habitantes de Bogotá D.C., Colombia (2013-2018). Método: estudio de corte transversal a partir de encuestas realizadas por la Secretaría Distrital de Salud (SDS) en diferentes sectores de Bogotá. Se entrevistaron transeúntes de áreas públicas de concentración masiva en las 20 localidades de Bogotá, los cuales fueron incluidos de forma secuencial y por conveniencia. Se estudiaron aspectos sociodemográficos, fenotípicos, antecedente de interés, conocimientos y prácticas relacionadas con la exposición a la RUV. Resultados: se analizaron 8.420 encuestas, donde el 66 % (n: 5.560) eran sujetos de género femenino, con una mediana de edad de 38 años. La mayoría de los encuestados se ubicaron en los estratos socioeconómicos del I al III (95,6 %; n: 8.051). El 27 % declaró una ocupación laboral al aire libre (n: 2.268) y el 50 % reportaron exponerse a la RUV los siete días de la semana (n: 4.255). El 70 % de los participantes (n: 5.870) reconoció que la RUV es un factor de riesgo de cáncer de piel, pero tan sólo el 20,8 % (n: 1.753) reportó prácticas adecuadas de protección. Conclusiones: a pesar del alto nivel de conocimiento frente a los riesgos de la RUV existe un bajo porcentaje de uso de medidas de protección en esta muestra de habitantes de Bogotá. Se deben reforzar las estrategias que conduzcan a incrementar la protección frente a la RUV en este grupo poblacional.

Objective: To describe knowledge, practices, and prevalence of the use of appropriate protective measures facing ultraviolet radiation (UVR) in a sample of inhabitants of Bogotá D.C., Colombia (2013-2018). Method: A cross-sectional study from surveys carried out by the District Secretariat of Health (SDS according to its Spanish initials) in different sectors of Bogotá. Transients of public areas of mass concentration in 20 localities of Bogotá were interviewed. These were included in a sequential way and by convenience. Sociodemographic, phenotype aspects were studied, along with interests, knowledge, and practices related to UVR exposure. Results: 8,420 surveys were analyzed, where 66% (n: 5,560) were female, with an average age of 38 years. Most people surveyed were in socioeconomic levels I to III (95.6%; n: 8,051). 27% declared that they worked outside (n: 2,268), and 50% reported exposure to UVR seven days a week (n: 4,255). 70% of participants (n: 5,870) recognized that UVR is a skin cancer risk factor, but only 20.8% (n: 1,753) reported appropriate protection measures. Conclusions: Despite high levels of knowledge regarding the risk of UVR, there is a low level of use of protection measures in this sample of inhabitants in Bogotá. Strategies must be reinforced that lead to an increase of protection against UVR in this population group.

Objetivo: descrever os conhecimentos, as práticas e a prevalência do uso de medidas de proteção adequadas contra a radiação ultravioleta (RUV) em uma amostra de habitantes de Bogotá D.C., Colômbia (2013-2018). Método: estudo transversal baseado em inquéritos realizados pela Secretaria Distrital de Saúde (SDS) em diferentes setores de Bogotá. Foram entrevistados transeuntes de áreas públicas de maior concentração nas 20 localidades de Bogotá; eles foram incluídos sequencialmente e por conveniência. Foram estudados aspectos sociodemográficos e fenotípicos, histórico de interesse, conhecimentos e práticas relacionadas à exposição à RUV. Resultados: foram analisados 8.420 inquéritos, dos quais 66% (n: 5.560) eram do sexo feminino, com mediana de idade de 38 anos. A maioria dos entrevistados estava localizados nos estratos socioeconômicos de I a III (95,6%; n: 8.051). 27% declararam ocupação ao ar livre (n: 2.268) e 50% relataram exposição à RUV sete dias por semana (n: 4.255). 70% dos participantes (n: 5.870) reconheceram que a RUV é um fator de risco para câncer de pele, mas apenas 20,8% (n: 1.753) relataram práticas de proteção adequadas. Conclusões: apesar do alto nível de conhecimento sobre os riscos da RUV, há um baixo percentual de uso de medidas de proteção nesta amostra de habitantes de Bogotá. Estratégias que levem ao aumento da proteção contra RUV nesse grupo populacional devem ser reforçadas.

SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation.

The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms-mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant-looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer's Disease Leads to Neuroglial and Endothelial Cell Degeneration.

Evidence suggests that extracellular vesicles (EVs) act as mediators and biomarkers of neurodegenerative diseases. Two distinct forms of Alzheimer disease (AD) are known: a late-onset sporadic form (SAD) and an early-onset familial form (FAD). Recently, neurovascular dysfunction and altered systemic immunological components have been linked to AD neurodegeneration. Therefore, we characterized systemic-EVs from postmortem SAD and FAD patients and evaluated their effects on neuroglial and endothelial cells. We found increase CLN-5 spots with vesicular morphology in the abluminal portion of vessels from SAD patients. Both forms of AD were associated with larger and more numerous systemic EVs. Specifically, SAD patients showed an increase in endothelial- and leukocyte-derived EVs containing mitochondria; in contrast, FAD patients showed an increase in platelet-derived EVs. We detected a differential protein composition for SAD- and FAD-EVs associated with the coagulation cascade, inflammation, and lipid-carbohydrate metabolism. Using mono- and cocultures (endothelium-astrocytes-neurons) and human cortical organoids, we showed that AD-EVs induced cytotoxicity. Both forms of AD featured decreased neuronal branches area and astrocytic hyperreactivity, but SAD-EVs led to greater endothelial detrimental effects than FAD-EVs. In addition, FAD- and SAD-EVs affected calcium dynamics in a cortical organoid model. Our findings indicate that the phenotype of systemic AD-EVs is differentially defined by the etiopathology of the disease (SAD or FAD), which results in a differential alteration of the NVU cells implied in neurodegeneration.

A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.

SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.

Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition.

BACKGROUND AND AIMS: B cells involvement in animal models of atherosclerosis has been unequivocally established. However, the role of these cells in patients with atherosclerosis is almost unknown. Besides the production of antibodies, B cells can also exhibit regulatory functions mainly through IL-10. Here, we characterized human B cell subsets, their production of IL-10 in patients with atherosclerosis and their potential association with inflammation. METHODS: Patients with confirmed atherosclerotic events and controls with low cardiovascular risk were included. B cells subsets were determined in mononuclear cells (PBMC) using flow cytometry. PBMC were cultured ex vivo (5 h) and in vitro (48 h) to determine IL-10+ B cells and in some cases TNF-α+ and IFN-γ+ CD4+ T cells. The inflammatory state of the participants was determined through high sensitivity C reactive protein levels. RESULTS: Increase in percentage and number of plasmablasts was observed in patients with atherosclerosis compared with controls. A decreased frequency of IL-10+ B cells was observed in patients, both in ex vivo and in vitro cultures. This decrease was detected in transitional, memory, and plasmablast subsets. Interestingly, the reduction of IL-10+ B cells negatively and significantly correlated with the inflammatory condition of the studied subjects and associated with an increased frequency of TNF-α+ and IFN-γ+ CD4+ T cells. The blockade of IL-10R did not show further effect in T cells activation. CONCLUSIONS: There is an association between the inflammatory state and a reduction of IL-10+ B cells that could contribute to the development of atherosclerosis.

Induction of NF-κB inflammatory pathway in monocytes by microparticles from patients with systemic lupus erythematosus.

BACKGROUND: Elevated levels of circulating microparticles (MPs) and molecules of the complement system have been reported in patients with systemic lupus erythematosus (SLE). Moreover, microparticles isolated from patients with SLE (SLE-MPs) contain higher levels of damage-associated molecular patterns (DAMPs) than MPs from healthy controls (CMPs). We hypothesize that the uptake of MPs by monocytes could contribute to the chronic inflammatory processes observed in patients with SLE. Therefore, the aim of this study was to evaluate the expression of activation markers, production of proinflammatory mediators, and activation of the NF-κB signaling pathway in monocytes treated with CMPs and SLE-MPs. METHODOLOGY: Monocytes isolated from healthy individuals were pretreated or not with pyrrolidine dithiocarbamate (PDTC) and cultured with CMPs and SLE-MPs. The cell surface expression of CD69 and HLA-DR were evaluated by flow cytometry; cytokine and eicosanoid levels were quantified in culture supernatants by Cytokine Bead Array and ELISA, respectively; and the NF-κB activation was evaluated by Western blot and epifluorescence microscopy. RESULTS: The cell surface expression of HLA-DR and CD69, and the supernatant levels of IL-6, IL-1ß, PGE2, and LTB4 were higher in cultures of monocytes treated with SLE-MPs than CMPs. These responses were blocked in the presence of PDTC, a pharmacological inhibitor of the NF-κB pathway, with concomitant reduction of IκBα and cytoplasmic p65, and increased nuclear translocation of p65. CONCLUSIONS: The present findings indicate that significant uptake of SLE-MPs by monocytes results in activation, production of inflammatory mediators, and triggering of the NF-κB signaling pathway.

Proinflammatory Differentiation of Macrophages Through Microparticles That Form Immune Complexes Leads to T- and B-Cell Activation in Systemic Autoimmune Diseases.

Patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) demonstrate increased circulating microparticles (MP). These vesicles, primarily those that form immune complexes (MP-IC), may activate monocytes. We evaluated the effect of MP and MP-IC in the differentiation of monocytes to macrophages (monocyte-derived macrophages; MDM) and for consequences in autologous lymphocyte activation. Monocytes from healthy controls (HC) and patients with RA and SLE that differentiated into MDM in the presence of MP-IC showed a proinflammatory (M1-like) profile, which was more evident using MP-IC from patients with RA than those from patients with SLE. Notably, MDM from HC and patients with RA that differentiated with MP-IC were more prone to M1-like profile than those from patients with SLE. In HC and patients with RA, monocyte differentiation using MP-IC decreased the frequency of MDM that bound/internalized latex beads. The M1-like profile did not completely revert following IL-4 treatment. The effect of M1-like MDM on T lymphocytes stimulated with phytohemagglutinin was further evaluated. MDM differentiated with MP enhanced the proliferation of T cells obtained from patients with RA compared with those differentiated with MP-IC or without vesicles. Neither MP nor MP-IC induced interferon (IFN)-γ+ and tumor necrosis factor (TNF)-α+ T cells in patients with RA. Conversely, unlike MDM differentiated with or without MP, MP-IC enhanced the proliferation and increased the frequencies of IFN-γ+CD4+ T, TNF-α+CD4+ T, and IFN-γ+CD8+ T cells in patients with SLE. The co-culture of B cells with MDM obtained from patients with RA and SLE and differentiated with MP-IC increased the expression of B-cell activation markers and prevented B lymphocyte death. Strikingly, only for patients with SLE, these responses seemed to be associated with a significant increase in B-cell activating factor levels, high plasmablast frequency and immunoglobulin production. These results showed that MP-IC from patients with systemic autoimmune diseases favored the polarization of MDM into a proinflammatory profile that promotes T-cell activation, and additionally induced B-cell activation and survival. Therefore, the effect of MP-IC in mononuclear phagocytes may be an important factor for modulating adaptive responses in systemic autoimmune diseases.

Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: Endothelial activation and damage is commonly observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is related to development of atherosclerosis and cardiovascular diseases. Different components of the immune system seem to participate in the endothelial injury, such as generation of autoantibodies and formation of immune complexes (ICs). Microparticles (MPs) and their immune complexes (MPs-ICs) are increased in the circulation of patients with SLE and RA; therefore, we propose these extracellular vesicles could interact and modulate the function of endothelial cells. Hence, the effect of MPs and MPs-ICs from patients with SLE and RA in endothelial cells was evaluated. METHODS: Macrovascular and microvascular endothelial cells were exposed to MPs and MPs-ICs from healthy donors and patients with SLE and RA. Vesicles uptake/binding, expression of adhesion molecules, cytokine and chemokine production, monocyte adherence, and alterations of endothelial monolayer were evaluated by flow cytometry and fluorescence microscopy. RESULTS: Endothelial cells internalized MPs and MPs-ICs and increased CD54 and CD102 expression and CCL2, CCL5, and IL-6 production after the treatment with these extracellular vesicles, which led to an increase in the adherence of classic monocytes. These vesicles also induced low expression of VE-cadherin in membrane, depolymerization of actin filaments, and formation of intercellular spaces, which led to endothelial death and increased permeability after MPs and MPs-ICs exposure. CONCLUSIONS: MPs and MPs-ICs from patients with SLE and RA increase adhesion molecules expression, chemokine production, and structural alterations in macrovascular and microvascular endothelial cells. Therefore, high counts of these vesicles in patients would promote endothelial alterations and secondary tissue leukocyte infiltration.

Different phenotypes of non-classical monocytes associated with systemic inflammation, endothelial alteration and hepatic compromise in patients with dengue.

Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non-classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor-α+ cells and exposure of phosphatidylserine, were recorded in the non-classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non-classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin-6 (IL-6), IL-8 and IL-10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non-classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor-α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non-classical monocytes seem to be associated with the immunopathology of dengue infection.

HMGB1+ microparticles present in urine are hallmarks of nephritis in patients with systemic lupus erythematosus.

Non-classical monocytes infiltrate the kidney parenchyma and participate in tissue damage in patients with lupus nephritis (LN). Circulating microparticles (MPs) seem to play critical roles in the activation of monocytes in systemic lupus erythematosus (SLE) patients. This study aims to characterize the phenotypes of MPs and monocyte subsets in LN patients and to determine their potential to discriminate between SLE patients with and without LN. Blood and urine samples from SLE patients were collected. In monocyte subsets from whole blood samples several phenotypic markers were evaluated. MPs were isolated from platelet-poor plasma and urine by centrifugation. This phenotypic marker characterization was performed using multiparametric flow cytometry. We observed that patients with active LN have lower counts of non-classical monocytes than do those without renal involvement. All monocyte subsets exhibited lower expression of CX3CR1 and ICAM-1 in LN than in patients without LN. High frequencies of MP-HMGB1+ and MP-HLA-DR+ were detected in circulation and urine of LN patients. Although MP-HMGB1+ , MP-HLA-DR+ , and MP-CX3CR1+ from urine were able to discriminate between patients with and without LN, only urinary MP-HMGB1+ were different between patients with active and inactive LN. Therefore, these vesicles may be useful as biomarkers of LN.

Platelet-derived microparticles generated in vitro resemble circulating vesicles of patients with rheumatoid arthritis and activate monocytes.

Patients with rheumatoid arthritis (RA) have increased amount of platelet-derived microparticles (PMPs) positive for citrullinated peptides (CPs) that form immune complexes (PMPs-ICs). Monocytes are important inflammatory mediators that play a role in the clearance of PMPs-ICs. We aimed to generate PMPs-ICs in vitro and determine its effect on monocytes from patients with RA and healthy individuals (HI). PMPs from patients showed platelet markers, mitochondria content, and phosphatidylserine exposure similar to PMPs from HI. However, patients had a higher frequency of IgG+ and CPs+ vesicles than HI. PMPs-ICs generated in vitro were similar to the circulating vesicles of patients with respect to IgG- and CPs-positivity. PMPs-ICs induced pro-inflammatory cytokines and CX3CR1 expression in monocytes from HI, and IL-10 and CD36 upregulation in monocytes from patients. These results suggest that PMPs-ICs induce activation of monocytes, with a pro-inflammatory response in HI and a more tolerant response in cells of patients with RA.

Role of Monocytes in the Pathogenesis of Dengue.

Diseases caused by dengue virus (DENV) are a major public health problem worldwide, considered one of the infections with more prevalence in tropical and subtropical zones of the world. Despite the intense research in the pathogenesis of DENV, this feature is not well understood. One of the main target cells for DENV infection is monocytes; these phagocytes can play a dual role, since they are essential to control viremia, but they also participate in the induction of tissue damage during DENV infection. Monocytes produce different pro-inflammatory cytokines and chemokines in response to infection, and also mediate endothelial damage. In peripheral blood, monocytes can be divided into three different subpopulations, namely classical, intermediate and non-classical, which differ in frequency, cytokine production, among others. Studies in the last years suggest that non-classical monocytes have higher affinity for microvasculature endothelium compared to other type of monocytes, which implies that they could be more involved in the increase of endothelial permeability observed during DENV infection. This review provides a general view of the role of monocytes and their subpopulations in DENV pathogenesis and its effect in viral replication. Finally, the potential contribution of these phagocytes in the alterations of endothelial permeability is discussed.

Extracellular vesicles are associated with the systemic inflammation of patients with seropositive rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) and autoantibodies, such as rheumatoid factor and those against cyclic citrullinated peptides, are designated as seropositive and have a more severe disease with worse prognosis than seronegative RA patients. Understanding the factors that participate in systemic inflammation, in addition to articular commitment, would allow better treatment approaches for prevention of RA comorbidities and disease reactivation. We evaluated whether monocyte subsets and extracellular vesicles (EVs) could contribute to this phenomenon. Seropositive patients had higher levels of proinflammatory cytokines than those of seronegative patients and healthy controls (HCs); however, this systemic inflammatory profile was unrelated to disease activity. High frequencies of circulating EVs positive for IgG, IgM, CD41a, and citrulline, together with altered counts and receptor expression of intermediate monocytes, were associated with systemic inflammation in seropositive patients; these alterations were not observed in seronegative patients, which seem to be more similar to HCs. Additionally, the EVs from seropositive patients were able to activate mononuclear phagocytes in vitro, and induced proinflammatory cytokines that were comparable to the inflammatory response observed at the systemic level in seropositive RA patients; therefore, all of these factors may contribute to the greater disease severity that has been described in these patients.

Factores de riesgo y enfermedades cardiometabólicas en Risaralda 2017 proyectada a 2050 / Risk factors and cardiometabolic disease in Risaralda 2017 to 2050

Resumen Objetivo: Proyectar el comportamiento de factores de riesgo y de la incidencia de dos enfermedades cardiometabólicas, en una población colombiana entre 2017 y 2050. Metodología: Diseño de cohorte abierta basado en un modelo de microsimulación dinámica para la población adulta de Risaralda, Colombia. Los factores de riesgo analizados son tabaquismo, obesidad global, obesidad central y colesterol total. Se creó una población sintética que replica las características demográficas y de salud de Risaralda en 2010, utilizando algoritmos de emparejamiento e imputación estadística. La evolución a lo largo del curso de vida se simuló basada en reglas derivadas de la literatura, con ecuaciones estocásticas y modelos econométricos. Se calcula la incidencia de diabetes tipo II y de eventos cerebrovasculares isquémicos de 2017 a 2050. Resultados: En 2050, 16.7 % serán fumadores, la tercera parte de ellos presentarán obesidad global y más de la mitad presentarán obesidad central. El promedio de colesterol total aumentará 5 mg/dL. Adicionalmente, se espera que entre 2017 y 2050 se presenten 204.966 casos nuevos de diabetes y 65.758 eventos cerebrovasculares isquémicos. Conclusiones: Los estilos de vida y el envejecimiento poblacional, llevarán a mayor exposición a riesgo y aumentarán la velocidad a la que los risaraldenses se enfermarán de Diabetes y experimentarán eventos cerebrovasculares. La obesidad global y central son factores que explicarían esta tendencia. Se requieren intervenciones intersectoriales que protejan a la población y reduzcan cargas fiscales por condiciones evitables.

Abstract Objective: predict the behavior of the risk factors and the incidence of two cardiometabolic diseases in a population from Colombia between 2017 and 2050. Methodology: Follow up of individual's cohort of an artificial society of Risaralda, Colombia, based on a microsimulation model. The risk factors analyzed in this study are tobacco use, obesity, central obesity and total cholesterol. A synthetic population was created to replicate demographic and health characteristics of Risaralda in 2010, using pairing algorithms and statistical imputation. The evolution along the life course was simulated based on rules from scientific literature, with stochastic equations and econometric estimates. The incidence of type II diabetes and ischemic stroke is calculated for the adult population between 2017 to 2050. Results: 16.7% of the adults by 2050 is expected to be smokers, a third of them will have global obesity and more than half will have central obesity. The average level of serum total cholesterol would increase by 5 mg/dL. Additionally, is expected that between 2017 and 2050 there will be 204.966 incident cases of diabetes and 65.758 first-ever ischemic stroke events. Conclusions: Lifestyles and expected population aging will lead to greater risk of disease and will increase the rate at which local people will get diabetes and ischemic stroke. Risk factors like global and central obesity explain this trend. Effective intersectoral interventions are needed to protect the population and reduce tax burden due to preventable conditions.