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Mortality rate in patients with COVID-19 increases in those admitted to the ICU. Activation of the coagulation system is associated with the worse disease outcomes. The aim of this study was to evaluate platelet activation and thrombotic biomarkers in hospitalized patients with COVID-19 during the second and third infection waves of the pandemic during 2021, following a previous report that included patients from the first wave. Sixty five patients were recruited and classified according to disease outcome; 10 healthy donors were included as a control group. Among prothrombotic biomarkers, t-PA concentrations ( p

Background: Zika (ZIKV) is a mosquito-borne virus that has caused multiple outbreaks in Americas. The early and accurate diagnosis of ZIKV is the key to minimize the health burden imposed on the infected patients. Many commercial ZIKV diagnosis kit are available based on ZIKV envelope antigen with varying sensitivity and specificity. Objective: The aim of this study was to develop sensitive ELISA methodology based on recombinant ZIKV NS1 and NS1 β-ladder antigens for seroprevalence detection in a cohort of patients in an arbovirus endemic Mexican region in comparison to a commercial kit. Study design: We obtained serum samples from 60 patients presenting with febrile illness and from 10 healthy donors in Michoacán state in 2016–2017. These samples were screened for ZIKV by RT-PCR and used to develop NS1 based ELISA and compared to a commercial kit. Results: Our results indicate that both ZIKV sNS1 and β-ladder-based ELISA can reliably detect anti-ZIKV NS1 antibodies in infected patients, relevant for the serodiagnosis of ZIKV. Determination of antibody titers showed that it offered higher sensitivity than a commercially available ZIKV ELISA. Over 90% seropositivity against ZIKV for the febrile patients was detected in Lázaro Cárdenas which is an arbovirus endemic region while lower seropositivity was observed in the healthy volunteers in Morelia (non-endemic area). Conclusion: We conclude that our simple and sensitive in-house NS1 based ELISA used in this study has excellent sensitivity, is easy to use and can provide fast results suitable for larger population-based seroprevalence studies in the future.

Among COVID-19 hospitalized patients, high incidence of alterations in inflammatory and coagulation biomarkers correlates with a poor prognosis. Comorbidities such as chronic degenerative diseases are frequently associated with complications in COVID-19 patients. The aim of this study was to evaluate inflammatory and procoagulant biomarkers in COVID-19 patients from a public hospital in Mexico. Blood was sampled within the first 48 h after admission in 119 confirmed COVID-19 patients that were classified in 3 groups according to oxygen demand, evolution and the severity of the disease as follows: 1) Non severe: nasal cannula or oxygen mask; 2) Severe: high flow nasal cannula and 3) Death: mechanical ventilation eventually leading to fatal outcome. Blood samples from 20 healthy donors were included as a Control Group. Analysis of inflammatory and coagulation biomarkers including D-dimer, interleukin 6, interleukin 8, PAI-1, P-selectin and VWF was performed in plasma. Routine laboratory and clinical biomarkers were also included and compared among groups. Concentrations of D-dimer (14.5 ± 13.8 µg/ml) and PAI-1 (1223 ± 889.6 ng/ml) were significantly elevated in severe COVID-19 patients (P < 0.0001). A significant difference was found in interleukin-6, PAI-1 and P-selectin in non-severe and healthy donors when compared to Severe COVID-19 and deceased patients (P < 0.001). VWF levels were also significantly different between severe patients (153.5 ± 24.3 UI/dl) and non-severe ones (133.9 ± 20.2 UI/dl) (P < 0.0001). WBC and glucose levels were also significantly elevated in patients with Severe COVID-19. Plasma concentrations of all prothrombotic biomarkers were significantly higher in patients with a fatal outcome.

Obesity (OB) is a major healthcare problem that results from long-term energy imbalance. Adipokines and pro-inflammatory cytokines facilitate adipose tissue (AT) remodeling to safely store excess nutrients. B-cell activating factor (BAFF) is a newly described adipokine whose role in enhancing adipogenesis has been reported. The present study aimed to evaluate serum BAFF association with adiposity distribution, serum adipokines, pro-inflammatory cytokines, and metabolic and endothelial dysfunction markers. The study included 124 young Mexican adults with no diagnosed comorbidities, divided according to their BMI. Anthropometric measurements, blood counts, and serum molecules (i.e., glucose, lipid profile, insulin, leptin, pro- and anti-inflammatory cytokines, von Willebrand factor (vWF), and BAFF) were assessed. The analysis showed positive correlation between BAFF and increased fat mass in all anthropometric measurements (p < 0.0001). BAFF augmentation was related to systemic inflammatory environment (p < 0.05), and linked with insulin resistance status (p < 0.05). BAFF increment was also correlated with early endothelial damage markers such as vWF (p < 0.0001). Linear regression analysis showed a role for BAFF in predicting serum vWF concentrations (p < 0.01). In conclusion, our data show that BAFF is an adipokine dynamically related to OB progression, insulin resistance status, and systemic inflammatory environment, and is a predictor of soluble vWF augmentation, in young overweight and obese Mexican subjects.

Abstract Background Zika virus (ZIKV) has become a global threat with immediate need for accurate diagnostics, efficacious vaccines and therapeutics. Several ZIKV envelope (Env)-based vaccines have been developed recently. However, many commercially available ZIKV Env are based on the African lineage and produced in insect cells. Here, we sought to produce Asian-lineage ZIKV Env in mammalian cells for research and clinical applications. Methods We designed various gene expression constructs to optimize the production of ZIKV using prM-Env and full or C-terminal truncations of Env; with or without a rat CD4 fusion partner to allow large-scale production of soluble protein in mammalian HEK293 cells. Protein expression was verified by mass spectrometry and western-blot with a pan-flavivirus antibody, a ZIKV Env monoclonal antibody and with immune sera from adenoviral (ChAdOx1) ZIKV Env-vaccinated mice. The resulting Env-CD4 was used as a coating reagent for immunoassay (ELISA) using both mouse and human seropositive sera. Results Replacement of the C-terminus transmembrane Env domain by a rat CD4 and addition of prM supported optimal expression and secretion of Env. Binding between the antigens and the antibodies was similar to binding when using commercially available ZIKV Env reagents. Furthermore, antibodies from ZIKV patients bound ZIKV Env-CD4 in ELISA assays, whereas sera from healthy blood donors yielded minimal OD background. The serological outcomes of this assay correlated also with ZIKV neutralisation capacity in vitro. Conclusions Results obtained from this study indicate the potential of the Asian-lineage Zika Env-CD4 and Env proteins in ELISA assays to monitor humoral immune responses in upcoming clinical trials as well as a sero-diagnostic tool in ZIKV infection.

Introduction: Low levels of thyroid hormones, total triiodothyronine (T3) and free triiodothyronine (FT3) in haemodialysis patients are a marker of malnutrition and inflammation and are predictors of mortality. The aim of this study was to determine the prevalence of malnutrition-inflammation complex syndrome in haemodialysis and its relationship with the thyroid hormones thyrotropin, T3, FT3 and free thyroxine (FT4), as well as to evaluate the prevalence of low FT3 syndrome and its correlation with nutritional and inflammatory markers. Materials and methods: Cross-sectional, analytical and comparative study that enrolled 128 haemodialysis patients: 50.8% females; mean age 45.05 ± 17.01 years; mean time on haemodialysis 45.4 ± 38.8 months; 29.7% diabetics; 79.7% with hypertension. Serum thyroidhormones thyrotropin, T3, FT3 and FT4 concentrations were measured and Malnutrition-Inflammation Score (MIS) was applied to diagnostic. Results: Mean thyroid hormone values were: thyroid hormones thyrotropin 2.48 ± 1.8 mIU/ml (range: 0.015–9.5), T3 1.18 ± 0.39 ng/ml (range 0.67–2.64), FT3 5.21 ± 0.96 pmol/l (range: 3.47–9.75); FT4 1.35 ± 0.4 ng/ml (range: 0.52–2.57). Malnutrition-inflammation complex syndrome prevalence was 53.9%; 11.7% presented low FT3 levels. Serum T3 and FT3 concentrations inversely correlated with Malnutrition-Inflammation Score (MIS), while FT4 correlated positively with Malnutrition-Inflammation Score. In the linear regression analysis, low FT3 was associated with IL-6 (β = 0.265, p = .031), C-reactive protein (CRP) (β = −0.313, p = .018) and albumin (β = 0.276, p = .002). Conclusion: Low T3 and FT3 levels are correlated with malnutrition and inflammation parameters. Malnutrition-inflammation complex syndrome can affect serum concentrations of thyroid hormones.

Introducción: La reducción de las hormonas tiroideas, triyodotironina total (T3) y triyodotironina libre (T3L) en pacientes en hemodiálisis, es un marcador de malnutrición e inflamación y son predictores de mortalidad. El objetivo del estudio fue determinar la prevalencia del síndrome complejo de malnutrición e inflamación en hemodiálisis y su asociación con las hormonas tiroideas: tirotropina, T3, T3L y tiroxina libre (T4L); además de evaluar la incidencia del síndrome de T3L y su correlación con marcadores nutricionales e inflamatorios. Materiales y métodos: Estudio transversal, analítico y comparativo, incluyó 128 pacientes en HD, 50,8% mujeres, edad 45,05 ± 17,01 años, 45,4 ± 38,8 meses en hemodiálisis, 29,7% diabéticos y 79,7% hipertensos. Se determinó en suero la concentración de tirotropina, T3, T3L y T4L, se aplicó la encuesta Malnutrition-Inflammation Score para diagnosticar malnutrición e inflamación. Resultados: La media de valores de las hormonas tiroideas fueron: tirotropina 2,48 ± 1,8 mUI/mL (rango 0,015-9,5), T3 1,18 ± 0,39ng/mL (0,67-2,64), T3L 5,21 ± 0,96 pmol/l (3,47-9,75), T4L 1,35 ± 0,4ng/mL (0,52-2,57). La prevalencia de síndrome complejo de malnutrición e inflamación es 53,9%; un 11,7% mostró T3L baja. Las concentraciones séricas de T3 y T3L correlacionan negativamente con Malnutrition-Inflammation Score y T4L correlaciona positivamente con Malnutrition-Inflammation Score. El análisis de regresión lineal de T3L baja fue asociado con IL-6 (β=0,265 p = 0,031), proteína C reactiva (β=-0,313 p = 0,018) y albúmina (β=0,276 p = 0,002). Conclusiones: Bajos niveles de T3 y T3L correlacionan con parámetros de inflamación y nutrición. El síndrome complejo de malnutrición e inflamación puede afectar la concentración sérica de hormonas tiroideas.

Chikungunya fever is a debilitating disease caused by Chikungunya virus (CHIKV) that can result in long-lasting arthralgias. The early diagnosis of CHIKV relies on PCR during the acute infection phase to allow differential diagnosis with other co-circulating arboviruses such as dengue and Zika. Alternatively, serology can support diagnosis and provide epidemiological information on current and past outbreaks. Many commercial serological ELISA assays are based on the inactivated whole CHIKV, but their sensitivity and specificity show great variability. We produced recombinant CHIKV E2 that is suitable for ELISA assays, which was used for the serodiagnosis of CHIKV infections occurring in an arbovirus endemic Mexican region within Michoacán state. A cross-sectional study was conducted in 2016−2017; sera was obtained from 15 healthy donors and 68 patients presenting undifferentiated febrile illness. Serum samples were screened by RT-PCR and by our in-house ELISA assay. Our results indicate that IgM and IgG anti-CHIKV E2 antibodies were detected with our ELISA assay with higher sensitivity than a commercially available CHIKV ELISA kit. Our simple and sensitive ELISA assay for the serodiagnosis of CHIKV infections can be applied to population-based seroprevalence surveys and has potential for monitoring vaccine immunogenicity in CHIKV vaccine clinical trials.

Obesity (OB) is a major healthcare problem that results from long-term energy imbalance. Adipokines and pro-inflammatory cytokines facilitate adipose tissue (AT) remodeling to safely store excess nutrients. B-cell activating factor (BAFF) is a newly described adipokine whose role in enhancing adipogenesis has been reported. The present study aimed to evaluate serum BAFF association with adiposity distribution, serum adipokines, pro-inflammatory cytokines, and metabolic and endothelial dysfunction markers. The study included 124 young Mexican adults with no diagnosed comorbidities, divided according to their BMI. Anthropometric measurements, blood counts, and serum molecules (i.e., glucose, lipid profile, insulin, leptin, pro- and anti-inflammatory cytokines, von Willebrand factor (vWF), and BAFF) were assessed. The analysis showed positive correlation between BAFF and increased fat mass in all anthropometric measurements (p < 0.0001). BAFF augmentation was related to systemic inflammatory environment (p < 0.05), and linked with insulin resistance status (p < 0.05). BAFF increment was also correlated with early endothelial damage markers such as vWF (p < 0.0001). Linear regression analysis showed a role for BAFF in predicting serum vWF concentrations (p < 0.01). In conclusion, our data show that BAFF is an adipokine dynamically related to OB progression, insulin resistance status, and systemic inflammatory environment, and is a predictor of soluble vWF augmentation, in young overweight and obese Mexican subjects. [ABSTRACT FROM AUTHOR]

Objective: To investigate the factors associated with platelet activation in obese children. Design: Cross-sectional study. Setting: Department of Pediatrics of Regional Hospital N° I of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants: 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures: Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 nonobese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results: Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.21 I ; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:-0.215; t:-2.819; P=0.006). Conclusions: Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. [ABSTRACT FROM AUTHOR]