RESUMEN
Diabetic foot ulcer is one of the most frightened diabetic complications leading to amputation disability and early mortality. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, and reactive oxygen and nitrogen species as a pathogenic polymicrobial biofilm, overall contributing to wound chronification and host homeostasis imbalance. Intralesional infiltration of epidermal growth factor (EGF) has emerged as a therapeutic alternative to diabetic wound healing, reaching responsive cells while avoiding the deleterious effect of proteases and the biofilm on the wound's surface. The present study shows that intralesional therapy with EGF is associated with the systemic attenuation of pro-inflammatory markers along with redox balance recovery. A total of 11 diabetic patients with neuropathic foot ulcers were studied before and 3 weeks after starting EGF treatment. Evaluations comprised plasma levels of pro-inflammatory, redox balance, and glycation markers. Pro-inflammatory markers such as erythrosedimentation rate, C-reactive protein, interleukin-6, soluble FAS, and macrophage inflammatory protein 1-alpha were significantly reduced by EGF therapy. Oxidative capacity, nitrite/nitrate ratio, and pentosidine were also reduced, while soluble receptor for advanced glycation end-products significantly increased. Overall, our results indicate that the local intralesional infiltration of EGF translates in systemic anti-inflammatory and antioxidant effects, as in attenuation of the glycation products' negative effects.
Asunto(s)
Pie Diabético/tratamiento farmacológico , Factor de Crecimiento Epidérmico/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Anciano , Arginina/análogos & derivados , Arginina/sangre , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Quimiocina CCL3/sangre , Citocinas/sangre , Femenino , Humanos , Inyecciones Intralesiones , Lisina/análogos & derivados , Lisina/sangre , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Receptor para Productos Finales de Glicación Avanzada/sangre , Cicatrización de Heridas , Receptor fas/sangreRESUMEN
In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.
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Quimiocina CCL24/sangre , Quimiocina CCL3/sangre , Quimiocina CCL7/sangre , Oxidorreductasas Intramoleculares/sangre , Cirrosis Hepática/inmunología , Factores Inhibidores de la Migración de Macrófagos/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Adolescente , Adulto , Anciano , Animales , Humanos , Hígado/irrigación sanguínea , Hígado/parasitología , Hígado/patología , Cirrosis Hepática/parasitología , Persona de Mediana Edad , Vena Porta/patología , Esquistosomiasis mansoni/parasitología , Adulto JovenRESUMEN
The aim of this study was to investigate the plasma levels of the CCL3 and CCL4 chemokines in patients with the cardiac and digestive clinical forms of chronic Chagas disease and in cardiac patients with and without left ventricular systolic dysfunction (LVSD). Plasma samples from 75 patients were evaluated by enzyme-linked immunosorbent assay (ELISA) to confirm infection by T. cruzi. Plasma levels of the CCL3 and CCL4 chemokines were measured using Milliplex® MAP assay (Millipore). There were no significant differences in the levels of CCL3 and CCL4 between patients with the digestive and cardiac clinical forms of Chagas disease. Moreover, no significant differences were found between patients without LVSD and those with LVSD. Higher CCL3 and CCL4 plasma levels were found in patients with LVSD compared to those with the digestive form of the disease. The CCL3 and CCL4 chemokines might not be involved in differential susceptibility to the digestive and cardiac clinical forms of chronic Chagas disease, and it seems they do not influence the development of LVSD.
Asunto(s)
Enfermedad de Chagas/sangre , Quimiocina CCL3/sangre , Quimiocina CCL4/sangre , Enfermedades Gastrointestinales/sangre , Trypanosoma cruzi , Disfunción Ventricular Izquierda/sangre , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. METHODS: This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. RESULTS: We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. CONCLUSIONS: This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Quimiocina CCL3/sangre , Quimiocina CCL5/sangre , Trastornos Migrañosos/diagnóstico , Cefalea de Tipo Tensional/diagnóstico , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/sangre , Cefalea de Tipo Tensional/sangre , Adulto JovenRESUMEN
ABSTRACT Objectives Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. Methods This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. Results We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. Conclusions This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.
RESUMO Objetivos Moléculas inflamatórias e fatores neurotróficos estão implicados na modulação dolorosa, contudo, seu papel nas cefaleias primárias não é claro. O objetivo do presente estudo foi comparar níveis de biomarcadores séricos na migrânea e cefaleia do tipo tensional. Métodos Este foi um estudo transversal, no qual foram avaliados níveis de adiponectina, quimiocinas e fatores neurotróficos em pacientes com migrânea e cefaleia do tipo tensional. Sintomas depressivos e ansiosos, o impacto e a frequência da cefaleia e alodínea foram registrados. Resultados Foram incluídos 68 pacientes com migrânea e 48 pacientes com cefaleia do tipo tensional. A alodínia cutânea (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), e adiponectina (p = 0.017) foram maiores na migrânea, independentemente de sintomas depressivos e ansiosos, frequência e impacto da cefaleia. Conclusões Níveis de CCL3/MIP-1α, CCL5/RANTES e adiponectina foram maiores na migrânea do que na cefaleia do tipo tensional, sugerindo papeis distintos destas moléculas na fisiopatologia destas duas cefaleias primárias.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Cefalea de Tipo Tensional/diagnóstico , Quimiocina CCL5/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Quimiocina CCL3/sangre , Trastornos Migrañosos/diagnóstico , Biomarcadores/sangre , Estudios Transversales , Cefalea de Tipo Tensional/sangre , Trastornos Migrañosos/sangreRESUMEN
Inflammatory mediators have been studied in migraine pathophysiology; however, their role is not yet well established. The aim of the present study was to investigate interictal chemokine levels and its association with clinical parameters and psychiatric comorbidities in migraine patients compared with controls. This was a cross-sectional study including age and gender matched migraine patients and controls. Beck Depression and Anxiety Inventories, Headache Impact Test, and Allodynia Symptom Checklist were recorded. Chemokines were measured by ELISA. Forty-nine migraine patients and forty-nine controls without headache were included. CXCL8/IL-8 and CCL3/MIP-1α levels were significantly higher among patients with migraine (P = 0.039 and 0.02, respectively) even after controlling for anxiety and depression scores. Chemokine levels were not correlated with migraine impact as well as allodynia scores. CXCL8/IL-8 and CCL3/MIP-1 α levels were raised in migraine, independently of psychiatric comorbidities, migraine impact, and allodynia.
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Quimiocina CCL3/sangre , Interleucina-8/sangre , Trastornos Migrañosos/sangre , Ansiedad/sangre , Ansiedad/complicaciones , Análisis Químico de la Sangre , Comorbilidad , Estudios Transversales , Depresión/sangre , Depresión/complicaciones , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/psicología , Escalas de Valoración PsiquiátricaRESUMEN
Asthma studies suggest that alteration in the inflammation pattern may be associated with the severity of asthma. The aim of this study was to compare in vitro the expression of chemokines, chemokine receptors and cytokine production from CD4+ T human lymphocytes of asthmatic, both obese and non-obese patients with different severity levels of asthma. Lymphocytes were labeled with monoclonal anti-human CXCR3/IP-10, MIP-1a/CCR5 antibodies and were analyzed by flow cytometry. Cell culture supernatants were used to measure production of interleukin IL-6 and resistin by ELISA. CXCR3/IP-10 expression increased in non-obese patients with mild persistent asthma (2.2%, p<0.05), moderate persistent asthma (3%, p<0.003) and severe persistent asthma (4%, p<0.004); this effect was stronger in obese patients with severe persistent asthma (35%, p<0.004). MIP-1 α / CCR5 increased in non-obese patients with intermittent asthma (0.65%, p<0.05) and severe asthma (1.4%, p<0.03); in obese patients, this expression was greater in intermittent asthma (8%, p<0.05) and severe persistent asthma (12%, p<0.04). Resistin production strongly increased in obese patients with intermittent (976 ng/ml) and severe persistent asthma (795 ng/ml). IL-6 increased in both lean and obese persons; however, the highest value was registered in the group of severe persistent obese asthmatics (992 pg/ml). Obesity per se increased the inflammatory profile of chemokines / cytokines secreted by cells of the blood, increasing the inflammatory status in asthmatic patients. Resistin showed characteristics of a pro-inflammatory cytokine mainly in severely obese asthmatics.
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Asma/sangre , Quimiocina CCL3/sangre , Quimiocina CXCL10/sangre , Obesidad/sangre , Receptores de Quimiocina/sangre , Resistina/sangre , Asma/complicaciones , Índice de Masa Corporal , Linfocitos T CD4-Positivos/fisiología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Interleucina-6/sangre , Masculino , Obesidad/complicaciones , Cultivo Primario de Células , Receptores CCR5/sangre , Receptores CXCR3/sangre , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
PURPOSE: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-1-alpha (MIP-1-α) and leukemia inhibitory factor (LIF) in patients with prostate cancer. METHODS AND MATERIALS: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-α, MIP-1-α, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. RESULTS: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-α, MIP-1-α, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-α, MIP-1-α, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. CONCLUSIONS: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-α, MIP-1-α, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.
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Biomarcadores de Tumor/sangre , Citocinas/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/radioterapia , Radioterapia Conformacional/métodos , Anciano , Anciano de 80 o más Años , Quimiocina CCL3/sangre , Humanos , Interleucina-2/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Interleucina-6/sangre , Factor Inhibidor de Leucemia/sangre , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVE: This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia. METHOD: We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-α), two soluble TNF-α receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2-3 ml of plasma was obtained from each blood sample and stored at -80 °C. RESULTS: The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1. CONCLUSION: Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints.
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Calcitonina/sangre , Neutropenia/sangre , Precursores de Proteínas/sangre , Adulto , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Péptido Relacionado con Gen de Calcitonina , Causas de Muerte , Quimiocina CCL11/sangre , Quimiocina CCL2/sangre , Quimiocina CCL3/sangre , Métodos Epidemiológicos , Femenino , Humanos , Inflamación/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Neutropenia/mortalidad , Estudios Prospectivos , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVE: Neuroinflammatory processes seem to contribute to the degeneration of dopaminergic neurons in Parkinson's disease (PD). Chemokines play a role in the pathogenesis of inflammatory diseases, acting mainly as mediators of leukocyte recruitment to inflammatory sites. The aim of the present study was to compare the serum levels of chemokines between healthy subjects and PD patients and to correlate these levels with the severity of PD. METHODS: We used ELISA to measure the levels of CCL3, CCL11, CCL24, CXCL8 and CXCL10 chemokines in the serum of PD patients (n = 47) and age- and gender-matched controls (n = 23). Patients were also clinically evaluated with the Unified Parkinson's Disease Rating Scale, the Modified Hoehn and Yahr Staging Scale and the Modified Schwab and England Activities of Daily Living Scale. RESULTS: There was no significant difference in serum levels of chemokines between controls and PD patients. There was no correlation between the serum levels of chemokines and the clinical measures of disease severity. CONCLUSIONS: These findings suggest that serum levels of chemokines may not be considered as potential biomarkers of PD.
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Quimiocina CCL11/sangre , Quimiocina CCL24/sangre , Quimiocina CCL3/sangre , Quimiocina CXCL10/sangre , Interleucina-8/sangre , Enfermedad de Parkinson/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/inmunologíaRESUMEN
BACKGROUND/AIMS: Although eosinophils are considered to play an important role in the pathogenesis of various parasitic, allergic and autoimmune digestive diseases, their role in fulminant hepatic failure (FHF) is unknown. Our contribution was to identify and quantify eosinophils and cytokine levels [interleukin (IL)-6, IL-5 and macrophage inflammatory protein (MIP)-1alpha] in liver parenchyma and peripheral blood from FHF patients at pre- and post-transplantation steps. METHODS: Histochemical methods were used to identify/quantify eosinophils in liver samples. Liver and plasma cytokine levels were quantified using immunofluorescence methods. RESULTS: Fulminant hepatic failure patients showed a high number of intrahepatic eosinophils concomitant with an increased expression of IL-6, besides the IL-6-positive eosinophils associated with the lack of IL-5. Also, an increased number of eosinophils and soluble IL-6 and MIP-1alpha with a low expression of IL-5 in peripheral blood at the pretransplantation step was observed. CONCLUSIONS: The increased number of intrahepatic eosinophils, besides the high production of IL-6, may be involved in liver dysfunction. In addition, the low presence of IL-5 in liver and peripheral blood may represent a particular pattern of eosinophil behaviour in human liver failure, which may also involve MIP-1alpha. Further ex vivo studies are necessary to evaluate the specific role of eosinophils in FHF.
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Eosinofilia/sangre , Eosinófilos/inmunología , Interleucina-5/sangre , Interleucina-6/sangre , Fallo Hepático Agudo/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Movimiento Celular , Quimiocina CCL3/sangre , Preescolar , Eosinofilia/fisiopatología , Femenino , Hepatocitos/metabolismo , Humanos , Hígado/metabolismo , Fallo Hepático Agudo/fisiopatología , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Paracoccidioidomycosis (PCM) is the most common systemic mycosis in Latin America. A major problem in the management of PCM is to determine the best time to discontinue therapy due to the high relapse rate among patients. Soluble TNF receptors (sTNF-R) levels and chemokines are associated with disease activity in several infectious, inflammatory and autoimmune disorders. The aim of the present work was to evaluate levels of sTNF-R1, sTNF-R2 and chemokines in serum of patients with adult type of PCM, before and after antifungal therapy, and to correlate those levels to disease activity. Concentrations of sTNF-R1, sTNF-R2 and CXCL9 were higher in untreated patients and decreased progressively with treatment. The serum marker with the best accuracy to discriminate PCM cases from controls was sTNF-R2. sTNF-R1 did not drop to control levels before 36 months of treatment. CCL2 and CCL3 levels were low at baseline in PCM patients, raised significantly after 12 months of treatment and diminished thereafter. CCL24 levels were higher after 36 months of antifungal therapy in PCM patients. CCL11 levels were not statistically different from control subjects. sTNF-R1, sTNF-R2 and CXCL9 may be useful as laboratory parameters to assess disease activity in PCM patients.
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Quimiocina CXCL9/sangre , Paracoccidioidomicosis/inmunología , Paracoccidioidomicosis/patología , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Adulto , Brasil , Quimiocina CCL2/sangre , Quimiocina CCL24 , Quimiocina CCL3/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paracoccidioidomicosis/tratamiento farmacológico , Suero/químicaRESUMEN
Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.