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BACKGROUND & AIMS: Several studies have suggested that increased intake of saturated fatty acids (SFAs) may have a pro-inflammatory effect, potentially impacting muscle mass and strength. However, the relationship of plasma SFAs and their subtypes (which reflect dietary SFA intake) with muscle mass and strength remains poorly understood. This study aimed to evaluate the association of plasma SFAs with lean mass and handgrip strength in adults. METHODS: A cross-sectional study was conducted with 896 participants aged 20-59 years, selected from a subsample of the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Total plasma SFAs and their subtypes were detected using gas chromatography-mass spectrometry. Lean mass was assessed using dual-energy X-ray absorptiometry, with evaluations of both total lean mass and appendicular lean mass. Muscle strength was measured using a handgrip dynamometer, with combined grip strength calculated by summing the highest values from each hand. Linear regression analysis was conducted to examine the association between plasma SFAs, lean mass, and handgrip strength, adjusting for potential confounders. RESULTS: Total lean mass was negatively associated with total plasma SFAs and several of their subtypes such as plasma levels of stearic acid, palmitic acid, arachidic acid, tricosanoic acid, lignoceric acid, and docosanoic acid. Similarly, appendicular lean mass was negatively associated with total plasma SFAs, as well as with several specific subtypes, including palmitic acid, stearic acid, margaric acid, pentadecanoic acid, and myristic acid. Handgrip strength also demonstrated a negative association with total plasma SFAs, including specific subtypes such as lauric acid, palmitic acid, capric acid, margaric acid, pentadecanoic acid, and myristic acid. CONCLUSION: Total plasma SFAs and several of their subtypes are inversely associated with lean mass and muscle strength in adults.
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Ácidos Graxos , Força da Mão , Inquéritos Nutricionais , Humanos , Adulto , Masculino , Feminino , Ácidos Graxos/sangue , Pessoa de Meia-Idade , Estudos Transversais , Adulto Jovem , Absorciometria de Fóton , Ácido Palmítico/sangue , Composição Corporal , Ácidos Esteáricos/sangue , Força Muscular , Músculo EsqueléticoRESUMO
PURPOSE: The present study aims to describe initial changes in muscle thickness and composition, muscle growth signaling mediators, and systemic inflammation in critically ill patients after major trauma. METHODS: This observational study was carried out in a Level-I nonprofit trauma center. Thirty adults requiring mechanical ventilation were assessed within 24 h post-admission. Skeletal muscle wasting was evaluated using ultrasound for muscle thickness and echogenicity along with circulating insulin-like growth factor 1 (IGF-1) and inflammatory cytokines over five consecutive days. Changes over time were assessed using ANOVA repeated-measures analysis with a Bonferroni post-hoc test. Bivariate correlations were evaluated using Pearson or Spearman coefficients. RESULTS: Over five days, a significant decrease (11%) in rectus femoris thickness (3.91 ± 0.86 to 3.47 ± 0.64, cm, p = 0.01) and an increase (29%) in echogenicity (62.1 ± 13.1 to 80.4 ± 17.3, AU, p < 0.01) were observed among the 30 patients included in this study. Circulating levels of IGF-1 exhibited a 38% reduction (68.8 ± 43.6 to 42.4 ± 29.4, ng/mL, p = 0.01). Furthermore, pro-inflammatory cytokine (IFN-y) increased by 17% (4.83 ± 1.39 to 5.66 ± 1.61, pg./mL, p = 0.02) from day 1 to day 5. CONCLUSIONS: These findings reveal substantial thickness and muscle composition alterations within 48 h post-admission, worsening over five days. Despite standard rehabilitation care, changes in IGF-1 and IFN-y levels suggest early declines in muscle growth stimulus and increased inflammation.
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Estado Terminal , Fator de Crescimento Insulin-Like I , Atrofia Muscular , Ultrassonografia , Humanos , Masculino , Feminino , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/etiologia , Adulto , Pessoa de Meia-Idade , Fator de Crescimento Insulin-Like I/metabolismo , Ferimentos e Lesões/diagnóstico por imagem , Ferimentos e Lesões/complicações , Diagnóstico Precoce , Citocinas/sangue , Mediadores da Inflamação/sangue , Músculo Esquelético/diagnóstico por imagem , Respiração Artificial , Centros de Traumatologia , Inflamação/diagnóstico por imagemRESUMO
Toxoplasma gondii is a protozoan parasite causing toxoplasmosis, a principal concern for public health and livestock industries. Effective vaccination strategies are crucial for controlling toxoplasmosis, particularly in the lamb, which are significant reservoirs of T. gondii. In addition, ovine toxoplasmosis also causes economic losses due to abortions and reproductive complications. In this study, we evaluated two immunization strategies to elucidate the immune protective potential of T. gondi major surface protein SAG1 fused to the plant heat shock proteins 90-kDa (pHsp90) adjuvant against experimental toxoplasmosis in lambs. We performed an oral administration of fresh leaves homogenate infiltrated with a B- and T-cell antigenic epitope-containing surface protein SAG1 (SAG1HC) fused to Arabidopsis thaliana Hsp90 (AtHsp81.2-SAG1HC) (Plant Vaccine) and a subcutaneous administration of recombinant SAG1HC fused to Nicotiana benthamiana Hsp90 (NbHsp90.3-SAG1HC) produced in Escherichia coli (Recombinant Vaccine). Our results showed that only the Recombinant Vaccine significantly increased anti-rSAG1 total IgG values (⼠4-fold more than the Vehicle and Control groups). In addition, only lambs immunized with the Plant Vaccine showed a significant increase (⼠3-fold more than the Vehicle and Control groups) in IFN-γ serum levels after the experimental infection (evaluated 8 days post-challenge). On the other hand, we also observed a statistically significant decrease (⼠80 % less) in histopathological lesions (injury score) in challenged vaccinated lambs compared to challenged but not vaccinated animals (Vehicle and Control groups). Previously, we showed that the chimera recombinant Gra4-Gra7 protein is an acute marker of human infection. Since Gra4-Gra7 is not connected to the SAG1 immunogen, this chimera allows us to monitor infection in challenged lambs early. All lambs from the Control and Vehicle groups showed higher rates of serological reactivity than lambs from the vaccinated groups, concurrently with increased severity of lesions. These results suggest that the Plant-based and Recombinant Vaccines are promising candidates for controlling T. gondii infection in lambs, with potential benefits for enhancing public health and animal welfare.
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Anticorpos Antiprotozoários , Antígenos de Protozoários , Proteínas de Choque Térmico HSP90 , Nicotiana , Proteínas de Protozoários , Vacinas Protozoárias , Doenças dos Ovinos , Toxoplasma , Toxoplasmose Animal , Animais , Ovinos , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Toxoplasma/imunologia , Toxoplasma/genética , Toxoplasmose Animal/prevenção & controle , Toxoplasmose Animal/imunologia , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/genética , Anticorpos Antiprotozoários/sangue , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/imunologia , Proteínas de Choque Térmico HSP90/imunologia , Proteínas de Choque Térmico HSP90/genética , Vacinas Protozoárias/imunologia , Vacinas Protozoárias/administração & dosagem , Vacinas Protozoárias/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Imunoglobulina G/sangue , Plantas Geneticamente Modificadas , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , ImunizaçãoRESUMO
BACKGROUND: Gestational diabetes is one of the most prevalent diseases in pregnancy, with an incidence of 5 to 18% in Brazil, and is associated with high morbidity rates. The first-line treatment is insulin, although some recent studies have indicated that metformin might also be effective. Metformin is safe in pregnancy and appears to produce better results than insulin, including reduced gestational weight gain (GWG) and smaller gestational-age newborns. Few studies have been conducted on this topic in low- and middle-income countries. METHODS: We designed an open randomized controlled trial comparing two treatments for pregnant women with type II diabetes mellitus (DM) and gestational diabetes (DMG): the metformin group (intervention) and the insulin group (as a routine service). The primary outcome is glycemic control. The secondary outcomes are GWG, the occurrence of hypertensive syndromes, macrosomia, and neonatal hypoglycemia. The sample will comprise 92 pregnant women, 46 per group. The inclusion criteria will be GDM or type II DM requiring medication for glycemic control, singleton pregnancy, and gestational age under 34 weeks. The exclusion criteria will be current treatment with any medication for glycemic control, type I DM, and intolerance to the study medications (metformin or insulin). Women will be routinely followed during antenatal care, childbirth, and the postpartum period. Statistical analyses will include the intention-to-treat approach and a comparison between the two groups. DISCUSSION: Considering the Brazilian socioeconomic reality and the safety of metformin demonstrated in previous trials, we expect that the MevIP study will demonstrate that metformin is an adequate and appropriate medication for GDM treatment in the Brazilian population, representing an alternative to insulin for GDM. TRIAL REGISTRATION: This protocol has been registered prospectively in ReBEC under the ID RBR-3j3cktx in August 11, 2023.
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Glicemia , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Controle Glicêmico , Hipoglicemiantes , Insulina , Metformina , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Gravidez , Metformina/uso terapêutico , Metformina/efeitos adversos , Feminino , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Insulina/uso terapêutico , Insulina/efeitos adversos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Controle Glicêmico/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Brasil , Ganho de Peso na Gestação , Resultado do Tratamento , AdultoRESUMO
Hepatitis B virus surface antigen (HBsAg), IgM and IgG antibodies to hepatitis B virus core antigen (anti-HBcIgM and anti-HBcIgG) comprise serological markers of hepatitis B virus (HBV) infection of great importance in the epidemiological surveillance of hepatitis B, since they have been routinely considered for classifying the acute and chronic clinical forms of HBV infection. This classification is established according to the expression and dynamics of these markers in the infected person's bloodstream, which serves as the basis for the differential diagnosis between the two clinical entities. However, in certain circumstances, both acute and chronic infection, the detection of these markers may not occur in the bloodstream, favoring the occurrence of atypical serological profiles of infection, and compromising the correct infection clinical classification. In addition, the complex and varied nature of hepatitis B serological profiles may compromise the health professional's ability to analyze the case and, thus, correctly classify the infection's clinical form. Since the expression of these markers in the bloodstream occurs dynamically, with consequent changes in the patient's serological profile as he progresses towards recovery or chronicity, the diagnosis of acute or chronic infection may also be compromised, if it is established based on the collection of a single sample and without knowing the patient's clinical history and their epidemiological antecedents. This manuscript addresses the sensitivity and specificity of HBsAg, anti-HBcIgM, and anti-HBcIgG serological markers detection in the clinical classification of HBV infection and in the epidemiological surveillance of hepatitis B. This review is covering the clinical and epidemiological interpretations of the markers in and of themselves, not in reference to any specific assays.
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Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B , Imunoglobulina G , Imunoglobulina M , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Hepatite B/epidemiologia , Hepatite B/imunologia , Hepatite B/diagnóstico , Hepatite B/sangue , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Biomarcadores/sangue , Monitoramento EpidemiológicoRESUMO
BACKGROUND: Serum cardiac troponin (cTn) elevation is a well-established phenomenon in sepsis. However, the clinical significance of this phenomenon with high-sensitivity (hs) assays and the current sepsis definition needs to be settled. RESEARCH QUESTION: What is the association between early serum cTn levels measured by hs-assays and the risk of short-term mortality in septic patients? STUDY DESIGN AND METHODS: We conducted a systematic review using a comprehensive PubMed, Scopus, and Embase search. Studies were eligible if they reported association data on early hs-cTn and mortality in an adult sample with sepsis that met the Sepsis-3 definition. For the synthesis of the effect of hs-cTn on mortality, we applied random effect models on the pooled unadjusted and adjusted odds ratio (OR and aOR, respectively) of elevated vs. normal hs-cTn serum values, and on the crude standardized mean difference (SMD) of hs-cTn between survivors and non-survivors. RESULTS: In total, 6242 patients from 17 studies were included, with short-term mortality rates ranging from 16.9% to 53.8%. Using a crude analysis, non-survivor patients showed higher hs-cTn than survivors (SMD of 0.87, 95%CI: 0.41-1.33). Elevated hs-cTn was associated with increased mortality (OR = 1.78, 95% CI: 1.41-2.25). However, this prognostic effect was absent in studies that adjusted for different confounders (aOR = 1.06, 95% CI: 0.99-1.14). DISCUSSION AND CONCLUSIONS: Non-survivors of sepsis exhibited significantly elevated hs-cTn levels. While elevated hs-cTn levels are associated with an increased risk of mortality, they are not independently associated with this outcome in sepsis.
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Biomarcadores , Sepse , Humanos , Sepse/mortalidade , Sepse/sangue , Biomarcadores/sangue , Troponina/sangue , Troponina/análiseRESUMO
The unprecedented worldwide pandemic caused by COVID-19 has motivated several research groups to develop machine-learning based approaches that aim to automate the diagnosis or screening of COVID-19, in large-scale. The gold standard for COVID-19 detection, quantitative-Real-Time-Polymerase-Chain-Reaction (qRT-PCR), is expensive and time-consuming. Alternatively, haematology-based detections were fast and near-accurate, although those were less explored. The external-validity of the haematology-based COVID-19-predictions on diverse populations are yet to be fully investigated. Here we report external-validity of machine learning-based prediction scores from haematological parameters recorded in different hospitals of Brazil, Italy, and Western Europe (raw sample size, 195554). The XGBoost classifier performed consistently better (out of seven ML classifiers) on all the datasets. The working models include a set of either four or fourteen haematological parameters. The internal performances of the XGBoost models (AUC scores range from 84% to 97%) were superior to ML models reported in the literature for some of these datasets (AUC scores range from 84% to 87%). The meta-validation on the external performances revealed the reliability of the performance (AUC score 86%) along with good accuracy of the probabilistic prediction (Brier score 14%), particularly when the model was trained and tested on fourteen haematological parameters from the same country (Brazil). The external performance was reduced when the model was trained on datasets from Italy and tested on Brazil (AUC score 69%) and Western Europe (AUC score 65%); presumably affected by factors, like, ethnicity, phenotype, immunity, reference ranges, across the populations. The state-of-the-art in the present study is the development of a COVID-19 prediction tool that is reliable and parsimonious, using a fewer number of hematological features, in comparison to the earlier study with meta-validation, based on sufficient sample size (n = 195554). Thus, current models can be applied at other demographic locations, preferably, with prior training of the model on the same population. Availability: https://covipred.bits-hyderabad.ac.in/home; https://github.com/debashreebanerjee/CoviPred.
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COVID-19 , Aprendizado de Máquina , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/sangue , COVID-19/diagnóstico , Itália/epidemiologia , Brasil/epidemiologia , Europa (Continente)/epidemiologia , SARS-CoV-2/isolamento & purificação , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Metabolomics is an analytical approach utilized to explore the metabolic profiles of biological systems. This process typically involves the application of techniques such as nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). In the case of schistosomiasis, metabolomics has been employed to identify potential diagnostic biomarkers, examine the host's metabolic response, and explore more effective therapeutic strategies. The objective of this scoping review is to assess the scope and characteristics of metabolomic research on schistosomiasis conducted over the past decade. METHODS: To identify relevant original publications, a systematic search was conducted in the PubMed and Web of Science databases using the following search terms: ("Metabolomics" OR "Metabolomic" OR "Metabonomics" OR "Metabonomic") AND ("Schistosomiasis" OR "Schistosoma"). These terms were applied to the titles and abstracts of the publications, with a focus on the period from January 2014 to December 2024. RESULTS: The initial search yielded 48 articles. However, after a thorough evaluation of the abstracts, 14 articles were selected based on the established inclusion criteria. The selection process is visually depicted in the PRISMA flowchart. The majority of the studies included in this review were conducted in China (7 articles) and Brazil (3 articles). Approximately two-thirds of the studies utilized animal models, with serum serving as biofluid in 66% of the studies. The findings of this scoping review suggest that chromatographic techniques coupled with mass spectrometry are predominantly used in metabolomic research on schistosomiasis, accounting for 75% of the studies. The identified metabolites are associated with metabolic pathways related to glycolysis, the TCA cycle, and amino acid metabolism, as well as demonstrating alterations resulting from intestinal dysbiosis observed during the infection. As exemplified by succinate and citrate, which are present in the alterations of energy pathways in Schistosoma mansoni and Schistosoma japonicum species. The serum levels of these metabolites are modified, reflecting the host's metabolic and immunological responses induced by the infections. CONCLUSIONS: These studies successfully elucidated the metabolic pathways and key metabolites involved in schistosomiasis. The findings are significant for the future identification of diagnostic biomarkers and the development of novel antiparasitic agents targeting Schistosoma species. CLINICAL TRIAL: Not Applicable.
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Biomarcadores , Metabolômica , Esquistossomose , Metabolômica/métodos , Esquistossomose/metabolismo , Humanos , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Schistosoma/metabolismo , Espectrometria de Massas/métodos , Espectroscopia de Ressonância Magnética/métodosRESUMO
BACKGROUND: Anti-PM/Scl autoantibody has been associated with an overlap between polymyositis (PM) and systemic sclerosis (SSc). However, due to limited studies, the relevance of this autoantibody in patients with idiopathic inflammatory myopathies (IIMs) without SSc was analyzed. METHODS: This single-center retrospective cohort study was conducted between 2004 and 2024. A total of 93 adult patients with IIMs (66 with dermatomyositis and 27 with PM - EULAR/ACR 2017) without SSc were included: 16 anti-PM/Scl(+) and 77 anti-PM/Scl(-). Patients with other types of IIMs, cancer-associated myositis, or overlap myositis, including SSc, as well as those with other myositis-specific and/or myositis-associated autoantibodies were excluded. RESULTS: The median age, sex distribution, and median follow-up duration were comparable between the anti-PM/Scl(+) and anti-PM/Scl(-) groups. There were no differences in clinical and laboratory characteristics, except for a higher frequency of lung involvement, joint involvement, "mechanics' hand," "hiker's feet," and Raynaud's phenomenon, in contrast to a lower frequency of facial rash and "V"-neck sign in patients with anti-PM/Scl(+) than in those with anti-PM/Scl(-) (all P < 0.05). Furthermore, patients with anti-PM/Scl(+) exhibited a higher frequency of disease relapse (68.8% vs. 33.8%), disease activity (50.0% vs. 24.7%), and immunosuppressant use (methotrexate or azathioprine) at the last medical evaluation (all P < 0.05). Severe infection and death rates were comparable between the groups. CONCLUSIONS: Anti-PM/Scl positivity was observed in 17.2% of the sample analyzed in the present study. Patients with this autoantibody present clinical manifestations resembling anti-synthetase syndrome, with increased disease relapse and activity rates.
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Autoanticorpos , Miosite , Humanos , Miosite/imunologia , Miosite/sangue , Feminino , Masculino , Estudos Retrospectivos , Autoanticorpos/sangue , Pessoa de Meia-Idade , Adulto , Dermatomiosite/imunologia , Dermatomiosite/sangue , Polimiosite/imunologia , Complexo Multienzimático de Ribonucleases do Exossomo/imunologia , Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Estudos de Coortes , Idoso , Proteínas de Ligação a DNA/imunologia , Exorribonucleases , Complexo Mi-2 de Remodelação de Nucleossomo e DesacetilaseRESUMO
PURPOSE: To identify the prognostic variables related to the survival of patients operated on for adenocarcinoma of the rectum who underwent preoperative radiochemotherapy (RCT). METHODS: We studied 70 patients from the Discipline of Surgical Gastroenterology at Escola Paulista de Medicina from 2000 to 2019, with rectal cancer located up to 10 cm from the anal verge and with stages II or III, submitted to preoperative RCT and curative surgery (R0) and with follow-up of at least 12 months. Clinical restaging was performed four to six weeks after the end of neoadjuvant treatment to characterize the degree of clinical tumor regression. Surgery by laparotomy or videolaparoscopy was performed six to 12 weeks after RCT. Primary endpoint were: overall survival (OS), disease-free survival (DFS), metastasis-free survival (MSS), and neoplasm-specific survival (SEN). These were compared with gender, age, carcinoembryonic antigen (CEA) dosage, distance from the tumor to the anal verge, radiation dose, radiotherapy-surgery interval, clinical regression, type of surgery, pT and pN TNM stage tumor, number of nodes, circumferential resection margin, and complete pathological response. Survival was assessed by Kaplan-Meier curves. Univariate and multivariate Cox analyses were calculated to identify factors associated with survival outcomes. RESULTS: The mean follow-up time was 62 months. The pathological complete response rate was 18.6%. Univariate cox regression showed a significant relationship of CEA equal to or greater than 4 ng/mL with DFS and MFS, pT3/pT4 staging with DFS, MFS and SEN, pN1/N2 with DFS, MFS and SEN and stages II and III with DFS and MFS. Multivariate regression found that CEA, pT, and pN staging are independent prognostic factors for DFS, MFS, and SEN. CONCLUSION: Carcinoembryonic antigen level prior to radiotherapy, pT staging and pN staging were independent prognostic factors for survival in patients with rectal adenocarcinoma who are treated with preoperative radiochemotherapy.
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Adenocarcinoma , Quimiorradioterapia , Estadiamento de Neoplasias , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Masculino , Adenocarcinoma/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Quimiorradioterapia/métodos , Adulto , Terapia Neoadjuvante/métodos , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Resultado do Tratamento , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/análise , Cuidados Pré-Operatórios/métodosRESUMO
Capillary blood collection presents advantages such as reduced invasiveness over venous serum for syphilis diagnosing. This study aimed to compare diagnostic accuracy between capillary and venous blood samples for syphilis diagnosis. Individuals aged ≥ 18 years were included in a cross-sectional study. Syphilis screening was done using Rapid tests (RT) followed by collection of serum capillary and venous samples for VDRL and TPHA test. Sensitivity, specificity, and Kappa coefficient were calculated. Of 191 participants, 115 RT + and 76 RT-. Diagnostic properties did not significantly differ between capillary and venous samples. Capillary VDRL showed 99% sensitivity and 100% specificity, mirroring TPHA results. Furthermore, there was significant agreement between sample types for both serological tests (p < 0.001). Capillary sampling offers comparable diagnostic accuracy to venous collection, regardless of serum quality. Capillary sampling holds promise, particularly in developing countries and large-scale testing initiatives.
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Coleta de Amostras Sanguíneas , Capilares , Sensibilidade e Especificidade , Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/sangue , Masculino , Adulto , Feminino , Estudos Transversais , Coleta de Amostras Sanguíneas/métodos , Pessoa de Meia-Idade , Sorodiagnóstico da Sífilis/métodos , Treponema pallidum , Adulto JovemRESUMO
OBJECTIVES: To evaluate the effectiveness of 18 different host biomarkers in differentiating bacterial from non-bacterial acute febrile illness (AFI) in resource-limited settings, specifically in Brazil, Malawi and Gabon. DESIGN: Multinational, cross-sectional study. SETTING: The study was carried out across multiple primary healthcare facilities, including urban and rural settings, with a total of three participating centres. Recruitment took place from October 2018 to July 2019 in Brazil, May to November 2019 in Gabon and April 2017 to April 2018 in Malawi. PARTICIPANTS: A total of 1915 participants, including children and adults aged 21-65 years with a fever of≤7 days, were recruited through convenience sampling from outpatient clinics in Brazil, Gabon and Malawi. Individuals with signs of severe illness were excluded. Written consent was obtained from all participants or their guardians. INTERVENTION: This is not applicable as the study primarily focused on biomarker evaluation without specific therapeutic interventions. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the ability of each host biomarker to differentiate between bacterial and non-bacterial AFI, as evaluated by area under the receiver operating characteristic (AUROC) curves. Secondary outcomes included the performance of individual biomarkers across the different study sites and in a multivariable setting. RESULTS: A Kruskal-Wallis test, adjusted by Benjamini-Hochberg, was performed for each biomarker to identify covariates with a significant difference in the distribution of biomarker values. The analysis revealed that country of origin (Brazil, Gabon, Malawi), age, sex and malaria status significantly impacted biomarker distribution (p≤0.001). The most widely known biomarkers, such as white blood cell (WBC) count and C-reactive protein (CRP), demonstrated the best performance in distinguishing between bacterial and non-bacterial infections, with AUROCs reaching up to 0.83 (0.77-0.88) for WBC count and 0.71 (0.59-0.82) for CRP. However, none of the evaluated novel host biomarkers exhibited high performance (AUROC<0.70 in most cases) and variations in biomarker performance were observed across the three settings. Multivariable analyses demonstrated that while the best combination of biomarkers achieved higher AUROCs, the increase was modest (1-13%), suggesting that the interaction of biomarkers contributed minimally to predictive accuracy. CONCLUSIONS: There is a continued need for innovation in the host-biomarker space as the available markers do not meet the needs of diverse populations around the globe. This highlights the importance of targeted evaluations in non-severe patients in multiple settings to understand the true potential for real-life use. The findings highlight that not one-marker fits all settings and novel innovations remain urgently needed. TRIAL REGISTRATION NUMBER: Clinical trial number: NCT03047642.
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Antibacterianos , Infecções Bacterianas , Biomarcadores , Febre , Humanos , Estudos Transversais , Biomarcadores/sangue , Masculino , Feminino , Adulto , Malaui , Pessoa de Meia-Idade , Febre/diagnóstico , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/sangue , Brasil , Idoso , Adulto Jovem , Gabão , Curva ROC , Doença AgudaRESUMO
Crohn's disease (CD) involves immune system interactions with intestinal tissue, driven by pro-inflammatory cytokines like Tumor Necrosis Factor (TNF-α). Adalimumab, targeting TNF-α, regulates associated inflammatory responses. Despite being humanized, it may induce immunogenic processes, affecting treatment effectiveness. Thus, monitoring serum adalimumab and anti-drug antibody (ADA) levels can optimize therapy. Understanding genetic factors influencing adalimumab response can enhance personalized treatment and improve patient quality of life. We aimed to quantify adalimumab serum levels, assess test interchangeability, detect ADA, examine immune complex formation, and investigate genetic phenotypes related to immunogenicity in CD patients. Seventy CD patients in the maintenance phase with adalimumab were classified into active (CDA) and remission (CDR) groups. Adalimumab concentration was determined via enzyme-linked immunosorbent assay (ELISA-Promonitor) and lateral flow assay (Quantum Blue), with assay interchangeability assessed statistically. ADA and immune complex formation were quantified using ELISA assays. DNA was genotyped for the genes ATG16L1, CD96, and CD155. No significant differences in adalimumab serum concentrations were observed between groups, regardless of the assay. However, a statistical difference between the tests indicated measurement disparity (P = 0.003), with moderate agreement (Lin's correlation of 0.247). ADA was detected in 4 of 27 of the patients with infratherapeutic levels, 3 in the CDA group and 1 in the CDR group. Analysis of immune complexes revealed significantly higher concentrations in the CDA group (P = 0.0125). The genotypic evaluation revealed significant associations for the CD96 CC (wild-type) genotype with higher CRP levels, colonic involvement, and infratherapeutic levels of adalimumab. ATG16L1 CC genotype was associated with higher CDEIS and fecal calprotectin values, while the variant (TT) genotype had lower platelet counts. The effectiveness of treatment with adalimumab was not directly related to higher medication levels in this cohort. The disparity between tests indicates the need to use only one test in patient follow-up to ensure accuracy in therapeutic monitoring. Genotypic differences highlight the correlation between the wild genotype for CD96 and ATG16L1 with unfavorable laboratory and endoscopic response to adalimumab. Finally, the more significant levels of immune complexes in the CDA group indicate an association with a worse response to adalimumab.
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Adalimumab , Doença de Crohn , Monitoramento de Medicamentos , Humanos , Adalimumab/uso terapêutico , Adalimumab/sangue , Adalimumab/imunologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/sangue , Monitoramento de Medicamentos/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/sangue , Anti-Inflamatórios/farmacocinética , Genótipo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Imunogenética/métodos , Proteínas Relacionadas à AutofagiaRESUMO
INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrinopathy in women of reproductive age. MicroRNA (miRNAs) are small non-coding RNAs related to the control of gene expression in biological fluids. Our study analyzed the expression of miRNAs related to inflammation in individuals with PCOS compared to controls. METHODS: Twenty patients with PCOS and 20 controls, matched by body mass index and age, were included in the study. The miRNAs evaluated were miRNA-30c-5p; miRNA-545-3p and miRNA-125a-5p. RESULTS: The expression of the miRNAs was similar between the two groups. A positive correlation was observed between the expression of miRNA-125a-5p and LDLc levels only in the PCOS group. Subsequent analysis of biological pathways showed that miRNA-125a -5p is significantly involved in the regulation of SREBP/SREBF pathways of cholesterol biosynthesis, glycolysis, insulin receptor signaling, oxidative stress-induced senescence and estrogen-dependent gene expression. CONCLUSION: The results suggest that the miRNA-125a-5p shows a potential implication to the regulation of lipid biosynthesis and LDL-c levels in PCOS women.
Assuntos
Regulação da Expressão Gênica , MicroRNAs , Síndrome do Ovário Policístico , Transdução de Sinais , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Estudos de Casos e Controles , Adulto , Transdução de Sinais/genética , LDL-Colesterol/sangueRESUMO
Several studies have related reactive temperament to poorer productive and reproductive performance in cattle. However, no studies have aimed to investigate the effect of temperament on sexual development and precocity of male cattle. The objective of this study was to test the hypothesis that reactive animals exhibit delayed sexual development and poorer reproductive performance. For the study, 40 crossbred male cattle (Nellore x Santa Gertrudis) at 12 months were selected. The animals underwent behavioral evaluation and were divided into two groups: calm (CA; nâ¯=â¯24) and reactive (RE; nâ¯=â¯16). All steers were weighed to monitor weight gain, and blood samples were collected to measure cortisol and testosterone concentrations. Semen collections by electroejaculation were performed to determine the onset of puberty and assess sperm quality. Cryopreservation tests were conducted, and the samples were evaluated for kinetics and plasma membrane integrity. Ultrasound examinations assessed testicular development. Additionally, testicular biopsies were performed to evaluate spermatid and spermatozoa ratios. There was a trend toward higher cortisol production (Pâ¯=â¯0.07) in RE animals. Higher total (Pâ¯=â¯0.03), average (Pâ¯=â¯0.07), and daily (Pâ¯=â¯0.06) weight gains were observed for CA animals. RE steers produced a higher proportion of cells with minor sperm defects (Pâ¯=â¯0.06). Greater vesicular glands development was observed in CA animals (Pâ¯=â¯0.01). No effect of temperament was observed on sexual precocity, cryotolerance, or testosterone production. It was concluded that although temperament does not influence age at puberty, reactive bulls exhibit poorer performance in body development, vesicular glands development, and fresh semen quality compared to calm bulls.
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Temperamento , Animais , Masculino , Bovinos/fisiologia , Temperamento/fisiologia , Análise do Sêmen/veterinária , Maturidade Sexual/fisiologia , Testosterona/sangue , Comportamento Animal/fisiologia , Hidrocortisona/sangue , Reprodução/fisiologia , Testículo/fisiologiaRESUMO
SARS-CoV-2 emerged rapidly as a pandemic, leading to the urgent development and authorization for the use of several vaccines, with questions relating to immunogenicity in previously infected people or to virus variants. As such, we sought to determine the humoral and cellular immune response of healthy adults to distinct SARS-CoV-2 variants upon AZD1222/COVISHIELD vaccination, using chemiluminescence (CMIA), neutralizing antibody (PRNT) and analysis of activation-induced marker (AIM) by flow cytometry, respectively. We enrolled 75 volunteers, including 26 individuals previously infected with SARS-CoV-2. Our findings demonstrated that AZD1222 vaccine induced increased levels of SARS-CoV-2-specific antibodies after two-dose vaccination scheme, as detected by CMIA (mean = 49 BAU/mL to 743 BAU/mL) and PRNT (GMT = 3, 95 % CI 2-4, to 19, 11-34). After vaccination, all volunteers presented detectable antibodies by CMIA while only 64 % presented positive PRNT. Seroconversion rates were 91 % and 48 % by CMIA and 59 % by PRNT after the first and second dose, respectively. The PRNT to Delta variant demonstrated lower titers as compared to Wuhan-like and a seroconversion of 57 %. Although by CMIA all volunteers were classified as high responders, some volunteers showed no response by PRNT and AIM. In general, previously infected volunteers had higher post-vaccination antibody titers after each dose. CD4+ T cell response was generally higher than CD8+ T cells for all variants. Overall, we observed that AZD1222 vaccination induced cross-reactivity to SARS-CoV-2 variants, in both cellular and humoral responses. During volunteer follow-up, we observed that the elevated antibody titers are lasting and were incremented by the first booster. In conclusion, our findings showed that AZD1222 vaccine was able to induce a robust immune response upon primary immunization, with cross-reactivity for the Delta VOC.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Imunidade Humoral , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , Adulto , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Masculino , Feminino , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Vacinação/métodos , Voluntários Saudáveis , Imunogenicidade da VacinaRESUMO
The diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests. In this context, the identification of more refined antigens could contribute to improve the diagnostic quality, as well as the employ of less invasive biological samples. In this study, the eukaryotic initiation factor 5a (eIF5A) protein, one specific B-cell epitope predicted in the protein sequence, and a parasite antigenic preparation (SLA) were evaluated as antigens in ELISA experiments, which were reacted against paired serum and urine samples from 170 patients. ROC curves were constructed with the individual OD values and, when serum was used as analyte, eIF5a, peptide and SLA showed sensitivity of 44.0 %, 29.3 % and 29.3 %, respectively, and specificity of 100 %, 99.0 %, and 96.0 %, respectively PPV, NPV and Youden index for reIF5a were 100 %, 52.0 % and 0.44, respectively; while for peptide were of 98.0 %, 46.5 %, and 0.28, respectively; and for SLA, they were of 92.0 %, 46.0 %, and 0.26, respectively. Using urine as biological sample; eIF5a, peptide and SLA showed sensitivity of 100 %, 48.0 % and 52.0 %, respectively, and specificity of 99.1 %, 98.9 %, and 89.0 %, respectively. PPV, NPV and Youden index values for reIF5a were of 99.3 %, 100 % and 0.99, respectively; while for peptide were of 99.1 %, 54.3 %, and 0.47, respectively; and for SLA, they were of 88.0 %, 53.5 %, and 0.41, respectively. A preliminary assay using paired samples collected before and after treatment of eight patients showed a significant reduction in IgG levels when the three antigens were tested, with highest reductions found when urine was used as analyte. In this context, data suggest the use of patient urine as an alternative biological analyte for the diagnosis of TL.
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Anticorpos Antiprotozoários , Antígenos de Protozoários , Ensaio de Imunoadsorção Enzimática , Leishmaniose Cutânea , Sensibilidade e Especificidade , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Antígenos de Protozoários/urina , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/sangue , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/urina , Leishmaniose Cutânea/imunologia , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/urina , Anticorpos Antiprotozoários/imunologia , Fatores de Iniciação de Peptídeos/urina , Fatores de Iniciação de Peptídeos/imunologia , Fator de Iniciação de Tradução Eucariótico 5A , Curva ROC , Epitopos de Linfócito B/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Soro/imunologia , Soro/química , Urina/químicaRESUMO
INTRODUCTION: Inflammation is hypothesized to be a pivotal factor influencing muscle function, with C-Reactive Protein (CRP) serving as a common biomarker of inflammation. However, the literature pertaining to the relationship between CRP and muscle mass remains scant, particularly among representative adult populations in the United States. The present study aimed to delve into the association between serum CRP levels and muscle mass among American adults, leveraging data from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2006. METHODS: A cohort of 13,518 participants, representative of the US adult population, underwent dual-energy X-Ray Absorptiometry (DXA) to assess Appendicular Skeletal Muscle Mass (ASM) and had their CRP levels measured. Muscle mass was defined using ASM adjusted by Body Mass Index (ASM/BMI) criteria. Employing weighted logistic regression models, restricted cubic spline analysis, and subgroup analyses, the authors examined the association between serum CRP and low muscle mass. RESULTS: After meticulously adjusting for various covariates, the present findings revealed a positive association between serum CRP levels and the risk of low muscle mass in American adults (OR = 1.07, 95 % CI 1.01â1.14, p = 0.016). Notably, an inverse J-shaped relationship was observed, with serum CRP inflection points of 0.273 mg/dL for the overall population, 0.172 mg/dL for males, and 0.296 mg/dL for females. Subgroup analysis further demonstrated that factors such as gender, race, educational level, smoking status, congestive heart failure, stroke, renal weakness/failure, coronary heart disease, diabetes, hypertension, vigorous physical activity, moderate physical activity, and muscle strengthening activities did not significantly impact this positive correlation (all p for interaction values > 0.05). CONCLUSIONS: This nationally representative cross-sectional study provides robust evidence of an inverse J-shaped association between serum CRP levels and the risk of low muscle mass in adults in the United States, with a critical inflection point of 0.273 mg/dL. These findings may inform future research and clinical strategies aimed at mitigating the negative effects of inflammation on muscle mass and function in the adult population.
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Absorciometria de Fóton , Biomarcadores , Proteína C-Reativa , Músculo Esquelético , Inquéritos Nutricionais , Humanos , Proteína C-Reativa/análise , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estados Unidos , Músculo Esquelético/anatomia & histologia , Biomarcadores/sangue , Índice de Massa Corporal , Estudos Transversais , Sarcopenia/sangue , Idoso , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Although emergency Percutaneous Coronary Intervention (PCI) has been shown to reduce mortality in patients with Acute Myocardial Infarction (AMI), the risk of in-hospital death remains high. In this study, the authors aimed to identify risk factors associated with in-hospital mortality in AMI patients who underwent PCI, develop a nomogram prediction model, and evaluate its effectiveness. METHODS: The authors retrospectively analyzed data from 1260 patients who underwent emergency PCI at Dongyang People's Hospital between June 1, 2013, and December 31, 2021. Patients were divided into two groups based on in-hospital mortality: the death group (n = 61) and the survival group (n = 1199). Clinical data between the two groups were compared. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select non-zero coefficients of predictive factors. Multivariable logistic regression analysis was then performed to identify independent risk factors for in-hospital mortality in AMI patients after emergency PCI. A nomogram model for predicting the risk of in-hospital mortality in AMI patients after PCI was constructed, and its predictive performance was evaluated using the c-index. Internal validation was performed using the bootstrap method with 1000 resamples. The Hosmer-Lemeshow test was used to assess the goodness of fit, and a calibration curve was plotted to evaluate the model's calibration. RESULTS: LASSO regression identified d-dimer, B-type natriuretic peptide, white blood cell count, heart rate, aspartate aminotransferase, systolic blood pressure, and the presence of postoperative respiratory failure as important predictive factors for in-hospital mortality in AMI patients after PCI. Multivariable logistic regression analysis showed that d-dimer, B-type natriuretic peptide, white blood cell count, systolic blood pressure, and the presence of postoperative respiratory failure were independent factors for in-hospital mortality. A nomogram model for predicting the risk of in-hospital mortality in AMI patients after PCI was constructed using these independent predictive factors. The Hosmer-Lemeshow test yielded a Chi-Square value of 9.43 (p = 0.331), indicating a good fit for the model, and the calibration curve closely approximated the ideal model. The c-index for internal validation was 0.700 (0.560â0.834), further confirming the predictive performance of the model. Clinical decision analysis demonstrated that the nomogram model had good clinical utility, with an area under the ROC curve of 0.944 (95 % CI 0.903â0.963), indicating excellent discriminative ability. CONCLUSION: This study identified B-type natriuretic peptide, white blood cell count, systolic blood pressure, d-dimer, and the presence of respiratory failure as independent factors for in-hospital mortality in AMI patients undergoing emergency PCI. The nomogram model based on these factors showed high predictive accuracy and feasibility.
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Mortalidade Hospitalar , Infarto do Miocárdio , Nomogramas , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Fatores de Risco , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/sangue , Modelos LogísticosRESUMO
BACKGROUND: The impact of a healthy diet on the secondary prevention of ischemic stroke (IS) remains uncertain. Levels of low-density lipoprotein cholesterol (LDL-C) are inversely associated with the risk of IS recurrence. A Mediterranean diet (MeDi), consisting of a preference for fish/poultry, monosaturated fats from olive oil, fruit, vegetables, whole grains, legumes/nuts and limited red meats, animal fats and sweetened beverages, reduces metabolic syndrome, LDL-C levels and stroke risk. Avocados also reduce metabolic syndrome and LDL-C levels but are not part of the traditional MeDi diet. The effects of an avocado-based Mediterranean diet on LDL-C were investigated and compared to those of a low-fat diet in patients with previous IS. METHODS: The Avocado-Based Mediterranean Diet on Serum Lipids for Secondary Prevention after Ischemic Stroke (ADD-SPISE) was a prospective, randomized, open-label, blinded outcome assessment, phase 2, clinical trial. The participants were adults with an IS in the previous month who were randomly assigned at a 1:1 ratio to a MeDi or a low-fat diet for three months. Outcome assessors of laboratory results and data analysts were masked. The primary outcome was the mean difference in LDL-C between groups at 90 days, adjusted by statin use. Safety, feasibility and acceptability (assessed through a 14-item questionnaire administered to all patients who completed the follow-up) were also evaluated. RESULTS: From August 2018 to October 2022, 200 participants were enrolled (97 randomized to the low-fat diet and 103 to the MeDi), with 189 (94.5%) completing the study. There were no significant differences in LDL-C levels between the MeDi group and the low-fat group at 90 days: 66.5 mg/dL (95% confidence interval [CI] 59.6, 73.4) in the MeDi group and 69.9 mg/dL (62.6, 77.2) in the low-fat group at the end of follow-up. The adjusted difference was - 3.4 mg/dL (-13.4, -6.62); P = 0.50. The intervention group showed significant improvements in Mediterranean diet adherence (P < 0.01). Moreover, no significant differences in adverse events were observed between the groups. CONCLUSION: Compared with a low-fat diet, the avocado-based MeDi did not significantly lower LDL-C in IS patients after three months. The intervention was safe, feasible, and well accepted. Larger trials should establish whether longer dietary interventions could yield clinically significant benefits in these patients. The study is registered under ADD-SPISE at www. CLINICALTRIALS: gov . Identifier: NCT03524742.