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Authors = Nuno Sepulveda

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20 pages, 3369 KiB  
Article
IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry
by André Fonseca, Mateusz Szysz, Hoang Thien Ly, Clara Cordeiro and Nuno Sepúlveda
Medicina 2024, 60(1), 161; https://doi.org/10.3390/medicina60010161 - 15 Jan 2024
Cited by 1 | Viewed by 3974
Abstract
Background and Objectives: The diagnosis and pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. Materials and Methods: [...] Read more.
Background and Objectives: The diagnosis and pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. Materials and Methods: In this work, we analyzed a large public dataset on the IgG antibodies to 3054 EBV peptides to understand whether these immune responses could help diagnose patients and trigger pathological autoimmunity; we used healthy controls (HCs) as a comparator cohort. Subsequently, we aimed at predicting the disease status of the study participants using a super learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. Results: When we compared the data of all ME/CFS patients or the data of a subgroup of those patients with non-infectious or unknown disease triggers to the data of the HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. However, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from the HCs with 100% and 90% accuracies in the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. Conclusions: In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis in a subset of patients. However, the peptides associated with these antibodies are less likely to induce autoimmune B-cell responses that could explain the pathogenesis of ME/CFS. Full article
(This article belongs to the Section Hematology and Immunology)
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25 pages, 2278 KiB  
Article
Classification Methods for the Serological Status Based on Mixtures of Skew-Normal and Skew-t Distributions
by Tiago Dias-Domingues, Helena Mouriño and Nuno Sepúlveda
Mathematics 2024, 12(2), 217; https://doi.org/10.3390/math12020217 - 9 Jan 2024
Cited by 2 | Viewed by 1732
Abstract
Gaussian mixture models are widely employed in serological data analysis to discern between seropositive and seronegative individuals. However, serological populations often exhibit significant skewness, making symmetric distributions like Normal or Student-t distributions unreliable. In this study, we propose finite mixture models based on [...] Read more.
Gaussian mixture models are widely employed in serological data analysis to discern between seropositive and seronegative individuals. However, serological populations often exhibit significant skewness, making symmetric distributions like Normal or Student-t distributions unreliable. In this study, we propose finite mixture models based on Skew-Normal and Skew-t distributions for serological data analysis. Although these distributions are well established in the literature, their application to serological data needs further exploration, with emphasis on the determination of the threshold that distinguishes seronegative from seropositive populations. Our previous work proposed three methods to estimate the cutoff point when the true serological status is unknown. This paper aims to compare the three cutoff techniques in terms of their reliability to estimate the true threshold value. To attain this goal, we conducted a Monte Carlo simulation study. The proposed cutoff points were also applied to an antibody dataset against four SARS-CoV-2 virus antigens where the true serological status is known. For this real dataset, we also compared the performance of our estimated cutoff points with the ROC curve method, commonly used in situations where the true serological status is known. Full article
(This article belongs to the Special Issue Advances in Biostatistics and Applications)
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13 pages, 620 KiB  
Article
Feasibility and Outcomes of Meta Salud Diabetes Behavioral Health Intervention: A Pilot Study of a Community Health Worker-Administered Educational Intervention to Prevent Cardiovascular Disease and Its Complications among Hispanic Patients with Type-2 Diabetes
by Tomas Nuño, Maria Rocio Torres, Sheila Soto, Refugio Sepulveda, Benjamin Aceves and Cecilia Ballesteros Rosales
Int. J. Environ. Res. Public Health 2023, 20(21), 6968; https://doi.org/10.3390/ijerph20216968 - 24 Oct 2023
Viewed by 2285
Abstract
Background: Hispanics in the United States experience a greater burden of type-2 diabetes (T2D), with a prevalence rate (17%) more than twice that of non-Hispanic whites (8%). Cardiovascular disease (CVD) is the leading cause of death among people with T2D. A culturally appropriate [...] Read more.
Background: Hispanics in the United States experience a greater burden of type-2 diabetes (T2D), with a prevalence rate (17%) more than twice that of non-Hispanic whites (8%). Cardiovascular disease (CVD) is the leading cause of death among people with T2D. A culturally appropriate behavioral health intervention that addresses healthy lifestyle promotion is an impactful approach for health systems with scarce medical resources and a high prevalence of chronic conditions, including obesity and high blood pressure, which increase the likelihood of CVD mortality among type-2 diabetics. Purpose: To assess the feasibility and outcomes of a behavioral intervention to decrease CVD and complications in a Hispanic diabetic population. Methods: Meta Salud Diabetes (MSD), a behavioral intervention effective in a Mexican population, consists of a 13-week intervention addressing CVD and T2D knowledge and risk reduction. It was implemented in a sample of Hispanic diabetic patients from two federally qualified health centers (FQHCs). Clinical and behavioral variables were measured at baseline, postintervention, and 1-year follow-up. Results: The feasibility of MSD was rated as successful by all FQHC staff and well-received by both staff and study participants, with positive remarks about the culturally relevant components of the intervention. The sample size was n = 30 (baseline), n = 23 (postintervention), and n = 19 (1-year follow-up). Of note, quantitative results showed trending decreases in Hba1c (7.06; 6.80; 6.30), blood pressure (132/83; 126/80; 123/78), and total cholesterol (160; 159; 154). Conclusion: MSD is a feasible intervention and can address the need to improve health outcomes among Hispanic patients with T2D. Full article
(This article belongs to the Special Issue Health and Healthcare for People with Diabetes)
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25 pages, 3383 KiB  
Article
Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation
by Anna D. Grabowska, Mateusz Wątroba, Joanna Witkowska, Agnieszka Mikulska, Nuno Sepúlveda and Dariusz Szukiewicz
Int. J. Mol. Sci. 2023, 24(14), 11640; https://doi.org/10.3390/ijms241411640 - 19 Jul 2023
Cited by 10 | Viewed by 2201
Abstract
The flow of substances between the blood and the central nervous system is precisely regulated by the blood–brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to [...] Read more.
The flow of substances between the blood and the central nervous system is precisely regulated by the blood–brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, and increase the risk of developing neurodegenerative diseases. One of the most studied natural anti-diabetic, anti-inflammatory, and neuroprotective compounds is resveratrol (RSV). It activates sirtuin 1 (SIRT1), a key metabolism regulator dependent on cell energy status. The aim of this study was to assess the astrocyte SIRT1 response to neuroinflammation and subsequent RSV treatment, depending on systemic glycemia. For this purpose, we used an optimized in vitro model of the BBB consisting of endothelial cells and astrocytes, representing microvascular and brain compartments (MC and BC), in different glycemic backgrounds. Astrocyte-secreted SIRT1 reached the highest concentration in hypo-, the lowest in normo-, and the lowest in hyperglycemic backgrounds. Lipopolysaccharide (LPS)-induced neuroinflammation caused a substantial decrease in SIRT1 in all glycemic backgrounds, as observed earliest in hyperglycemia. RSV partially counterbalanced the effect of LPS on SIRT1 secretion, most remarkably in normoglycemia. Our results suggest that abnormal glycemic states have a worse prognosis for RSV-therapy effectiveness compared to normoglycemia. Full article
(This article belongs to the Special Issue Astrocyte-Endothelial Interactions at the Blood-Brain Barrier)
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11 pages, 352 KiB  
Article
Risk Factors Associated with Diabetes among Mexican-Origin Adults in Southern Arizona
by Mario Morales, Maia Ingram, Ramses Sepulveda, Thomas Nuño, Ada M. Wilkinson-Lee, Jill E. Guernsey De Zapien and Scott Carvajal
Int. J. Environ. Res. Public Health 2023, 20(12), 6126; https://doi.org/10.3390/ijerph20126126 - 14 Jun 2023
Viewed by 1990
Abstract
Diabetes is the seventh leading cause of death in the United States, and it is particularly problematic among the Latine population. This study employed multivariable logistic regression models to examine how hypertension, depression, and sociodemographics were associated with diabetes in a cross-sectional sample [...] Read more.
Diabetes is the seventh leading cause of death in the United States, and it is particularly problematic among the Latine population. This study employed multivariable logistic regression models to examine how hypertension, depression, and sociodemographics were associated with diabetes in a cross-sectional sample of Mexican-origin adults living in three counties of Southern Arizona. The overall prevalence of diabetes from this primary care sample was 39.4%. Holding covariates at fixed values, individuals having hypertension were 2.36 (95% CI: 1.15, 4.83) times more likely to have diabetes, when compared to individuals not having hypertension. The odds of having diabetes for individuals with ≥12 years of educational attainment were 0.29 (95% CI: 0.14, 0.61) times the corresponding odds of individuals with <12 years of educational attainment. For individuals with depression, the odds of having diabetes for those who were born in Mexico and had <30 years living in the US were 0.04 (95% CI: 0, 0.42) times the corresponding odds of individuals without depression and who were born in the US. Findings suggest clinical and public health systems should be aware of the potential increased risk of diabetes among Mexican-origin adults with hypertension and lower educational attainment. Full article
(This article belongs to the Special Issue Diabetes and Related Disorder Care Management Research)
18 pages, 869 KiB  
Article
Epidemiologic Factors Supporting Triage of Infected Dog Patients Admitted to a Veterinary Hospital Biological Isolation and Containment Unit
by Inês Cunha Machado, Telmo Nunes, Miguel Maximino, João Malato, Luís Tavares, Virgilio Almeida, Nuno Sepúlveda and Solange Gil
Vet. Sci. 2023, 10(3), 186; https://doi.org/10.3390/vetsci10030186 - 1 Mar 2023
Cited by 4 | Viewed by 3820
Abstract
The teaching hospital of the Faculty of Veterinary Medicine at the University of Lisbon hosts a Biological Isolation and Containment Unit (BICU) for the hospitalization of both confirmed and suspected animals of an infectious disease. This study targets the BICU dog population to [...] Read more.
The teaching hospital of the Faculty of Veterinary Medicine at the University of Lisbon hosts a Biological Isolation and Containment Unit (BICU) for the hospitalization of both confirmed and suspected animals of an infectious disease. This study targets the BICU dog population to identify and characterize the most frequent infectious diseases recorded in a 7-year period. Several epidemiologic factors were analyzed for their significance to triage infected cases. During the study period, 534 dogs were admitted, of which 263 (49.3%) had a confirmed infectious disease diagnosis: parvovirosis (49.4%; n = 130); leptospirosis (21.7%; n = 57); multidrug-resistant (MDR) bacterial infection; (10.6%; n = 28), and canine distemper (9.9%; n = 26). Several potential risk factors for these diseases were identified: age under 2 years old (p < 0.001), incomplete vaccination for parvovirosis (p < 0.001), age ≥ 10 years old (p < 0.001), and the presence of concomitant disorders for MDR-infected cases (p = 0.03). Logistic regression models were constructed to classify cases and controls. The sensitivity and specificity estimates were very high (>0.83) for parvovirosis, MDR, and distemper infections. A lower sensitivity (0.77) was obtained for identifying cases with leptospirosis. In conclusion, infectious diseases are frequent, hence, it is essential to decrease their occurrence through effective preventive measures such as vaccination. The constructed logistic models can also help in triaging admitted dogs with a potential infectious disease. Full article
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16 pages, 516 KiB  
Article
Impact of Misdiagnosis in Case-Control Studies of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
by João Malato, Luís Graça and Nuno Sepúlveda
Diagnostics 2023, 13(3), 531; https://doi.org/10.3390/diagnostics13030531 - 1 Feb 2023
Cited by 5 | Viewed by 4146
Abstract
Misdiagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can occur when different case definitions are used by clinicians (relative misdiagnosis) or when failing the genuine diagnosis of another disease (misdiagnosis in a strict sense). This problem translates to a recurrent difficulty in reproducing research [...] Read more.
Misdiagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can occur when different case definitions are used by clinicians (relative misdiagnosis) or when failing the genuine diagnosis of another disease (misdiagnosis in a strict sense). This problem translates to a recurrent difficulty in reproducing research findings. To tackle this problem, we simulated data from case-control studies under misdiagnosis in a strict sense. We then estimated the power to detect a genuine association between a potential causal factor and ME/CFS. A minimum power of 80% was obtained for studies with more than 500 individuals per study group. When the simulation study was extended to the situation where the potential causal factor could not be determined perfectly (e.g., seropositive/seronegative in serological association studies), the minimum power of 80% could only be achieved in studies with more than 1000 individuals per group. In conclusion, current ME/CFS studies have suboptimal power under the assumption of misdiagnosis. This power can be improved by increasing the overall sample size using multi-centric studies, reporting the excluded illnesses and their exclusion criteria, or focusing on a homogeneous cohort of ME/CFS patients with a specific pathological mechanism where the chance of misdiagnosis is reduced. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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25 pages, 1253 KiB  
Opinion
European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe
by Luis Nacul, François Jérôme Authier, Carmen Scheibenbogen, Lorenzo Lorusso, Ingrid Bergliot Helland, Jose Alegre Martin, Carmen Adella Sirbu, Anne Marit Mengshoel, Olli Polo, Uta Behrends, Henrik Nielsen, Patricia Grabowski, Slobodan Sekulic, Nuno Sepulveda, Fernando Estévez-López, Pawel Zalewski, Derek F. H. Pheby, Jesus Castro-Marrero, Giorgos K. Sakkas, Enrica Capelli, Ivan Brundsdlund, John Cullinan, Angelika Krumina, Jonas Bergquist, Modra Murovska, Ruud C. W. Vermuelen and Eliana M. Lacerdaadd Show full author list remove Hide full author list
Medicina 2021, 57(5), 510; https://doi.org/10.3390/medicina57050510 - 19 May 2021
Cited by 115 | Viewed by 29405
Abstract
Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)—COST action 15111—from 2016 to 2020. The main goal of the Cost Action [...] Read more.
Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)—COST action 15111—from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS. Full article
(This article belongs to the Special Issue ME/CFS: Causes, Clinical Features and Diagnosis)
15 pages, 708 KiB  
Review
Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology
by Fernando Estévez-López, Kathleen Mudie, Xia Wang-Steverding, Inger Johanne Bakken, Andrejs Ivanovs, Jesús Castro-Marrero, Luis Nacul, Jose Alegre, Paweł Zalewski, Joanna Słomko, Elin Bolle Strand, Derek Pheby, Evelina Shikova, Lorenzo Lorusso, Enrica Capelli, Slobodan Sekulic, Carmen Scheibenbogen, Nuno Sepúlveda, Modra Murovska and Eliana Lacerda
J. Clin. Med. 2020, 9(5), 1557; https://doi.org/10.3390/jcm9051557 - 21 May 2020
Cited by 51 | Viewed by 10754
Abstract
This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a [...] Read more.
This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a backward-(reference lists) and forward-(citations) search of the works included in this review. Grey literature was addressed by contacting all members of the European Network on ME/CFS (EUROMENE). Independent reviewers searched, screened and selected studies, extracted data and evaluated the methodological and reporting quality. For prevalence, two studies in adults and one study in adolescents were included. Prevalence ranged from 0.1% to 2.2%. Two studies also included incidence estimates. In conclusion, studies on the prevalence and incidence of ME/CFS in Europe were scarce. Our findings point to the pressing need for well-designed and statistically powered epidemiological studies. To overcome the shortcomings of the current state-of-the-art, EUROMENE recommends that future research is better conducted in the community, reviewing the clinical history of potential cases, obtaining additional objective information (when needed) and using adequate ME/CFS case definitions; namely, the Centers for Disease Control & Prevention−1994, Canadian Consensus Criteria, or Institute of Medicine criteria. Full article
(This article belongs to the Section Epidemiology & Public Health)
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