Around 1% of the population worldwide suffer from epilepsy, a condition which is characterized by recurring seizures. The development of reliable biomarkers for both prediction and targeted treatment of seizures is critical, as they can pave the way towards personalized therapy in epilepsy. In addition, sensitive biomarkers can be utilized for the detection of epilepsy in its early stages and allow for early treatment intervention. Various types of biomarkers have been studied in relation to epilepsy, with blood markers emerging as major candidates. Blood biomarkers offer the benefit of being cost and time efficient, in addition to being less invasive to sample in contrast to cerebrospinal fluid markers. Importantly, they can enhance patient diagnosis and prognosis when supplemented with other diagnostic methods, such as EEG. In this pilot study, five blood biomarkers of brain injury are studied in epilepsy, post-stroke epilepsy and single seizure patients. The aim is to analyze whether S100B, NSE, GFAP, NfL and tau are promising indicators of epilepsy after a first seizure in adults. The results present S100B as the most promising biomarker, with potential to predict early epilepsy.

Role of blood biomarkers in spontaneous intracerebral hemorrhage Background: The study of blood biomarkers can offer new possibilities in diagnostics, prognostication, determination of etiology, and management of spontaneous intracerebral hemorrhage. The aim of our study was to assess the relationship between a panel of selected blood biomarkers and clinical and radiodiagnostic parameters in patients with spontaneous intracerebral hemorrhage. Primarily, the aim was to find a prognostic biomarker which could help in deciding on the optimal categorization of treatment. Patients and methods: A total of 70 patients were prospectively included in this study. The following blood biomarkers were determined: glial fibrillary acidic protein, S100B protein, matrix metalloproteinase 9, interleukin 6, interleukin 10, 25-hydroxyvitamin D, 1,25- dihydroxyvitamin D, total cholesterol, leukocyte counts, blood glucose and C-reactive protein. These were then correlated with selected clinical and radiodiagnostic parameters. Results: Relative to hematoma volume a statistically significant positive correlation was found for S100B, interleukin 10, interleukin 6 and blood glucose (S100B: ρ= 0,54, p< 0,001, IL-10: ρ= 0,43, p< 0,001, IL-6: ρ= 0,26, p= 0,027, blood glucose: ρ= 0,24, p= 0,045). Using multivariate analysis, a...

One of the pressing needs in the field of disease biomarker discovery is new technologies that could allow high performance protein analysis in different types of clinical material, such as blood and solid tissues. This thesis includes four approaches that address important limitations of current technologies, thus enabling highly sensitive, specific and parallel protein measurements. Paper I describes a method for sensitive singleplex protein detection in complex biological samples, namely solid phase proximity ligation assay (SP-PLA). SP-PLA exhibited improved sensitivity compared to conventional sandwich immunoassays. We applied SP-PLA to validate the potential of GDF-15 as a biomarker for cardiovascular disease.   Paper II describes ProteinSeq, a multiplexed immunoassay based on the principle of SP-PLA, for parallel detection of 36 proteins using next-generation sequencing as readout. ProteinSeq exhibited improved sensitivity compared to multiplexed sandwich immunoassays, and the potential to achieve even higher levels of multiplexing while preserving a high sensitivity and specificity. We applied ProteinSeq to analyze 36 proteins, including one internal control, in 5 μl of plasma samples in a cohort of patients with cardiovascular disease and healthy controls. Paper III describes PLA-DTM, a strategy for recording all possible interactions between sets of proteins in clinical samples. Individual proteins and their interactions are first encoded to dual barcoded DNA by PLA, and the barcodes are interrogated by a method named dual tag microarray (DTM). We applied the method for studying interactions among protein members of the NFκB signaling pathway. Paper IV describes a novel probing strategy for analyzing individual biomolecules in solution or in situ. The technique employs a new class of probes for unfolding proximity ligation assays - uPLA probes. The probes are designed so that each probe set is sufficient in forming and replicating circular DNA reporter, without interactions among themselves when incubated with the sample. The uPLA probing strategy provides ease in the design of multiple probe sets in parallelized assays while enhancing the specificity of detection. We used the uPLA probes to detect various targets, including synthetic DNA and cancer-related transcripts in situ.

Une meilleure compréhension des mécanismes de résistance aux agents pathogènes couplée à une caractérisation de la capacité immune devient un axe de recherche prioritaire en élevage. L’objectif global de la thèse est d’exploiter des informations de phénotypage, de génétique et de génomique pour étudier l’architecture génétique de la capacité immune chez le porc et contribuer à l’identification de marqueurs génétiques et de biomarqueurs sanguins prédictifs de variations de niveaux de paramètres immuns. Le projet s’articule autour de trois axes complémentaires et les résultats obtenus sont basés sur l’exploitation des jeux de données issus des projets IMMOPIG et SUS_FLORA financés par l’ANR, pour lesquels des cohortes de 450 et 560 porcelets ont été prélevés à 60 jours d’âge, trois semaines après une vaccination contre Mycoplasma hyopneumoniae.Nous avons analysé le déterminisme génétique de l’expression des gènes dans le sang par une analyse eGWAS (génotypage 60K SNP et transcriptome du sang pour 242 animaux) validée pour partie par une étude de la régulation spécifique d’allèles (ASE) des transcrits (RNA-Seq sur 38 animaux). Les résultats d’eGWAS mettent en évidence de multiples associations locales (n=2839) et à distance (n=1752) entre des polymorphes SNP et des variations de transcription, réparties sur l’ensemble des chromosomes. Les analyses ASE confirment l’importance du contrôle génétique en cis, avec une régulation allélique trouvée pour 763 gènes. Les fonctions biologiques associées sont notamment reliées au processing des ARN et à l’immunité. La région du complexe majeur d’histocompatibilité a été trouvée particulièrement riche en eQTL et ASE. L’ensemble de ces données a permis d’établir, pour le porc, une première cartographie des eQTL et gènes soumis à ASE dans le sang.Nous avons étudié les co-variations entre des paramètres immunitaires et le transcriptome du sang pour 243 individus. Les paramètres immunitaires incluent la numération formule sanguine, la caractérisation de sous-populations cellulaires par cytomètre de flux, des dosages sériques (protéine C réactive, haptoglobine, anticorps spécifiques anti Mycoplasma hyopneumoniae), des dosages de réponse suite à des stimulations in vitro du sang total (phagocytose, cytokines IL1b, IL2, IL6, IL8, IL10, TNFa, INFg). Nous avons confirmé l’héritabilité de nombreux paramètres immuns et identifié des covariations avec des profils géniques, offrant des hypothèses sur des biomarqueurs candidats.Nous avons également conduit une analyse fonctionnelle sur quatre animaux de 70 jours d’âge pour caractériser et comparer les profils de transcrits du sang et de trois tissus lymphoïdes associés au tube digestif (ganglion mésentérique, plaques de Peyer jéjunales et iléales). Les données RNA-Seq ont mis en évidence des différentiels d’expression entre les tissus, ce nombre étant plus limité entre les deux types de plaques de Peyer. De manière tout à fait intéressante, parmi les fonctions biologiques enrichies par les gènes différentiellement exprimés entre les deux plaques de Peyer, sont identifiées les voies de différenciation lymphocytaires Th1 et Th2, en cohérence avec une surabondance de lymphocytes B dans les plaques de Peyer iléales.L’ensemble de ces résultats apporte des informations nouvelles pour avancer dans la compréhension du déterminisme génétique des variations de paramètres immunitaires chez le porc, la recherche de polymorphismes causaux de ces variations et l’identification de biomarqueurs sanguins pertinents pour phénotyper la compétence immunitaire. / A better understanding of the mechanisms for resistance to pathogens along with the characterization of the immune capacity has become a priority for research in breeding. The overall objective of this PhD project was to use phenotyping, genetic and genomic information to study the genetic architecture of the immune capacity in the pig and to contribute to the identification of genetic markers and blood biomarkers that predict variations of immune parameter levels. The study was focused on three complementary axes and the results obtained were based on the use of data collected as part of the IMMOPIG and SUS_FLORA projects financed by the ANR, for which 450 and 560 piglet cohorts were sampled at 60 days of age, three weeks after vaccination against Mycoplasma hyopneumoniae.We analyzed the genetic determinism of gene expression in the blood using an eGWAS (60K SNP genotyping and blood transcriptome for 242 animals) confirmed in part by an allele specific expression (ASE) of transcripts (RNA-Seq on 38 animals). The eGWAS results showed multiple local (n=2839) and distant associations between the SNP polymorphisms and transcription variations, spread over all the chromosomes. The ASE analyses confirmed the cis genetic control of gene expression, with allele regulation being found for 763 genes. The biological functions associated were notably associated with RNA processing and immunity. The region of the major histocompatibility complex was found particularly rich in eQTL signals and genes with ASE in the blood.We studied the co-variations between immune parameters and blood transcriptomes for 243 individuals. The immune parameters included the blood count, cell subpopulation characterization by flow cytometry, serum assays (reactive C protein, haptoglobin, antibodies specific for Mycoplasma hyopneumoniae), immune response after in vitro stimulation of peripheral blood (phagocytosis, IL1b, IL2, IL6, IL8, IL10, TNFa, INFg cytokines). We confirmed the heritability of numerous immune parameters and identified covariations with gene profiles, providing hypotheses on biomarker candidates.We also led a functional analysis on four animals at 70 days-of-age in order to characterize and compare the transcriptome profiles of peripheral blood and three gut-associated lymphoid tissues (mesenteric lymph nodes, jejunal and ileal Payer’s patches). The RNA-Seq data showed differential expression between tissues; this number was more limited between the two types of Peyer’s patches. Interestingly, among the biological functions enriched by the differentially expressed genes between the Peyer’s patches, we identified the Th1 and Th2 lymphocyte differentiation pathways, which was in agreement with an over-abundance of B lymphocytes in the ileal Peyer’s patches.Together these results provide new information on the understanding of the genetic determinism of immune parameter variations in the pig, the search for causal polymorphisms of these variations and the identification of relevant blood biomarkers for phenotyping immune competence.

Fundamentação: O acidente vascular cerebral (AVC) é uma das principais causas de morte em todo o mundo e a maioria dos sobreviventes permanece com alguma sequela neurológica após o evento agudo. O presente estudo objetiva investigar a associação de alguns biomarcadores sanguíneos com as escalas de AVC, bem como avaliar a capacidade dos biomarcadores selecionados na predição de desfechos neurológicos durante o tempo de acompanhamento. Material e Métodos: Incluímos nesse estudo 60 pacientes com AVC agudo admitidos na unidade neurovascular da emergência ou na unidade de medicina intensiva do Hospital de Clínicas de Porto Alegre, nas primeiras 24 horas do início dos sintomas. Foram coletas amostras sanguíneas nas primeiras 24 horas, no terceiro e no quinto dias após o AVC para dosagem de enolase neurônio específica (ENS), proteína S100ß (S100ß), interleucina 6 (IL-6), proteína C reativa (PCR) e fator neurotrófico derivado do cérebro (BDNF). A gravidade do AVC e o grau de dependência funcional dos pacientes após o AVC foram mensurados através das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS) nos três momentos das coletas sanguíneas e na alta hospitalar. Resultados: Os níveis séricos de S100ß, IL-6 e PCR mostraram-se o melhor painel de biomarcadores após o AVC nesse estudo. Quando os pacientes foram subdivididos em dois grupos para a avaliação de desfechos neurológicos, usando as escalas do NIHSS (NIHSS ≤ 6 e NHISS > 6) e mRS (mRS ≤ 3 e mRS > 3), ambas as escalas apresentaram boa associação entre as concentrações de S100ß e de IL-6 em todas as medidas e as escalas de AVC para bom prognóstico (NIHSS ≤ 6 e mRS ≤ 3) na alta hospitalar. Dentre os biomarcadores selecionados para o estudo, foram os três citados acima que apresentaram as melhores correlações com as escalas de AVC e com o prognóstico pós AVC durante o tempo de acompanhamento. Conclusão: Os biomarcadores séricos podem ser úteis na avaliação da gravidade e do prognóstico após o AVC. A associação de S100ß, IL-6 e PCR parece acrescentar pouco às escalas validadas de AVC na capacidade de predizer desfechos após o evento agudo. / Background and Purpose: Stroke is an important cause of death worldwide, and the majority of stroke survivors suffer from some form of residual disability. This study aimed to investigate the association of blood biomarkers with stroke scales and their predictive value after acute stroke at the time of admission until hospital discharge. Design and Methods: We investigated 60 patients with acute stroke who were admitted within 24 h of event onset at the intensive care unit or neurovascular emergency unit of Clínicas Hospital. All patients provided venous blood samples for the measurement of neuron-specific enolase (NSE), S100ß protein (S100ß), interleukin-6 (IL-6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) within 24 h of the acute event, on the third day and on the fifth day after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times of blood collection and at the time of hospital discharge. Results: The serum levels of the S100ß protein, IL-6 and CRP seem to constitute the best panel of biomarkers after acute stroke in this study. When patients were subdivided into two groups according to the NIHSS (NIHSS ≤ 6 and NIHSS > 6) and mRS (mRS ≤ 3 and mRS > 3) scores, which were used as neurological outcome measures, both neurologic scores for good outcome (NIHSS ≤ 6 and mRS ≤ 3) at hospital discharge were significantly related to the S100ß protein and IL-6 levels at all of the measured time points. Among the analyzed blood markers, S100ß, IL-6 and PCR levels significanttly correlated with the stroke scales and prognostic value. Conclusion: Blood biomarkers may be useful in acute stroke either by suggesting stroke severity or providing a prognostic value. The addition of the S100ß protein, IL-6 and CRP to previously validated stroke scales slightly improves the ability of these scales to predict outcome.

Fundamentação: O acidente vascular cerebral (AVC) é uma das principais causas de morte em todo o mundo e a maioria dos sobreviventes permanece com alguma sequela neurológica após o evento agudo. O presente estudo objetiva investigar a associação de alguns biomarcadores sanguíneos com as escalas de AVC, bem como avaliar a capacidade dos biomarcadores selecionados na predição de desfechos neurológicos durante o tempo de acompanhamento. Material e Métodos: Incluímos nesse estudo 60 pacientes com AVC agudo admitidos na unidade neurovascular da emergência ou na unidade de medicina intensiva do Hospital de Clínicas de Porto Alegre, nas primeiras 24 horas do início dos sintomas. Foram coletas amostras sanguíneas nas primeiras 24 horas, no terceiro e no quinto dias após o AVC para dosagem de enolase neurônio específica (ENS), proteína S100ß (S100ß), interleucina 6 (IL-6), proteína C reativa (PCR) e fator neurotrófico derivado do cérebro (BDNF). A gravidade do AVC e o grau de dependência funcional dos pacientes após o AVC foram mensurados através das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS) nos três momentos das coletas sanguíneas e na alta hospitalar. Resultados: Os níveis séricos de S100ß, IL-6 e PCR mostraram-se o melhor painel de biomarcadores após o AVC nesse estudo. Quando os pacientes foram subdivididos em dois grupos para a avaliação de desfechos neurológicos, usando as escalas do NIHSS (NIHSS ≤ 6 e NHISS > 6) e mRS (mRS ≤ 3 e mRS > 3), ambas as escalas apresentaram boa associação entre as concentrações de S100ß e de IL-6 em todas as medidas e as escalas de AVC para bom prognóstico (NIHSS ≤ 6 e mRS ≤ 3) na alta hospitalar. Dentre os biomarcadores selecionados para o estudo, foram os três citados acima que apresentaram as melhores correlações com as escalas de AVC e com o prognóstico pós AVC durante o tempo de acompanhamento. Conclusão: Os biomarcadores séricos podem ser úteis na avaliação da gravidade e do prognóstico após o AVC. A associação de S100ß, IL-6 e PCR parece acrescentar pouco às escalas validadas de AVC na capacidade de predizer desfechos após o evento agudo. / Background and Purpose: Stroke is an important cause of death worldwide, and the majority of stroke survivors suffer from some form of residual disability. This study aimed to investigate the association of blood biomarkers with stroke scales and their predictive value after acute stroke at the time of admission until hospital discharge. Design and Methods: We investigated 60 patients with acute stroke who were admitted within 24 h of event onset at the intensive care unit or neurovascular emergency unit of Clínicas Hospital. All patients provided venous blood samples for the measurement of neuron-specific enolase (NSE), S100ß protein (S100ß), interleukin-6 (IL-6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) within 24 h of the acute event, on the third day and on the fifth day after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times of blood collection and at the time of hospital discharge. Results: The serum levels of the S100ß protein, IL-6 and CRP seem to constitute the best panel of biomarkers after acute stroke in this study. When patients were subdivided into two groups according to the NIHSS (NIHSS ≤ 6 and NIHSS > 6) and mRS (mRS ≤ 3 and mRS > 3) scores, which were used as neurological outcome measures, both neurologic scores for good outcome (NIHSS ≤ 6 and mRS ≤ 3) at hospital discharge were significantly related to the S100ß protein and IL-6 levels at all of the measured time points. Among the analyzed blood markers, S100ß, IL-6 and PCR levels significanttly correlated with the stroke scales and prognostic value. Conclusion: Blood biomarkers may be useful in acute stroke either by suggesting stroke severity or providing a prognostic value. The addition of the S100ß protein, IL-6 and CRP to previously validated stroke scales slightly improves the ability of these scales to predict outcome.

Fundamentação: O acidente vascular cerebral (AVC) é uma das principais causas de morte em todo o mundo e a maioria dos sobreviventes permanece com alguma sequela neurológica após o evento agudo. O presente estudo objetiva investigar a associação de alguns biomarcadores sanguíneos com as escalas de AVC, bem como avaliar a capacidade dos biomarcadores selecionados na predição de desfechos neurológicos durante o tempo de acompanhamento. Material e Métodos: Incluímos nesse estudo 60 pacientes com AVC agudo admitidos na unidade neurovascular da emergência ou na unidade de medicina intensiva do Hospital de Clínicas de Porto Alegre, nas primeiras 24 horas do início dos sintomas. Foram coletas amostras sanguíneas nas primeiras 24 horas, no terceiro e no quinto dias após o AVC para dosagem de enolase neurônio específica (ENS), proteína S100ß (S100ß), interleucina 6 (IL-6), proteína C reativa (PCR) e fator neurotrófico derivado do cérebro (BDNF). A gravidade do AVC e o grau de dependência funcional dos pacientes após o AVC foram mensurados através das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS) nos três momentos das coletas sanguíneas e na alta hospitalar. Resultados: Os níveis séricos de S100ß, IL-6 e PCR mostraram-se o melhor painel de biomarcadores após o AVC nesse estudo. Quando os pacientes foram subdivididos em dois grupos para a avaliação de desfechos neurológicos, usando as escalas do NIHSS (NIHSS ≤ 6 e NHISS > 6) e mRS (mRS ≤ 3 e mRS > 3), ambas as escalas apresentaram boa associação entre as concentrações de S100ß e de IL-6 em todas as medidas e as escalas de AVC para bom prognóstico (NIHSS ≤ 6 e mRS ≤ 3) na alta hospitalar. Dentre os biomarcadores selecionados para o estudo, foram os três citados acima que apresentaram as melhores correlações com as escalas de AVC e com o prognóstico pós AVC durante o tempo de acompanhamento. Conclusão: Os biomarcadores séricos podem ser úteis na avaliação da gravidade e do prognóstico após o AVC. A associação de S100ß, IL-6 e PCR parece acrescentar pouco às escalas validadas de AVC na capacidade de predizer desfechos após o evento agudo. / Background and Purpose: Stroke is an important cause of death worldwide, and the majority of stroke survivors suffer from some form of residual disability. This study aimed to investigate the association of blood biomarkers with stroke scales and their predictive value after acute stroke at the time of admission until hospital discharge. Design and Methods: We investigated 60 patients with acute stroke who were admitted within 24 h of event onset at the intensive care unit or neurovascular emergency unit of Clínicas Hospital. All patients provided venous blood samples for the measurement of neuron-specific enolase (NSE), S100ß protein (S100ß), interleukin-6 (IL-6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) within 24 h of the acute event, on the third day and on the fifth day after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times of blood collection and at the time of hospital discharge. Results: The serum levels of the S100ß protein, IL-6 and CRP seem to constitute the best panel of biomarkers after acute stroke in this study. When patients were subdivided into two groups according to the NIHSS (NIHSS ≤ 6 and NIHSS > 6) and mRS (mRS ≤ 3 and mRS > 3) scores, which were used as neurological outcome measures, both neurologic scores for good outcome (NIHSS ≤ 6 and mRS ≤ 3) at hospital discharge were significantly related to the S100ß protein and IL-6 levels at all of the measured time points. Among the analyzed blood markers, S100ß, IL-6 and PCR levels significanttly correlated with the stroke scales and prognostic value. Conclusion: Blood biomarkers may be useful in acute stroke either by suggesting stroke severity or providing a prognostic value. The addition of the S100ß protein, IL-6 and CRP to previously validated stroke scales slightly improves the ability of these scales to predict outcome.

Background: To reduce the reliance on clinical judgment for the regulation of sports-related traumatic brain injury, identifying and measuring objective to biofluid biomarkers can provide important insight into the diagnosis (Determining the type and origin of a disorder) and prognosis (Determining the chance of survival of a disorder) of SR-TBIs. A biomarker is a qualitative or quantitative measurement that provides a measure of a subject’s physiological or pathological condition at a specific time or during a disease state. Recent literature has suggested that biomarkers can help in the screening of patients exhibiting symptoms of mild traumatic brain injury (mTBI). Despite insights from recent research, it is not clear whether biomarkers and assessments of sports-related TBI are well-aligned. The objective of this study sought to review the current literature on predictive values of biomarkers: glial fibrillary acidic protein (GFAP), calcium channel binding protein S100 subunit beta (S100β), total-tau and neuron-specific enolase (NSE) for sports-related Traumatic Brain Injuries (SR-TBIs) to improve comprehension of biological and clinical contexts that can help evaluate the use of these biomarkers in sports-related TBIs and their potential function. Methods: The study was reported based on guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA: 2020 Edition) of 8 studies related to the assessment of biomarkers concerning SR-TBI. Literature searches were carried out on PubMed, Google Scholar, ScienceDirect, and ResearchGate. With an evidentiary table, the characteristics of the studies included in the meta-analysis (n = 14 studies) were presented. A significant role for biomarkers in the management of mild traumatic brain injury is suggested by the results of this analysis. From the literature, the significance of biomarkers in SR-TBI was identified along with the biomarkers that can facilitate more accurate clinical decision-making. Results:The initial search resulted in 73 articles, and the application of exclusion criteria and removal of duplicates resulted in the inclusion of 14 articles. Eight of the included studies were ([26], [27], [28], [30], [34], [39], [40], [41]), three were cohort studies ([25], [37], [45]) one was a pilot study [32], one interview, and an observational study [44]. The review was carried out to determine the efficacy of Biomarkers GFAP, S100β, Total-tau, and NSE to help in the screening of mild traumatic brain injury (mTBI) in patients showing symptoms. The focus is on athletes presenting at an emergency department with possible mTBI requiring a CT scan based on the application of a clinical algorithm. A forest plot was utilized, and the studies had low heterogeneity or variability (P Conclusions: It was established that the utility of biofluid biomarkers in the prediction of mild traumatic brain injury due to SRC is significant when the markers are used in large combinations. The four biofluid biomarkers (S100β, total-tau, GFAP, NSE) under study have strong predictive ability for mTBI, and their use can reduce the number of CT scans among TBI patients participating in athletic activities. Although preliminary evidence shows that other diagnostic treatments may help to mitigate traumatic brain injury sequelae, clinical trials are needed to further test their efficacy, specifically with diverse and high-risk populations. Luckily, the research on mTBI biomarkers is rapidly advancing, and should these biomarkers be better established clinically, they could easily hold many important roles.

La dieta, lo stato nutrizionale e la salute sono questioni strettamente correlate sia nei paesi industrializzati che in quelli in via di sviluppo. In questa tesi di dottorato, l'obiettivo principale è stato quello di valutare lo stato nutrizionale come passo prodromico per migliorarlo per ottimizzare la salute. Nei paesi industrializzati è stato condotto un caso studio sullo stato nutrizionale di una popolazione dell'Italia centrale; l’ingestione di alcuni gruppi di alimenti, di origine animale e vegetale, è stata valutata mediante questionari di frequenza alimentare e alcuni biomarcatori del sangue. I risultati hanno dimostrato che nei controlli della dieta, al fine di accertarne gli effetti a lungo termine sulla salute, le misurazioni dei consumi tramite questionari non possono essere esclusive, ma alcuni indici ematici ed antropometrici potrebbero essere utili. Nei paesi in via di sviluppo, due casi di studio in zone rurali dell’India e della Repubblica Democratica del Congo hanno confermato che la malnutrizione è un problema serio; in particolare nei bambini di 3-5 anni con il 26% di malnutrizione cronica severa in India e oltre il 60% in R D Congo. Possibili percorsi per migliorare le condizioni di vita delle comunità rurali povere includono la produzione di cibi appropriati per una dieta migliore, nuove attività generatrici di reddito, miglioramento della nutrizione infantile, riduzione delle malattie causate dalla contaminazione di alimentari e dell’acqua, metodi di conservazione degli alimenti a livello domestico, etc.; i risultati di diverse prove sono stati discussi. / The diet, nutritional status and health are tightly related issues both in industrialized and developing countries. In this doctoral thesis, the main objective was the assessment of nutritional status as a prodromic step to improve it and consenquently health. In industrialized countries, a case study was the nutritional status of a population of central Italy; the intake of some groups of foods, of animal and plant origin, was estimated by food frequency questionnaires and some blood biomarkers. The results demostrated that in dietary controls, aiming to ascertain the long-term effects on health, consumption measurements by questionnaires cannot be exclusive, but some blood and anthropometric indexes could be also useful. In developing countries, two case studies in rural India and D R Congo confirmed that malnutrition is a serious issue; particularly in 3-5 years old children with 26% of severe chronic malnutrition in India and more than 60% in D R Congo. Possible pathways to improve livelihood of rural poor comunities including appropriate food production for a better diet, new income generating activities, infant nutrition improvement, food and waterborn diseases reduction, household food preservation, etc., have been analyzed and the risults of different related trials have been discussed.