Diploma thesis "Diagnosis of developmental dyspraxia in children and adolescents with a focus on the preference of the upper or lower extremities in sport" summarizes all available information about etiology, diagnosis and therapy of developmental dyspraxia in the theoretical part. The practical part deals with the use of the diagnostic test Movement Assessment Battery for Children 2, which is designed to identify motor disorders in children. Developmental dyspraxia is very often associated with attention problems so the Test of Attention d2 was used. Difficulty with attention has been confirmed in individuals with impaired physical abilities. There was no significant difference in the overall motor skills between handball players and soccer players. The evaluation of particular components showed significantly better results for girls playing handball in the field of manual dexterity.

Within the last decade, the influence of focus of attention (FOA) instruction on postural control has been an increased interest among researchers (Yeh et al., 2016; McNevin et al., 2013). The general agreement when it comes to the role of FOA has been that adopting an external (EXT) FOA enhances the efficiency of motor programming by strengthening the relationship between movement planning and outcome, when compared to an internal (INT) FOA (see Wulf, 2013). However, increasing evidence suggests that the benefits from an EXT FOA can be mitigated by certain factors (e.g., age, skill level, novelty of the task and task complexity; Becker & Smith, 2013; Emanuel et al., 2008). As such, questions remain as to what form of FOA instruction is best suited for young learners, as FOA research has been criticized for being studied almost exclusively among adults (Agar et al., 2016). Research in this area is particularly sparse as it pertains to FOA in combination with postural control among this younger age group. This is particularly problematic as significant changes in postural control, stability and balance occur during one’s first decade in life (Haas, et al., 1989; Hay & Redon, 1999; Barela et al., 2003). Moreover, there exists some methodological concerns with regard to the lack of consistency of FOA instructions being used during experimentation. This directly influences where participants are guiding their attention and their interpretation of FOA cues (Davids, 2007; Petranek, et al., 2019). Further, the lack of replicability of traditional FOA studies and the increasing number of non-statistically significant findings in this research, calls into question the overall validity, both internal and external, regarding FOA instruction (Becker & Smith, 2013; Lawrence et al., 2011). Therefore, as a series of four complementary studies, the overall aim of this thesis is to further investigate these theoretical as well as procedural gaps. The first study examines which type of FOA instruction is best suited for two groups of young learners (typically developing children between 4-6 and 7-10 years of age) performing a postural control task. Participants will be randomized into either an INT, EXT or CTRL condition, where they will perform a postural control task with different respective visual displays. A force platform will be used to assess participants’ mediolateral centre of pressure (COP) performance, and electromyography (EMG) will be used to assess muscular activation of the participants’ major ankle stabilizers. The primary goal of study one is to investigate the influence of FOA in children by following the most common and traditional of FOA instruction. The second study serves as an extension for the first study. The aim of this study is to specifically investigate the validity and reliability of using FOA instructions, and whether or not the different attentional cues can drive their intended mental focus states. The method of this study is identical to those is Study 1 with a few major exceptions. In this case, two manipulation checks will be added to the procedure in order to assess how participants perceived, comprehended, and acted to their assigned FOA instructional condition. The first manipulation check is embedded in the structure of the trial itself: the comparison of postural control performance with and without visual information, modeled after the technique used in Yeh and colleagues (2016). The second manipulation check will be a retrospective verbal interview inspired by Perreault & French (2016). Finally, the third and fourth studies look to expand the research question from study one and two to different populations of atypically developing young learners who are known to struggle with both attention and postural control. Individuals with ADHD and individuals with DCD have been shown to interpret attentional and postural information differently when compared to age-matched controls. Therefore, the aim of these studies is to compare the differing effects of FOA across neurodiverse populations. Specifically, study three will use a group of young learners (from 4 – 10 years of age) with ADHD and study four will use a group of young learners (from 4 – 10 years of age) with DCD. The only differences in these studies compared to study one will be the lack of an age split and the use of EMG assessment. / Thesis / Master of Science in Kinesiology

Este trabalho estuda o fenômeno de evaporação rápida em jatos de líquidos superaquecidos ou metaestáveis numa região 2D. O fenômeno se inicia, neste caso, quando um jato na fase líquida a alta temperatura e pressão, emerge de um diminuto bocal projetando-se numa câmara de baixa pressão, inferior à pressão de saturação. Durante a evolução do processo, ao cruzar-se a curva de saturação, se observa que o fluido ainda permanece no estado de líquido superaquecido. Então, subitamente o líquido superaquecido muda de fase por meio de uma onda de evaporação oblíqua. Esta mudança de fase transforma o líquido superaquecido numa mistura bifásica com alta velocidade distribuída em várias direções e que se expande com velocidades supersônicas cada vez maiores, até atingir a pressão a jusante, e atravessando antes uma onda de choque. As equações que governam o fenômeno são as equações de conservação da massa, conservação da quantidade de movimento, e conservação da energia, incluindo uma equação de estado precisa. Devido ao fenômeno em estudo estar em regime permanente, um método de diferenças finitas com modelo estacionário e esquema de MacCormack é aplicado. Tendo em vista que este modelo não captura a onda de choque diretamente, um segundo modelo de falso transiente com o esquema de \"shock-capturing\": \"Dispersion-Controlled Dissipative\" (DCD) é desenvolvido e aplicado até atingir o regime permanente. Resultados numéricos com o código ShoWPhasT-2D v2 e testes experimentais foram comparados e os resultados numéricos com código DCD-2D v1 foram analisados. / This study analyses the rapid evaporation of superheated or metastable liquid jets in a two-dimensional region. The phenomenon is triggered, in this case, when a jet in its liquid phase at high temperature and pressure, emerges from a small aperture nozzle and expands into a low pressure chamber, below saturation pressure. During the evolution of the process, after crossing the saturation curve, one observes that the fluid remains in a superheated liquid state. Then, suddenly the superheated liquid changes phase by means of an oblique evaporation wave. This phase change transforms the liquid into a biphasic mixture at high velocity pointing toward different directions, with increasing supersonic velocity as an expansion process takes place to the chamber back pressure, after going through a compression shock wave. The equations which govern this phenomenon are: the equations of conservation of mass, momentum and energy and an equation of state. Due to its steady state process, the numerical simulation is by means of a finite difference method using the McCormack method of Discretization. As this method does not capture shock waves, a second finite difference method is used to reach this task, the method uses the transient equations version of the conservation laws, applying the Dispersion-Controlled Dissipative (DCD) scheme. Numerical results using the code ShoWPhasT-2D v2 and experimental data have been compared, and the numerical results from the DCD-2D v1 have been analysed.

Este trabalho estuda o fenômeno de evaporação rápida em jatos de líquidos superaquecidos ou metaestáveis numa região 2D. O fenômeno se inicia, neste caso, quando um jato na fase líquida a alta temperatura e pressão, emerge de um diminuto bocal projetando-se numa câmara de baixa pressão, inferior à pressão de saturação. Durante a evolução do processo, ao cruzar-se a curva de saturação, se observa que o fluido ainda permanece no estado de líquido superaquecido. Então, subitamente o líquido superaquecido muda de fase por meio de uma onda de evaporação oblíqua. Esta mudança de fase transforma o líquido superaquecido numa mistura bifásica com alta velocidade distribuída em várias direções e que se expande com velocidades supersônicas cada vez maiores, até atingir a pressão a jusante, e atravessando antes uma onda de choque. As equações que governam o fenômeno são as equações de conservação da massa, conservação da quantidade de movimento, e conservação da energia, incluindo uma equação de estado precisa. Devido ao fenômeno em estudo estar em regime permanente, um método de diferenças finitas com modelo estacionário e esquema de MacCormack é aplicado. Tendo em vista que este modelo não captura a onda de choque diretamente, um segundo modelo de falso transiente com o esquema de \"shock-capturing\": \"Dispersion-Controlled Dissipative\" (DCD) é desenvolvido e aplicado até atingir o regime permanente. Resultados numéricos com o código ShoWPhasT-2D v2 e testes experimentais foram comparados e os resultados numéricos com código DCD-2D v1 foram analisados. / This study analyses the rapid evaporation of superheated or metastable liquid jets in a two-dimensional region. The phenomenon is triggered, in this case, when a jet in its liquid phase at high temperature and pressure, emerges from a small aperture nozzle and expands into a low pressure chamber, below saturation pressure. During the evolution of the process, after crossing the saturation curve, one observes that the fluid remains in a superheated liquid state. Then, suddenly the superheated liquid changes phase by means of an oblique evaporation wave. This phase change transforms the liquid into a biphasic mixture at high velocity pointing toward different directions, with increasing supersonic velocity as an expansion process takes place to the chamber back pressure, after going through a compression shock wave. The equations which govern this phenomenon are: the equations of conservation of mass, momentum and energy and an equation of state. Due to its steady state process, the numerical simulation is by means of a finite difference method using the McCormack method of Discretization. As this method does not capture shock waves, a second finite difference method is used to reach this task, the method uses the transient equations version of the conservation laws, applying the Dispersion-Controlled Dissipative (DCD) scheme. Numerical results using the code ShoWPhasT-2D v2 and experimental data have been compared, and the numerical results from the DCD-2D v1 have been analysed.

Title: Evaluation of motor skills level in children of the primary education of selected Prague elementary schools Objectives: The main aim of the study was to evaluate current level of motor skills of primary education children of selected Prague elementary schools using standardized assessment battery MABC-2. A partial goal of the study was to compare the level achieved in the MABC-2 test with the data acquired through the questionnaire survey regarding physical activities of participating responders. (n = 134). Methods: A total number of 134 responders (60 girls and 74 boys) aged from 7 to 12 years from two selected Prague elementary schools participated in the research. The level of motor skills of all participants was examined using a standardized assessment battery MABC- 2. The testing was carried out in the form of field research during physical education lessons at selected schools. A questionnaire designed specifically for the purpose of this study, subsequently completed by legal representatives of the responders, was used for the orientation examination of the physical behaviour of the participants. The data from the questionnaire survey was subsequently compared with the level achieved in the MABC-2 test. MS Excel 2010 was used to interpret the results and to process the data...

Contexte : Au cours de la dernière décennie, le nombre de personnes en attente d’une transplantation cardiaque a augmenté d’environ 25%, tandis que le nombre de greffes effectuées chaque année est resté stable. Le taux de décès des patients en attente d’une greffe cardiaque est d’environ 15-20%. Le don d’organe suite à un décès cardiocirculatoire (DDC) est une alternative au don après décès neurologique (DDN) qui a permis d’augmenter le nombre d’organes disponibles comme les poumons, les reins et les foies. Compte tenu de la survenue d’une mort cardiovasculaire dans les protocoles DDC, le cœur est rarement greffé à cause des dommages infligés durant la période d’ischémie chaude. Notre équipe a précédemment démontré que l’utilisation du Celastrol, ainsi que notre analogue synthétique inhibiteur de la HSP90 ont des effets cardioprotecteurs, quand administrés au moment de la reperfusion dans des modèles in vitro de culture cellulaire et ex vivo dans des cœurs de rats montés sur le système de perfusion Langendorff. L’objectif est d’évaluer les mécanismes cardioprotecteurs rapides d’une nouvelle formulation de l’inhibiteur HSP90, et de comprendre l’efficacité de ce nouveau composé synthétique sur deux lignées de cellules : les cardiomyoblastes H9c2 issus de rats et les cardiomyocytes dérivés de cellules souches pluripotentes humaines (iPSC-CMs). Méthodes/Résultats : Les cellules H9c2 et iPSC-CMs ont été cultivées. La signalisation cellulaire a été analysée par western blot pour évaluer le niveau d’activation de ces différentes voies. Suite à l’optimisation des conditions pour les cellules iPSC-CMs, les deux lignées cellulaires ont été mises en condition ischémique (sans glucose, 95% N2, 5% CO2) durant la nuit, puis reperfusées, en conditions normales, avec différentes concentrations de l’inhibiteur HSP90. La viabilité cellulaire ainsi que l’ouverture des pores mitochondriaux (mPTP) ont été évaluées à l’aide de kits d’analyses, la production de radicaux libres d’oxygène à l’aide de kits de fluorescence et l’expression des ARN messagers de gènes antioxydants à l’aide de la réaction en chaîne par polymérase (PCR). Les résultats ont montré une augmentation de l’activation des voies cytoprotectrices quand les deux lignées cellulaires étaient traitées à la concentration 10-6M du composé sans stress 4 ischémique : augmentation de HO-1 and HSP-70 dans les 30 premières minutes et AKT et ERK après 1 heure de traitement et 3 heures de récupération. Contrairement à nos attentes, le traitement au moment de la reperfusion à la concentration 10-6M a montré une diminution de la viabilité des cellules, alors que la concentration 10-7M l’a augmenté. À une concentration de 10- 7M, il y a eu diminution de la production de radicaux libres comparativement au groupe témoin. Comme attendu, cette concentration a aussi démontré une diminution de l’ouverture des mPTP. Tous ces résultats ont été observés, autant dans les cellules humaines que celles de rats. Une évaluation préliminaire de l’expression des gènes antioxydants dans les cellules H9c2 a seulement montré une augmentation de l’expression des gènes CAT et HO-1. Conclusion : Notre groupe de recherche a précédemment démontré l’efficacité des composés issus du Celastrol sur la réduction des dommages myocardiques dus à la reperfusion dans les modèles d’ischémie, incluant l’infarctus du myocarde et la donation après décès cardiocirculatoire. Ces expériences ont montré les effets bénéfiques du nouveau composé synthétique sur l’expression des gènes antioxydants, et sur l’activation d’une série de voies cytoprotectrices permettant la stabilisation de la membrane mitochondriale, réduisant aussi la production de radicaux libres, et améliorant ultimement la survie cellulaire. Des études supplémentaires sont en cours afin d’améliorer la compréhension des modes d’action, des mécanismes et des dosages optimaux du médicament, ce qui nous permettra de commencer les essais sur animaux dans le but d’introduire cette molécule en clinique dans le contexte de don d’organes. / Background: During the last decade, the number of people waiting for a cardiac transplantation has increased by about 25%, while the number of yearly transplant surgeries performed has remained steady. The death rate of patients awaiting heart transplant is about 15-20%. Organ donation after circulatory death (DCD) is an alternative to donation after neurological death (DND) that has allowed to increase the number of available organs like lungs, livers, and kidneys. However, because of the cardiac death in DCD protocols, the heart is rarely used because of the injuries suffered by the warm ischemia period. Our group has previously shown that Celastrol, along with a synthetic HSP90 inhibitor analog, have cardioprotective effects when given as postconditioning agents at the moment of reperfusion in an in vitro model on cellular cultures and an ex vivo model on rat hearts mounted on a Langendorff perfusion system. The objective is to evaluate the rapid cardioprotective mechanisms of a novel formulation of the HSP90 inhibitor compound, and to understand the efficacy of this new synthetic compound on two cell lines: rat H9c2 cardiomyoblasts and human induced pluripotent stem cell-derived cardiomyocytes (iPSCCMs). Methods/Results: H9c2 rat cardiomyoblasts and human iPSC-CMs were cultured. Cell signaling was analyzed by western blot to evaluate pathway activations. Both cell lines were put in ischemic conditions (no glucose, 95% N2, 5% CO2) overnight, then reperfused (normal conditions) with different concentrations of HSP90i after optimizing the human iPSC-CMs’ stress experiment. Cell viability and mitochondrial permeability transition pore (mPTP) opening were evaluated using assays, oxygen-free radical production by fluorescence assay and antioxidant gene messenger RNA expression via polymerase chain reaction (PCR). Results showed an increase in cytoprotective pathway activation when both cell lines were treated with 10-6M of the compound without any stress: HO-1 and HSP-70 in the first 30 minutes while AKT and ERK after 1 hour of treatment and 3 hours of recuperation. Interestingly, treatment with the compound at 10-6M at the moment of reperfusion showed decreased viability of the cells while 10-7M improved it. Free radical production was also decreased at a concentration of 10-7M 6 when compared to the baseline, and as expected, the compound also decreased mPTP opening. These results were seen in both human and rat cell lines. Preliminary evaluation of antioxidant gene expression in H9c2 cells only showed an increase in the expression of the cytoprotective CAT and HO-1 genes. Conclusion: Our research group has previously demonstrated the efficacy of Celastrol compounds in reducing reperfusion damage in myocardial ischemia models, including myocardial infarction and donation after circulatory death. These experiments have shown that the beneficial effects of this new synthetic compound include the expression of antioxidant genes and the launching of a series of cytoprotective pathways that stabilize the mitochondrial membrane, reduce free radical production, and improve cell survival. Additional studies to fully understand the mode of action, the mechanisms and the optimal dosages are underway to allow us to move to animal trials in order to ultimately introduce the molecule in the clinical field in the context of organ donation.

Irish agriculture is becoming increasingly regulated, with restrictions on fertiliser application rates and stocking rates to reduce nitrate (NO₀⁻) leaching losses. However these regulations have been, to date, based on minimal field research. The purpose of this study was to determine the actual leaching losses of nitrate from Irish dairy pasture at a range of stocking rates, and to investigate the effectiveness of the nitrification inhibitor DCD at reducing nitrate leaching losses where these are deemed excessive. In grazed pastures, a major source of leached nitrate is the urine patch, where a high rate of N is applied in one application. This trial recorded the losses from urine and non-urine areas of pasture separately. Nitrate leaching losses from three soils were recorded using lysimeters at Johnstown Castle, Co. Wexford, over two years. Total nitrate losses were higher from the freely drained Clonakilty and Elton soils than from the heavy Rathangan soil. Mean nitrate losses from urine patches ranged from 16 - 233 kg nitrate-N / ha⁻¹, and were reduced by up to 53% when DCD was applied. DCD also reduced peak and mean nitrate-N concentrations in many cases. In addition, DCD halved the nitrous oxide (N₂O) emission factor on the Rathangan soil, caused increases in pasture N content, and increased herbage yield in some treatments. The distribution of urine patches under dairy grazing was recorded using GPS at Kilworth, Co. Cork. Cows were also found to deposit 0.359 urine patches per grazing hour. A model was produced to predict field-scale nitrate leaching losses from dairy pasture at a range of stocking rates. At 2.94 cows per hectare, the highest stocking rate, annual field N loss was below 34 kg nitrate-N ha⁻¹, mean drainage N concentrations were below 5.65 mg nitrate-N L⁻¹ (the EU drinking water guideline value), and the worst-case-scenario autumn peak concentration did not exceed 21.55 mg nitrate-N L⁻¹ (above the EU Maximum Allowable Concentration (MAC) but below the World Health Organisation (WHO) drinking water limit). DCD reduced total annual field N loss by 21% (a conservative estimate), and also reduced mean and peak nitrate concentrations. Provided fertiliser application rates are at or below 291 kg N ha⁻¹, and based on current legislative values for drinking water quality, this trial does not support any blanket restrictions on the stocking rate of Irish dairy farms. However where particularly high water quality is required, DCD shows potential as a useful tool to achieve low nitrate concentrations.

[ES] Antecedentes: El virus de la gripe es una de las principales causas de infecciones respiratorias a nivel mundial, provocando epidemias estacionales con un impacto significativo en la salud pública y en la economía. A pesar de más de mil millones de casos anuales en el mundo, algunas personas expuestas al virus permanecen asintomáticas. La causa de esta resistencia no se ha aclarado, pero comprenderla podría conducir a nuevas estrategias preventivas y terapéuticas. En un estudio previo de nuestro laboratorio se identificó un péptido antimicrobiano humano (AMP), la dermicidina, a partir de genotecas de individuos asintomáticos, sugiriendo un posible papel antiviral. Esta tesis analiza si las diferencias de susceptibilidad a la gripe están relacionadas con la producción de dermicidina. Objetivos: Este trabajo tiene como objetivo confirmar y caracterizar la actividad antiviral de la dermicidina contra el virus de la gripe, centrándose en los subtipos H1N1 y H3N2. Investiga también el mecanismo de acción del péptido, su papel en la susceptibilidad a padecer los síntomas de gripe y su producción en las vías respiratorias humanas. Además, evalúa el potencial terapéutico de la dermicidina, incluyendo su citotoxicidad, tolerabilidad y eficacia en un modelo animal. Métodos: Se evaluó la actividad antiviral de la dermicidina y sus derivados mediante ensayos de inhibición de hemaglutinación (HAI) y ensayo de placa contra siete cepas del virus de la gripe en cultivos celulares. Se estudió el mecanismo de acción mediante ensayos de afinidad, acoplamiento molecular y simulaciones dinámicas. Los niveles de dermicidina en muestras humanas se analizaron con ELISA, y se realizaron análisis genéticos comparativos de individuos sintomáticos y asintomáticos mediante secuenciación PacBio y VarScan. La citotoxicidad se evaluó con el ensayo MTT, y la eficacia terapéutica se probó en ratones Balb/c analizando peso, síntomas, carga viral y producción de citoquinas inflamatorias. Resultados y discusión: Esta tesis caracteriza la actividad antiviral de la dermicidina, identificando DCD-1L como el péptido más efectivo, con concentraciones inhibitorias de 81-254 µM contra los subtipos H1N1 y H3N2. La dermicidina se une a la zona del tallo de la hemaglutinina (HA), bloqueando la etapa inicial de la infección, un mecanismo conservado que podría ser eficaz contra otros virus con HA, como el coronavirus humano OC43 y el virus del sarampión. La dermicidina se produce en las rutas de entrada viral en humanos (lágrimas, saliva y secreciones nasofaríngeas), con mayores niveles en individuos asintomáticos, lo que podría explicar su resistencia. Este péptido también se sobreproduce en respuesta a infecciones respiratorias, lo que confirma su papel en la respuesta inmune innata. En el análisis genético no encontraron variantes asociadas con la resistencia a los síntomas, sugiriendo que la mayor producción de dermicidina es clave. Estudios en animales confirmaron que DCD-1L es seguro, bien tolerado y eficaz, comparable al zanamivir cuando se co-incuba con el virus. Conclusión: La susceptibilidad a los síntomas de la gripe está parcialmente asociada con la producción de dermicidina en las rutas de entrada de virus respiratorios. Los resultados destacan su potencial uso como agente terapéutico para tratar y prevenir la gripe y otras infecciones virales respiratorias. / [CA] Antecedents: El virus de la grip és una de les principals causes d'infeccions respiratòries, provocant epidèmies estacionals amb un impacte significatiu en la salut pública i en l'economia. Tot i més de mil milions de casos anuals en tot el món, algunes persones exposades al virus romanen asimptomàtiques. La causa d'aquesta resistència no s'ha aclarit, però comprendre-la podria portar a noves estratègies preventives i terapèutiques. Un estudi previ del nostre laboratori va identificar un pèptid antimicrobià humà (AMP), la dermicidina, en genoteques d'individus asimptomàtics, suggerint un possible paper antiviral. Aquesta tesi analitza si les diferències de susceptibilitat a la grip estan relacionades amb la producció de dermicidina. Objectius: Aquest treball té com a objectiu confirmar i caracteritzar l'activitat antiviral de la dermicidina contra el virus de la grip, centrant-se en els subtipus H1N1 i H3N2. Investiga també el mecanisme d'acció del pèptid, el seu paper en la susceptibilitat als símptomes i la seua producció en les vies respiratòries humanes. A més, avalua el potencial terapèutic de la dermicidina, incloent-hi la seua citotoxicitat, tolerabilitat i eficàcia en un model animal. Mètodes: Es van avaluar els efectes antivirals de la dermicidina i els seus derivats mitjançant assajos d'inhibició de l'hemaglutinació (HAI) i de plaques contra set soques del virus de la grip en cultius cel·lulars. Es va estudiar el mecanisme d'acció amb assajos d'afinitat, acoblament molecular i simulacions dinàmiques. Els nivells de dermicidina en mostres humanes es van analitzar amb ELISA, i es van fer anàlisis genètiques comparatives d'individus simptomàtics i asimptomàtics mitjançant seqüenciació PacBio i VarScan. La citotoxicitat es va avaluar amb l'assaig MTT, i l'eficàcia terapèutica es va provar en ratolins Balb/c analitzant pes, símptomes, càrrega viral i citoquines inflamatòries. Resultats i Discussió: La tesi caracteritza l'activitat antiviral de la dermicidina, identificant DCD-1L com el pèptid més efectiu, amb concentracions inhibidores de 81-254 µM contra els subtipus H1N1 i H3N2. La dermicidina s'uneix a la zona del tronc de l'hemaglutinina (HA), bloquejant l'etapa inicial de la infecció, un mecanisme conservat que podria ser eficaç contra altres virus amb HA, com el coronavirus humà OC43 i el virus del xarampió. La dermicidina es produeix en les vies d'entrada viral en humans (llàgrimes, saliva i secrecions nasofaringees), amb nivells més alts en individus asimptomàtics, cosa que podria explicar la seua resistència. Aquest pèptid també es sobreprodueix en resposta a infeccions respiratòries, confirmant el seu paper en la resposta immune innata. L'anàlisi genètica no va trobar variants associades amb la resistència als símptomes, suggerint que la major producció de dermicidina és clau. Els estudis en animals van confirmar que DCD-1L és segur, ben tolerat i eficaç, comparable al zanamivir quan es co-incuba amb el virus. Conclusió: La susceptibilitat a patir els símptomes de la grip està parcialment associada amb la producció de dermicidina en les vies d'entrada de virus respiratòries. Els resultats destaquen el seu potencial ús com a agent terapèutic per a tractar i prevenir la grip i altres infeccions virals respiratòries. / [EN] Background: Influenza virus is one of the major causes of respiratory infections, leading to seasonal epidemics with significant economic and public health impacts. Despite over a billion cases annually worldwide, some individuals exposed to the virus remain asymptomatic. The basis for this resistance is unclear, but understanding it could lead to new preventive and therapeutic strategies. A previous study from our lab identified a human antimicrobial peptide (AMP), dermcidin, from DNA libraries of asymptomatic individuals, suggesting a potential antiviral role. This thesis explores whether susceptibility differences to influenza are linked to dermcidin production. Objectives: This research aims to confirm and characterize the antiviral activity of dermcidin against influenza virus, focusing on two main subtypes (H1N1 and H3N2). It also investigates the peptide's mechanism of action, its role in susceptibility to symptoms, and its production in human respiratory pathways. Additionally, it evaluates dermcidin's potential as a therapeutic agent, including its cytotoxicity, tolerability, and efficacy in an animal model. Methods: The antiviral effects of dermcidin and derived peptides were tested using hemagglutination inhibition (HAI) and plaque inhibition assays against seven influenza virus strains in cell culture. Mechanisms of action were studied via affinity assays, molecular docking, and dynamic simulations. Dermcidin levels in human samples were assessed using ELISA, with comparative genetic analyses of symptomatic and asymptomatic individuals conducted using PacBio sequencing and VarScan. Cytotoxicity was tested by MTT assay, and therapeutic efficacy was evaluated in Balb/c mice by monitoring body weight, symptoms, viral load, and inflammatory cytokine levels. Results and Discussion: This thesis characterizes the antiviral activity of dermcidin, identifying DCD-1L as the most effective peptide, with inhibitory concentrations of 81-254 µM against H1N1 and H3N2 subtypes. Dermcidin binds to the hemagglutinin (HA) stalk zone, blocking the initial infection stage, a conserved mechanism potentially effective against other HA-expressing viruses, including human coronavirus OC43 and measles virus. Dermcidin is naturally produced in human viral entry routes such as tears, saliva, and nasopharyngeal secretions, with asymptomatic individuals secreting higher amounts in the nasopharynx, which may explain their resistance to symptoms. The peptide is overproduced in response to various respiratory viral infections, supporting its role in the innate immune response. Genetic analysis showed no specific variants associated with symptom resistance, suggesting that higher dermcidin production underlies this trait. Animal model studies confirmed DCD-1L's safety, tolerability, and efficacy, comparable to zanamivir when co-incubated with the virus. Conclusion: Susceptibility to influenza symptoms is partly associated with dermcidin production in respiratory viral entry pathways. The findings highlight dermcidin's potential as a novel therapeutic agent for influenza and other respiratory viral diseases, addressing the need for new strategies against these infections. / Corell Escuin, P. (2025). Characterization of the antiviral activity of dermcidin in vitro and in vivo, and its potential role against respiratory viral infections [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/214795