Se describe la evidencia actual del efecto del SARS-CoV-2 a nivel de tejido renal. Se realizó una revisión narrativa de los artículos publicados en SCOPUS y PUBMED hasta septiembre de 2020. Los resultados se dividieron en las siguientes secciones: evidencia del efecto directo del virus en el riñón, mecanismos de invasión celular, mecanismos de injuria celular y las potenciales implicaciones terapéuticas de estos hallazgos. El SARS-CoV-2 invade las células del túbulo proximal y los podocitos, a través del receptor ECA-2. La invasión y replicación viral podrían producir daño mediante un efecto citopático directo aunado a un daño mediado por la respuesta inmune. Debido a la expresión celular de ECA-2, se ha propuesto a los Inhibidores del Sistema Renina–Angiotensina–Aldosterona como un potencial tratamiento contra la COVID-19. Sin embargo, a la fecha, la evidencia no apoya su uso. / We describe evidence on SARS-CoV-2 effect on the kidney. We carried a narrative review of articles published in SCOPUS and PUBMED until September 2020. The results were divided into six topics: evidence of direct effect of virus on the kidney, mechanisms of cellular invasion, mechanisms of kidney injury, and potential therapeutic implications. SARS-Cov-2 gains access to proximal tubule cells and podocytes via ACE-2 receptors. Viral invasion and replication may induce kidney damage through a direct cytopathic effect and immune-mediated damage. Due to ACE-2 cellular expression, Renin–Angiotensin–Aldosterone System Inhibitors have been proposed as potential treatment for COVID-19. However, current evidence does not support its therapeutic use. / Trabajo de investigación

Introduction The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARSCoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever. Materials and methods A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed. Results 464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARSCoV-2, both with (12.50%). The presence of polyarthralgias in hands (43.75%, p<0.01) and feet (31.25%, p = 0.05) were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM (11.45%, p<0.01). The rest of the symptoms were similar among all the study groups. Conclusion SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens. Copyright: / Revisión por pares

Cette thèse s’inscrit dans le cadre général de la dépollution d’effluents gazeux faiblement chargés en Composés Organiques Volatils (COV). L’étude concerne l'oxydation de trois COV cibles (méthane, propène, et toluène) dans l'air à la pression atmosphérique dans d'une part un réacteur plasma de décharge à barrière diélectrique (DBD) pulsée et un réacteur catalytique utilisés séparément et d'autre part, dans un réacteur hybride associant le réacteur plasma aux catalyseurs dans deux configurations: le catalyseur au coeur de la décharge et le catalyseur en post-décharge. Les catalyseurs sont à base de Pd, Mn, Cu, et Co supportés sur des billes de Al2O3. Ils ont été caractérisés par ICP-OES, TEM/EDX, XRD, XPS, et DRIFTS. L’efficacité de conversion des COV, la sélectivité en CO/CO2, ainsi que la nature et les concentrations des produits formés pour les trois molécules avec les trois systèmes ont été étudiées en fonction de la température du gaz, de l'énergie injectée, de la concentration des COV, de la taille du support, du type de métal et sa teneur, et de la vitesse volumique horaire. Dans tous les cas, l’activation des catalyseurs à basse température a été démontrée quand ces derniers sont couplés au plasma et les principaux produits de réaction identifiés et quantifiés par spectroscopie infrarouge à transformée de Fourier. Le couplage plasma-catalyseur améliore de façon significative l’efficacité de conversion du méthane, du propène, et du toluène dans l’air ainsi que la sélectivité en sous-produits. L'effet de synergie entre le plasma et les catalyseurs pour la conversion des COV a été démontré dès lors que le plasma est généré directement au sein du réacteur catalytique. / The focus of this thesis is the application of non-thermal plasma and catalysis in chemical processing, in particular for the removal of Volatile Organic Compounds (VOC) diluted in air. In a first part, the oxidation of three pollutants (methane, propene, and toluene) is studied experimentally in a pulsed dielectric barrier discharge (DBD) reactor and in a catalyst reactor working independently. In a second part, a hybrid plasma-catalyst reactor either in a single-stage or in a two-stages configuration, in which the catalyst is located inside or downstream from the plasma reactor, respectively. Catalyst materials based on Pd, Mn, Cu, and Co supported on alumina beads were tested and characterized by ICP-OES, TEM/EDX, XRD, XPS, and DRIFTS. Products were analyzed and quantified by infrared spectroscopy. Achieved VOCs removal efficiencies and CO/CO2 selectivity, as well as nature and concentrations of the formed products, were evaluated as function of many factors, particularly the specific input energy, the gas temperature, the initial VOCs concentration, the nature of catalyst (size support, metal loading), and the hourly space velocity. It has been successfully demonstrated that the combination of plasma and catalyst in the both configurations has many benefits compared to traditional thermal-catalysis and plasma alone treatment including a lowering of the catalyst operating temperature, an improvement of the conversion of VOCs at similar temperatures, and a better end-products selectivity and energy efficiency. The mutual interaction lead to a synergistic effect in plasma-catalysis especially when the discharge is in direct contact with the catalyst whatever the VOCs studied.

Background: The COVID-19 pandemic is caused by the SARS-CoV-2 virus, which enter the host cells through interactions between the receptor-binding domain (RBD) on the S-protein and the ACE-2 receptor on the host cell. A novel type of vaccine strategy is peptide vaccines, with great potential as a faster and more selective approach to conventional vaccine development. This study focuses on the possibility of generating an antibody response through synthetic peptides harboring B cell epitopes.  Aim: This project aims to investigate the potential of immunogenic peptides to generate an antibody response when used as synthetically produced peptides. As proof-of-concept, the project studies the interactions between previously identified monoclonal antibodies with defined B cell epitopes and the corresponding peptide sequences.  Method: The interactions are evaluated by different ELISA experiments. The candidate peptides are additionally investigated on their binding to polyclonal serum with established S reactive antibodies. Furthermore, the project includes synthesis of one peptide by solid phase peptide synthesis. Results: The ELISA experiments presented no interaction between the synthetic peptides and the monoclonal antibodies or human sera.  Conclusion: The project fulfilled its aim to study the interaction between the B cell epitopes and the monoclonal antibodies. However, no binding was observed. Despite the many advantages in production and stability, development of B cell epitope vaccines come with many challenges. Future will entail if synthetic peptides harboring B cell epitopes can be used as vaccines, or if peptide vaccines will be a focus when a T cell response is to be induced.

No description available.

<p>  </p> <p>Designing and developing a diagnostic technology that is capable of highly sensitive and specific, multiplexed, high-throughput, and quantitative biomarker assays for disease diagnosis and progression is of the upmost importance in modern medicine and patient care. Current diagnostic assays capable of multiplexed and high-throughput analysis include mass spectrometry, electrochemistry, polymerase chain reaction (PCR), and fluorescence-based techniques, however, these techniques suffer from a lack in sensitivity, false responses, or extensive sample processing that are detrimental to clinical diagnostics. To overcome these sensitivity challenges, the field of nanoplasmonics has become utilized when developing diagnostic assays. Plasmonic-based diagnostic tests utilize the unique optical, chemical, and physical property of nanoparticles to increase the sensitivity of the assay. In this dissertation, novel diagnostic platforms that utilize nanoparticles and their localized surface plasmon resonance (LSPR) property will be introduced. LSPR is an optical property in noble metallic nanoparticles that is referred to as the collective oscillation of free electrons upon light irradiation. It is highly dependent on the shape, size, and dielectric constant (refractive index) of the surrounding medium of the nanoparticle and LSPR sensing is based on a change in these properties. In this dissertation, the LSPR property is utilized to fabricate nanoplasmonic-based diagnostic platforms that are capable of multiplexed and high-throughput biomarker assays, with high sensitivity and specificity. The work presented in this dissertation is presented as six chapters, (1) Introduction. (2) Methods, (3) Fabrication of a LSPR-based multiplexed and high-throughput biosensor platform and its application in performing microRNA assays for the diagnosis of bladder cancer. In this chapter, the advancement of single-plex solid state LSPR-based biosensors into a multiplexed and high-throughput diagnostic biosensor platform is reported for the first time. The diagnostic biosensor platform is first fabricated utilizing different gold nanoparticles (spherical nanoparticles, nanorods, and triangular nanoprisms), and then with the gold triangular nanoprisms as the nanoparticle of choice, microRNA assays were performed. The developed biosensor platform is capable of assaying five different types of microRNAs simultaneously at an attomolar limit of detection. Additionally, five microRNA were assayed in 20-bladder cancer patient plasma samples. (4) Development/optimization of the biosensor platform presented in Chapter 3 for the detection of COVID-19 biomarkers. In this chapter, the biosensor platform utilized in Chapter 3 was designed to assay 10 different COVID-19 specific biomarkers from three classes (six viral nucleic acid gene sequences, two spike protein subunits, and two antibodies) with limit of detections in the attomolar range and with high specificity. The high-throughput capability of the biosensor platform was advanced, with the platform performing analysis of a single biomarker in 92 patient samples simultaneously. Additionally, the biomarker platform was utilized to assay all 10 biomarkers in a total of 80 COVID-19 patient samples.  (5) Further optimization of the biosensor platform for the development of a highly specific antibody detection test for COVID-19. During the COVID-19 pandemic, knowledge was gained on the specificity of antibodies produced against COVID-19. In this chapter, that knowledge was applied towards the optimization of the biosensor platform presented in Chapter 4 in order to assay SARS-CoV-2 neutralizing antibody IgG. The optimization of the biosensor platform included the size of the gold triangular nanoprisms and the receptor molecule of choice. The biosensor platform assayed this highly specific COVID-19 IgG antibody with a limit of detection as low as 30.0 attomolar with high specificity and no cross reactivity. Additionally, as a proof of concept, the biosensor platform was utilized in a high-throughput format to assay SARS-CoV-2 IgG in a large cohort of 121 COVID-19 patient samples simultaneously. (6) Advancement of the biosensor platform from a 96-well plate to a 384-well plate and its application in assaying microRNA for early diagnosis of pancreatic cancer. In this chapter, the high-throughput capabilities of the biosensor platform presented in Chapters 3-5 was expanded by increasing the sensor amount in one platform from 92 to 359. The 384-well plate biosensor platform was designed, optimized, and utilized to perform microRNA assays for early-stage pancreatic cancer diagnosis. The optimization of the biosensor platform included the manipulation of LSPR-based parameters and the -ssDNA receptor molecule in order to obtain low limit of detections (high sensitivity). Additionally, the biosensor platform assayed two microRNA in a large cohort (n=110) of pancreatic cancer and chronic pancreatitis patient samples. </p>

Det har gått över ett år sedan viruset Covid-19 klassificerades som en pandemi i världen. Händelsen har förändrat vårt sätt att leva, på ett sätt som vi inte hade en aning om innan. Restriktioner, rekommendationer och nya lagändringar har abrupt implementerats i samhället. Genom att stanna hemma från vardagliga aktiviteter som skola och jobb, liksom att begränsa antalet personer i sin närhet, skulle sociala möten minska och viruset därmed hämmas. Viruset finns dock fortfarande omkring oss och vi fortsätter att anpassa oss. Syftet med studien är att undersöka hur behovet av offentliga platser har förändrats under covid-19-pandemin och om dessa behov möts av stadsutformningen i Stockholm. Vidare undersöks om det är möjligt att skapa en tät stadsbebyggelse som främjar social hållbarhet och som fungerar i kristider. Stadsplaneringsideal förändras över tid och i detta nu ligger betoningen på mångfald, hållbarhet och stadsmässighet. Områdena Hammarby Sjöstad, Norra Djurgårdsstaden och Liljeholmskajen i Stockholm ligger till grund för undersökningen eftersom dessa är uppförda under samma tid och präglas av liknande stadsplaneringsideal. Metoden som har använts i studien utgörs av enkäter, en kvalitativ områdesanalys och intervjuer med boende i respektive område. Studien visar att varken de nationella rekommendationerna eller stadens egna visioner för utformning av nya stadsbyggnadsprojekt har beaktats någon högre grad i de undersökta områdena. Låg prioritering av grönområden och parker är ett exempel, ytor för barn är ett annat, vilket framkommer av de kvalitativa områdesanalyserna. Enkätresultatet från områdesundersökningen stöder tidigare studier som visar att människor använder rekreationsområden, som parker och grönområden, i större utsträckning under pandemin. Utbudet av service i närområdet verkar också spela en större roll under pandemin. En slutsats är att den upplevda tätheten bör prioriteras i stadsplaneringen för att skapa socialt hållbara stadsmiljöer. Genom att inkludera multifunktionalitet i formandet av allmänna platser tror vi att temporära samhällsförändringar och krav lättare kan mötas. / It has been over a year since the cov-sars-19 virus was categorised as a pandemic across the world. It has changed our way of living in a way we did not see coming. Restrictions, recommendations and laws were rapidly introduced in society. By staying home from everyday activities such as school and work, as well as reducing the amount of people one meets, gatherings would be reduced, and the virus could be fought. Yet, we are still trying to adapt. The aim of this study is to analyse the new needs of public spaces during the pandemic and whether the built environment in Stockholm meets those expectations. Further, it seeks to examine whether it is possible to create an urban agglomeration while focusing on a socially sustainable environment that would also be suitable during times of crisis. City planning changes over time and forms new ideals and principles. Currently, diversity, sustainability, and urbanity are important ways of thinking about city planning. Therefore, this study has focused on three areas in Stockholm: Hammarby Sjöstad, The Stockholm Royal Seaport, and Liljeholmskajen. Those areas are all the result of the same way of planning. The methods used in this study are questionnaires for each area, as well as a qualitative analysis and interviews. Despite the existence of national recommendations and visions for planning new urban areas, it appears that there is a difference in how they have been taken into consideration for the areas in this study. Between the areas, there is an obvious difference in the implementation of green areas, playgrounds, and parks, among other things. This observation emerges from the results of the questionnaires, as well as from the theory. A distinct pattern of much greater use by residents of recreational areas such as parks and other green spaces than before the pandemic can also be observed. This is a result of needing spaces in the city where distancing is possible. The neighborhood and its supply of services tends to play a bigger role during the pandemic. The study concludes that to be able to create socially sustainable environments, it is important to focus on the perceived density in city planning. By incorporating multifunctionality in the form of public spaces, we believe temporary changes and demands can more easily be met.

Problématique : Il existe différents types d’unités de soins intensifs (USI). En fonction des besoins des patients, les USI fournissent des niveaux de soins plus ou moins complexes afin de répondre à des situations de soins spécifiques. Les patients peuvent être amenés à être transférés d'une USI à une autre afin que les soins prodigués soient axés sur les besoins de santé de la clientèle. Dans le contexte de la pandémie causé par le SARS-CoV-2 (COVID-19), des mesures sanitaires ont été mises en place par le gouvernement afin d’en contrôler la transmission. Ces restrictions comprenaient entre autres la limitation des visites en milieu de soins, voire à certains moments, une interdiction absolue. Ces restrictions ont eu un impact direct sur la présence et l'accompagnement des proches en USI. Cette limitation peut notamment avoir une influence sur la manière dont les proches, les professionnels et les gestionnaires des unités de soins intensifs vivent le processus de transfert. Objectif: L’objectif de cette étude est d’évaluer la perception du vécu des familles, des équipes cliniques et des gestionnaires de proximité concernant les transferts inter hospitaliers d’usagers hospitalisés sur une unité de soins intensifs au CHUM. Méthodes : Une étude prospective exploratoire à devis mixte a été réalisée entre juin 2022 et octobre 2022. Huit membres de l'entourage de patients ayant été transférés sur une des deux unités de soins intensifs généraux du CHUM et un responsable clinico-administratif de l'USI générale d’un centre universitaire ont été recrutés et rencontrés lors d'une entrevue semi-dirigée. Dix-sept professionnelles ont répondu à un questionnaire quantitatif. Résultats : Cette étude a croisé la perception du vécu des proches concernant le transfert de patients entre USI dans un centre hospitalier universitaire au Québec dans le contexte de la COVID-19 avec celle des professionnels de soins. Tant les proches que les professionnels ont souligné l’importance de l’accès à l’information sur les circonstances du transfert. De plus, ils soulignent que le proche doit posséder l’information avant que le transfert ne soit réalisé. Les méthodes privilégiées tant par les proches que par les professionnels concernant le transfert d’information sur les circonstances du transfert sont en présentiel (n=14; 93.3%) ainsi que téléphonique (n=7; 46.7%). Conclusion : Les membres de la famille et les professionnels de la santé conviennent que la communication et le transfert d'information sont importants pour que le membre de la famille ait une expérience qui qui génère une perception positive pour le membre de la famille. Aligner et uniformiser le processus de transfert peut être une façon de l'améliorer. La présence d’une personne-ressource au sein de l’équipe de soins pour accueillir, accompagner et guider le membre de la famille après le transfert du patient vers l'établissement d'accueil est une solution proposée par les participants de cette étude. / Problem: There are different types of intensive care units (ICUs). Depending on the needs of patients, ICUs provide complex levels of care in order to respond to specific care situations. Patients may need to be transferred from one ICU to another to ensure adequate care. In the context of the SARS-CoV-2 (COVID-19) pandemic, health measures have been put in place by the government to control transmission. These restrictions include limiting visits to health care settings, and at times even an absolute ban. This ban has had a direct impact on the presence and support of relatives in the ICU. This limitation can have an influence on the way relatives, professionals and managers of intensive care units experience the transfer process. Objective: The objective of this study is to evaluate the perception of the experiences of families, clinical teams and community managers regarding interhospital transfers of hospitalized users to an intensive care unit at the CHUM. Methods: A mixed exploratory prospective study with a mixed design was carried out between June 2022 and October 2022. Eight members of the entourage of patients who had been transferred to one of the two general intensive care units of the CHUM and a clinical-administrative manager of the ICU general of a university center were recruited to meet during a semi-structured interview. Seventeen professionals answered a quantitative questionnaire. Results: This study crossed the perception of the experiences of loved ones, regarding the transfer of patients between ICU in a university hospital in Quebec in the context of COVID-19. Relatives and professionals corroborate in the perception that it is important that the relative has information about the circumstances of the transfer and that the relative must have the information before the transfer is carried out. The methods preferred by both relatives and professionals are face-to-face (n=14; 93.3%) and by as telephone (n=7; 46.7%). Conclusion: Family members and healthcare professionals agree that communication and information transfer are important for the family member to have an experience that generates a positive perception for the family member. Aligning and standardizing the transfer process can be one way to improve it. Or having a referral as part of the care team who can welcome, assist and guide the family member after the patient is transferred to the receiving facility is another solution proposed by the study participants. facility.

Coronaviruses have caused three large outbreaks in the past century. The most recent one, also still ongoing, is represented by the SARS-CoV-2/Covid-19 pandemic. Efforts have been taken to develop efficient vaccines and antivirals and one of the major virus-based targets in drug development is represented by the main protease of these viruses. Main proteases are proteins (cysteine hydrolases) with high level of conservation among different coronaviruses and have an important role in the virus life cycle. Due to the need of developing broad-spectrum antivirals against Coronaviruses, this study aimed to set up a CPE-based assay for testing compounds against the main protease of human coronavirus 229E. An optimized TCID50 protocol was established by using MRC-5 cells, at a density of 1x104 cells/ml with a 3h incubation prior infection with a concentration of 10-1 of HCoV-229E. The cell viability was assessed through MTT assay. Using reference compounds, with previously demonstrated antiviral potency against the main protease of different coronaviruses (GC-376, Nirmatrelvir), the efficiency of the conceived assay was validated (GC-376 EC50 = 1.24 μM; Nirmatrelvir Ec50= 0.72 μM). Compound 19 was proved to also be active against the main protease of HCoV-229E (EC50 = 0.22 μM), and together with previous findings, it was concluded that this compound has a broad-spectrum activity. Newly developed compounds MP17 and MP19 were also demonstrated to be efficient against HCoV-229E. As a future perspective, further investigations of these compounds should take place for the identification of EC50 values.

Time-resolved cryo-EM has already provided ground-breaking discoveries in various fields, including structural biology, biochemistry, and drug development. Compared to traditional structural biology methods where mostly stabilized conformations are reconstructed, the main advantage of time-resolved cryo-EM is its ability to capture dynamic processes in biological samples at near-atomic resolution, which allows for studying biological structures as they change and interact in real-time. In this project, I focused on the expression and purification of the individual proteins of two dynamic molecular complexes – Staphylococcus aureus (S. aureus) DNA gyrase and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication-transcription complex – and attempted to assemble them into their functional forms for cryo-EM imaging.  Both of these complexes are interesting drug targets as they play an essential role in nucleic acid replication. The function of DNA gyrase is to modulate DNA supercoiling, facilitate DNA replication, and resolve intertwined DNA molecules. The replication-transcription complex of SARS-CoV-2 comprises, among other proteins, the RNA-dependent RNA polymerase, which, together with non-structural proteins 7 and 8, is responsible for the replication of the viral genome. There are still many questions about the underlying mechanisms of these key processes, and time-resolved cryo-EM studies will provide valuable information to advance our understanding of them. Here I present expression and purification protocols for S. aureus DNA gyrase subunits A and B and SARS-CoV-2 non-structural proteins 7, 8 and 12. DNA gyrase subunits A and B were expressed in Escherichia coli (E. coli) and purified in several steps, including affinity chromatography (His-Trap), ion exchange chromatography (IEX) and size exclusion chromatography (SEC). Despite many challenges with gyrase A precipitation, I obtained enough of both subunits for the intended cryo-EM. Different strategies to assemble them into a functional tetramer were tested but did not result in the expected outcome. The gained knowledge about the behaviour of the subunits in solution will serve as a basis for further optimization of the protocols before the assembly of the complex can be attempted again. Non-structural proteins 7 and 8 were expressed in E. coli as a polyprotein and successfully purified using His-Trap and SEC. I obtained a great amount of the polyprotein and established a protocol for its cleavage. Nsp12 was expressed using the baculovirus-insect cell expression system. The immunofluorescence assay data showed that the tested lipofection protocol works, and nsp12 is being produced in sufficient quantities. This result provides a solid base for further experiments to establish a purification method and assemble the nsp12-nsp7-nsp8 complex for cryo-EM imaging.