Made available in DSpace on 2015-05-14T12:14:04Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 639748 bytes, checksum: 09ac6e93733c265a01578d25967f780c (MD5) Previous issue date: 2009-10-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In this thesis, we develop some phenomenological aspects of a model based on the gauge symmetry SU(3)CNSU(3)LNU(1)N (311νR), that include righthanded neurinos in its matter content. We establish all the necessary structure for the study of the phenomenological aspects of the model. First, we obtain bounds on the angle that mix the gauge bosons Z and Z′, taking into account a requirement of the model, namely, that the number of fermionic families is exactly three. Also we implement the mass for both species of neutrinos (left-hand and right-handed) via type II seesaw mechanism, obtained adding to the model a sextet of scalars which will be responsible by the violation of the lepton number. The main consequence is the rising of a sterile neutrino with mass in the KeV range, satisfying all the cosmological and astrophysical constraints. This neutrino will a viable candidate for warm dark matter in the universe. / Nesta tese, desenvolvemos alguns aspectos relacionados `a fenomenologia de um modelo com simetria de gauge SU(3)CNSU(3)LNU(1)N (331νR), que possui neutrinos de m ao direita no seu conte´udo de mat´eria. Estabelecemos toda a estrutura necess´aria para o estudo dos aspectos fenomenol´ogicos do modelo. Primeiro, vamos obter v´ınculos no angulo que mistura os b´osons de gauge Z e Z′, levando em conta uma exig encia imposta pelo modelo, ou seja, que o n´umero de fam´ılias fermi onicas ´e exatamente tr es. Tamb´em implementamos termos de massa para ambas as esp´ecies de neutrinos (m ao esquerda e m ao dieita) via mecanismo seesaw tipo II, obtido adicionado ao modelo um sexteto de escalares, que ser´a respons ´avel pela viola¸c ao do n´umero lept onico. A principal consequ encia ´e o surgimento de um neutrino est´eril com massa na escala de KeV , satisfazendo todas as restri¸c oes cosmol´ogicas e astrof´ısicas. Esse neutrino ser´a um vi´avel candidato `a mat´eria escura morna do universo.

Diversos países vêm adotando diretrizes que relacionam prazo de validade de esterilidade de materiais críticos utilizados na assistência à saúde com a ocorrência de eventos relacionados. Pesquisas têm validado a manutenção da esterilidade do material durante o transporte e armazenamento por longos intervalos de tempo. O racional teórico já refutava o antigo paradigma de prazo de validade de esterilidade, baseado no tempo relógio/calendário justificado pela eficiência das embalagens com características de barreira microbiana, selagem hermética e a teoria da ausência de geração espontânea dos micro-organismos. No entanto, no Brasil, pode-se afirmar que os Centros de Material e Esterilização ainda praticam o controle de materiais esterilizados, baseado em data arbitrariamente atribuída, sendo esta prática incentivada por recomendações de documentos elaborados por órgãos oficiais normatizadores e fiscalizadores nacionais. Na crença de que realizar uma investigação experimental in vitro, produzindo evidências científicas robustas contribuiria no fortalecimento da quebra do antigo paradigma, propôs-se avaliar a manutenção da esterilidade de materiais armazenados por até 6 meses, após as embalagens diversas sofrerem contaminação intencional em suas superfícies externas. O experimento consistiu em embalar corpos de prova que simulassem instrumental cirúrgico (cilindros de porcelana) em quatro diferentes tipos de invólucros: algodão tecido, papel crepado, tecido nãotecido (SMS) e papel grau-cirúrgico. Todos os pacotes foram previamente autoclavados em um mesmo ciclo de esterilização. Posteriormente, as superfícies externas dos pacotes foram intencionalmente manipuladas com mãos contaminadas com Serratia marcescens (106 U.F.C./mL). Após intervalos predeterminados de armazenamento (0, 7, 14, 28, 90 e 180 dias), uma quantidade determinada de pacotes de cada tipo de embalagem foi aberta e os corpos de prova foram semeados diretamente em meio de cultura caseína-soja. Os pacotes com corpos de prova com tempo zero de armazenamento foram considerados como grupo controle negativo. Com a finalidade de garantir a viabilidade do micro-organismo-teste na superfície externa das embalagens foram realizados semanalmente, até 180 dias, cultivos das amostras de cada uma das embalagens contaminadas com o micro-organismo-teste, constituindo-se o grupo controle positivo. Para cada intervalo de tempo de armazenamento, foram analisados 600 corpos de prova (150 para cada tipo de embalagem). Considerando o intervalo de confiança exato para distribuição binomial, o tamanho de amostra calculado na pesquisa garantiu um intervalo de confiança de 95% com probabilidade de 0 a 0,006 de se encontrar uma amostra contaminada. Como resultado, não foram recuperados micro-organismos-teste Serratia marcescens em nenhum dos intervalos de tempo de armazenamento. Todos os testes realizados no grupo controle positivo apresentaram recuperação do micro-organismo-teste. Com base nos resultados deste estudo, observou-se que pacotes embalados em invólucros com propriedades de barreiras microbianas e selados hermeticamente são capazes de proteger Resumo Giovana Abrahão de Araújo Moriya o conteúdo esterilizado por até 6 meses. Este estudo contribui para a prática em Centros de Material e Esterilização, impedindo o reprocessamento desnecessário dos materiais, ao mesmo tempo, alerta para que os eventos relacionados sejam controlados e que cada material, antes da sua utilização, seja inspecionado quanto à integridade da embalagem e selagem. / Many countries have adopted guidelines that relate sterility validity period of health care critical materials with the occurrence of related events. Research has validated the maintenance of sterility of the material during transportation and storage for long periods of time. The theoretical rationale has already refuted the old paradigm of sterility validity period based on the time clock/calendar (time-related) due to the efficiency of packaging with microbial barrier characteristics, hermetic seal and the theory of absence of spontaneous generation of micro-organisms. However, in Brazil, it can be stated that the Central Supply and Sterilization Departments still practice the control of sterilized materials based on arbitrarily assigned deadlines, this practice is encouraged by recommendation documents drawn up by official national entities of standardizing and supervising. In the belief that performing an experimental investigation in vitro, producing robust scientific evidence, would help in strengthening the breaking of the old paradigm, we proposed to evaluate the maintenance of sterility of materials stored for up to 6 months after the packages suffer intentional contamination of their external surfaces. The experiment consisted of packing the specimens that simulate surgical instrument (porcelain cylinders) in four different types of wrappers: cotton, crepe paper, nonwoven fabric (SMS) and paper-plastic pouches. All packages have previously been autoclaved at the same sterilization cycle. Subsequently, the external surfaces of the packages were intentionally manipulated with hands contaminated with Serratia marcescens (106 C.F.U./mL). After storage at predetermined intervals (0, 7, 14, 28, 90 and 180 days), a specific quantity of packages of each type of packaging has been opened and the samples were seeded directly in soybean-casein culture medium. The packages with samples with zero time of storage were considered as negative controls. In order to ensure the viability of the test micro-organism on the outer surface of the packages, cultivation of samples of each package contaminated with the test microorganism were made weekly up to 180 days, constituting the positive control group. For each interval of time of storage, 600 samples were analyzed (150 for each type of package). Considering the confidence interval for the exact binomial distribution, the sample size calculated in the study ensured a confidence interval of 95% with 0 to 0.006 probability of finding a contaminated sample. As result, there were no recovered test micro-organism Serratia marcescens in any of the time intervals of storage. Based on the results of this study, it was observed that packages wrapped in wrappers with microbial barrier properties and hermetically sealed are capable of protecting the sterile contents up to 6 months. This study contributes to the clinical practice in Central Supply and Sterilization Department, preventing unnecessary reprocessing of the material, while warns that the related events should be monitored and each material, before use, must be inspected for its integrity of the packaging and sealing.

La voie des RLR (RIG-I like Receptors) joue un rôle essentiel dans la détection des virus à ARN, déclenchant une réponse immunitaire antivirale grâce au recrutement de la protéine adaptatrice mitochondriale MAVS (Mitochondrial AntiViral Signaling protein). Nous avons mis en évidence que les souris déficientes pour la protéine MAVS (MAVS KO) présentaient un phénotype proallergénique dans un modèle d'inflammation stérile d'hypersensibilité retardée de contact (HSRC) qui reproduit la dermatite allergique de contact (DAC) chez l'homme. Nous avons caractérisé le système immunitaire des souris MAVS KO en condition d'équilibre et durant la réponse d'HSRC. Nous avons identifié un rôle du microbiote intestinal des souris MAVS KO dans l'exacerbation de réponse d'HSRC et mis en évidence une dysbiose du microbiote bactérien. Nous avons démontré que la dysbiose était responsable du phénotype inflammatoire observé, phénotype transmissible à des souris sauvages par des expériences de cohébergement et de transplantation fécale. Cette dysbiose induit une augmentation de la perméabilité intestinale chez les souris MAVS KO lors de la réponse d'HSRC, aboutissant à une translocation bactérienne dans les organes lymphoïdes et à la modulation des réponses immunitaires à l'origine de l'exacerbation de réponse d'hypersensibilité. La 2ème partie de ma thèse vise à étudier les conséquences de la déficience en MAVS sur le métabolisme glucidique. Nos expériences ont démontré que les souris MAVS KO développaient une surcharge pondérale et une insulino-résistance sous régime riche en lipides et sucrose, dépendants de la dysbiose intestinale. Au niveau cellulaire, une altération des interactions aux points de contact entre la mitochondrie et le réticulum endoplasmique a été observée. Nos résultats permettent d'envisager le développement de nouvelles approches thérapeutiques des pathologies allergiques et métaboliques humaines par la modulation du microbiote intestinal / RIG-I like receptors (RLRs) play a major role in response to cytosolic viral RNAs by initiating an antiviral immune response through the recruitment of the mitochondrial adaptor protein MAVS (Mitochondrial AntiViral Signaling protein). We showed that MAVS-deficient mice developed an exacerbated response in a sterile inflammatory model of Contact Hypersensitivity (CHS), that reproduces the pathophysiology of allergic contact dermatitis (ACD) in human. We characterized the immune system of MAVS KO mice at steady state and during CHS response. We found that MAVS deficiency leads to changes in the gut bacterial composition suggesting an unexpected role of the RLR pathway in the regulation of intestinal homeostasis. We demonstrated that intestinal dysbiosis is responsible for the increased CHS response, and showed that the inflammatory phenotype of MAVS KO mice can be transferred to WT mice by cohousing and fecal transplantation. We demonstrated that the dysbiotic gut microbiota exerts its effect due to an increased intestinal permeability during DTH sensitization. The ensuing bacterial translocation within lymphoid organs enhances characteristic cytokines production that increases CHS response. The 2nd part of my thesis aimed to study the consequences of MAVS deficiency on glucose metabolism. Our experiments showed that MAVS KO mice exhibit disorders of glucose homeostasis during high fat diet (HFD) associated with the development of overweight and insulin resistance. We also observed alterations of MAM (Mitochondria-associated endoplasmic reticulum membranes), contact poins between mitochondria and endoplasmic reticulum. Recent preliminary data suggested that the metabolic disorders associated with MAVS deficiency are due to intestinal dysbiosis. Our results highlight a new role for the RLR pathway and allow to consider the development of new therapeutic approaches to human allergic and metabolic diseases by modulation of the intestinal microbiota

Introduktion Hög luftfuktighet har i flera år orsakat problem i sterilförråd på svenska sjukhus. Sterila förpackningar ska enligt standard förvaras i en temperatur på 22±3 ˚C och i en luftfuktighet på 30-70 %. För att relativt enkelt och kostnadseffektivt få bukt med fuktighetsproblemet installeras avfuktare. Inga studier finns på hur avfuktare fungerar i sterila miljöer. Elimineras risken för fuktiga emballage utan tillväxt av mikroorganismer i förråd med sterilt material. Syfte Syftet med studien är att undersöka om den lokala avfuktaren Dantherm kan bidra till en kontrollerad miljö genom att antal bakteriebärande partiklar, dvs. colony forming units (cfu) i protesförråd och sterilförråd håller sig inom godkända nivåer relaterat till rekommendationerna i den tekniska standarden SIS TR 57:2020, dvs. 100 cfu/m3 när avfuktaren är installerad och aktiverad. Metod Studien är en kvantitativ pilotstudie. Aktiv och passiv luftprovtagning utfördes i två förråd med två olika sorters Danthermavfuktare samt i två andra förråd, dvs. ett förråd med avfuktare av märket Wood’s och ett förråd helt utan avfuktning. Åtta mättillfällen gjordes per förråd mellan slutet av juni till mitten av oktober år 2020. Resultat Resultatet visar att de allra flesta värdena låg inom referensvärden enligt standard. Slutsats Dantherm avfuktaren verkar bidra till en kontrollerad miljö i förråd med sterilt material. De gånger avfuktaren var aktiv kontaminerade den inte miljön med mikroorganismer. Således kommer den att installeras i fler förråd med sterilt material på Hallands sjukhus och utvärderas kontinuerligt nästkommande år. / Introduction High humidity has been a problem for a long time in sterile storage rooms in Swedish hospitals. According to standards temperature in sterile storage rooms should be within 22±3˚C and the relative humidity 30-70 %. In order to achieve these conditions in a relatively easy and cost effective way, local dehumidifiers have been installed. No previous studies on eliminating the risk of moist packaging without microbial growth in sterile storage rooms have been carried out. Aim The aim of the study is to evaluate whether the dehumidifier Dantherm could contribute to a controlled environment by keeping colony forming units (cfu) in the storage rooms called protesförråd (prostheses storage room) and sterilförråd (sterile storage room) within recommendations according to the standard technical report SIS TR 57:2020 written by Swedish institute of standards, i.e. 100 cfu/m3 when the dehumidifiers are installed and running. Method This study is a quantitative pilot study. Active and passive air sampling were made in two sterile storage rooms with two different kinds of Dantherm dehumidifiers. Two other sterile storage rooms were sampled of which one had a Wood’s dehumidifier installed and the other one lacked totally a dehumidifier. Eight measurements per storage room were made from the end of June to mid-October in the year 2020. Results The results show that almost all rates were within recommended limits. Conclusion The Dantherm dehumidifier seems to contribute to a controlled environment in sterile storage rooms as it did not introduce additional microbiological contamination. Consequently, it will be installed in several more sterile storage rooms at Halland’s hospitals and will be continuously evaluated next year.

Preterm labor with intact membranes (PTL) is responsible for approximately 40% of all preterm deliveries. PTL is frequently complicated by intra-amniotic inflammation (IAI), characterized by the elevation of inflammatory mediators in the amniotic fluid. Based on the presence or absence of microbial invasion of the amniotic cavity (MIAC), two different clinical phenotypes of IAI are distinguished: i) intra-amniotic infection, when microorganisms are present in the amniotic fluid, and ii) sterile IAI, when there are no microorganisms in the amniotic fluid. The clinical severity of both phenotypes of IAI is underlined by their association with adverse neonatal outcomes. In addition to the presence or absence of MIAC, there are also differences between the phenotypes of IAI in terms of their intra-amniotic inflammatory status characteristics. The clinical part of this thesis has addressed these differences in women with PTL. The first specific aim of this clinical study was to determine the concentration of interleukin (IL)-6 in the cervical fluid of women with PTL complicated by intra-amniotic infection and sterile IAI. The second specific aim was to determine the concentration of IgGFc-binding protein (FcgammaBP) in the amniotic and cervical fluids of women with PTL complicated by intra-amniotic...

Sterilcentralen som finns på nya Karolinska Universitetssjukhuset är inte modern. Den är dessutom inte tillfredsställande ur ett arbetsmiljömässigt perspektiv.  Det finns redan ett antal beprövade automationsmetoder som är implementerade på olika sjukhus, men inte på NKS. Det finns ett antal olika processer som ett material måste genomgå för att det ska bli sterilt. De flesta sköts manuellt. Kan automation förverkligas för att minska mängden manuellt arbete samt förbättra arbetsmiljön för avdelningens personal? Ett frågeformulär användes för att ta reda på hur personalen som arbetar på avdelningen uppfattar arbetet som utförs. Formuläret var också till för att ta reda på hur de tror att arbetet och arbetsmiljön kan förbättras genom automation. Fältstudier samt besök på andra sjukhus gjordes för att undersöka hur arbetet på sterilcentralen går till i praktiken. / The central sterile department that is located at the new Karolinska Hospital is not up to date. It is not satisfying from a work environmental perspective. There are however a number of proven methods of automation that are implemented at different hospitals but not at NKS. There are a number of different processes that have to be executed on an instrument to be able to classify it as sterile. Most of the work is done manually. Could automation be implemented to reduce the number of work done manually and to improve the work environment for the employees of the department? A questionnaire was used to figure out how the staff that works at the department perceives the work that is being done. The questionnaire was also used to figure out the staff's point of view on how the work processes and work environment can be improved due to automation. Field studies and visiting other hospitals were executed to study how the work at the central sterile department is done in reality.