Toll-like receptors (TLRs) are a major group of pattern recognition receptors expressed on the surface of immune cells that recognize molecular patterns associated with all classes of pathogenic microorganisms. TLR4 recognizes the lipopolysaccharide component of Gram-negative bacterial cell walls and is the only TLR known to induce signaling through both the MyD88 and TRIF pathways. Basigin, a ubiquitous cell adhesion molecule, is a member of the immunoglobulin superfamily that has the ability to influence cell signaling mediated by the MyD88 and TRIF pathways, the same signaling pathways induced by the TLR4 receptor protein. Analysis of the Basigin protein sequence indicates the presence of a hydrophilic glutamate residue within the hydrophobic transmembrane domain, but no consensus binding sites for MyD88 or TRIF. The purpose of this study was to determine if Basigin uses TLR4 for signal transduction. It is hypothesized that Basigin interacts with TLR4 and that the glutamate residue plays a role in the interaction. Enzyme-linked immunosorbent binding assays were performed using endogenous TLR4 and recombinant Basigin proteins. These analyses demonstrated that binding of Basigin to TLR4 was significantly greater than that of the control protein and that the glutamate residue in the Basigin transmembrane domain does play a role in the interaction between Basigin and TLR4 as well as many hydrophobic residues in the Basigin transmembrane domain. The data suggest that Basigin interacts with TLR4 to influence signaling cascades using MyD88 and TRIF.

BACKGROUND: The needle exchange programme (NEP) started in Sweden in 1986 in Lund and shortly after in Malmo. The first NEP in Stockholm opened in spring 2013. The NEP is a service aimed at intravenous drug users (IDU) from 18 years old, with a goal of preventing the blood borne diseases, such as HIV, Hepatitis B (HBV), and Hepatitis C (HCV). With the on going HIV and Hepatitis epidemics, numerous countries around the world have adopted control strategies, such as the NEP to halt the spread of HIV, HBV, and HCV. The objective of this study was to examine if the needle exchange programme has decreased the incidence of HIV, HBV, and HCV in Sweden over a six-year period.  METHODS: Data for incidence and prevalence was extracted from the yearly reports of the Stockholm’s needle exchange programme from 2013 to 2018 and the yearly reports of the public health agency in Sweden from 2013 to 2018. The data was collected for Stockholm, and compared to Västra Götaland, and the whole of Sweden. RESULTS: The incidence of HIV was zero in 2013 and 2015 in the NEP. The incidence of HBV decreased to zero in 2013 in the NEP. There is an increased incidence of HCV in the NEP. CONCLUSION: The NEP has a protective effect through its combination of needle exchange, opiate substitute therapy, counselling, and vaccinations in reducing and stabilising incidences of the infections, in some instances to zero, as well as providing surveillance and treating infections.

Ces dernières années, la puissance croissante des ordinateurs a permis à la fois de rassembler une quantité sans précédent de données décrivant la société moderne et d'envisager des outils numériques capables de s'attaquer à l'analyse et la modélisation les processus dynamiques qui se déroulent dans cette réalité complexe. Dans cette perspective, l'approche quantitative de la physique est un des catalyseurs de la croissance de nouveaux domaines interdisciplinaires visant à la compréhension des systèmes complexes techno-sociaux. Dans cette thèse, nous présentons dans cette thèse un cadre théorique et numérique pour simuler des épidémies de maladies infectieuses émergentes dans des contextes réalistes. Dans ce but, nous utilisons le rôle crucial de la mobilité des agents dans la diffusion des maladies infectieuses et nous nous appuyons sur l'étude des réseaux complexes pour gérer les ensembles de données à grande échelle décrivant les interconnexions de la population mondiale. En particulier, nous abordons deux différents problèmes de santé publique. Tout d'abord, nous considérons la propagation d’une épidémie au niveau mondial, et présentons un modèle de mobilité (GLEAM) conçu pour simuler la propagation d'une maladie de type grippal à l'échelle globale, en intégrant des données réelles de mobilité dans le monde entier. La dernière pandémie de grippe H1N1 2009 a démontré la nécessité de modèles mathématiques pour fournir des prévisions épidémiques et évaluer l'efficacité des politiques d'interventions. Dans cette perspective, nous présentons les résultats obtenus en temps réel pendant le déroulement de l'épidémie, ainsi qu'une analyse a posteriori portant sur les stratégies de lutte et sur la validation du modèle. Le deuxième problème que nous abordons est lié à la propagation de l'épidémie sur des systèmes en réseau dépendant du temps. En particulier, nous analysons des données décrivant les mouvements du bétail en Italie afin de caractériser les corrélations temporelles et les propriétés statistiques qui régissent ce système. Nous étudions ensuite la propagation d'une maladie infectieuse, en vue de caractériser la vulnérabilité du système et de concevoir des stratégies de contrôle. Ce travail est une approche interdisciplinaire qui combine les techniques de la physique statistique et de l'analyse des systèmes complexes dans le contexte de la mobilité des agents et de l'épidémiologie numérique. / In recent years, the increasing availability of computer power has enabled both to gather an unprecedented amount of data depicting the global interconnections of the modern society and to envision computational tools able to tackle the analysis and the modeling of dynamical processes unfolding on such a complex reality. In this perspective, the quantitative approach of Physics is catalyzing the growth of new interdisciplinary fields aimed at the understanding of complex techno-socio-ecological systems. By recognizing the crucial role of host mobility in the dissemination of infectious diseases and by leveraging on a network science approach to handle the large scale datasets describing the global interconnectivity, in this thesis we present a theoretical and computational framework to simulate epidemics of emerging infectious diseases in real settings. In particular we will tackle two different public health related issues. First, we present a Global Epidemic and Mobility model (GLEaM) that is designed to simulate the spreading of an influenza-like illness at the global scale integrating real world-wide mobility data. The 2009 H1N1 pandemic demonstrated the need of mathematical models to provide epidemic forecasts and to assess the effectiveness of different intervention policies. In this perspective we present the results achieved in real time during the unfolding of the epidemic and a posteriori analysis on travel related mitigation strategies and model validation. The second problem that we address is related to the epidemic spreading on evolving networked systems. In particular we analyze a detailed dataset of livestock movements in order to characterize the temporal correlations and the statistical properties governing the system. We then study an infectious disease spreading, in order to characterize the vulnerability of the system and to design novel control strategies. This work is an interdisciplinary approach that merges statistical physics techniques, complex and multiscale system analysis in the context of hosts mobility and computational epidemiology.

As alterações neurocognitivas associadas ao HIV-1 (HAND) são frequentes em adultos infectados pelo HIV-1 via transmissão sexual. Existe pouca informação sobre HAND em adultos infectados pelo HIV-1 via transmissão vertical. Este estudo teve como objetivos identificar a prevalência das HAND em adultos infectados por transmissão vertical assim como identificar a prevalência de depressão nessa população. Pacientes e métodos: trata-se de um estudo de delineamento transversal, realizado entre janeiro 2016 e maio de 2017, no Serviço de Extensão ao Atendimento de Pacientes HIV/aids (SEAP) da Divisão de Moléstias Infecciosas e Parasitárias do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. O SEAP é um serviço exclusivamente ambulatorial, localizado na cidade de São Paulo. Os critérios de inclusão foram: (i) pacientes com diagnóstico de infecção pelo HIV-1 por transmissão vertical; (ii) idade igual ou superior a 18 anos; (iii) escolaridade mínima de 4 anos; e (iv) consentimento para participar do estudo. Os critérios de exclusão foram: (i) diagnóstico concomitante de doenças neurológicas oportunistas ou condições neurológicas, previamente documentadas; (ii) uso de substâncias psicoativas; (iii) incapacidade física para aplicação dos testes, (iv) recusa da assinatura do Termo de Consentimento Livre e Esclarecido. Foram utilizados como instrumentos de pesquisa: questionário sociodemográfico, escala de ansiedade e depressão hospitalar, escala de atividades de vida diária de Lawton e bateria neuropsicológica formal. Para análise estatística foram calculadas frequência, média e desvio padrão, assim como testes qui-quadrado, anova e análise posthoc. Valores de p < 0.05 foram considerados estatisticamente significativos. Foi utilizado o programa SPSS 21.0. Resultados: foram avaliados 28 participantes: 15 (53.6%) foram do sexo feminino e a idade média e o desvio padrão (DP) foi de 22 (6.7) anos. Foi identificado HAND em 23 (82,1%) pacientes: 12 (42.9%) tiveram alteração neurocognitiva assintomática (ANI), 6 (21,4%) tiveram comprometimento neurocognitivo leve (MND) e 5 (17.9%) tiveram demência associada ao HIV-1 (HAD). A atenção, velocidade de processamento e velocidade motora foram as funções cognitivas mais comprometidas. 3 (10.7%) pacientes apresentaram depressão; 3 (60%) dos 5 pacientes com HAD apresentaram depressão. Conclusões: neste estudo encontramos elevada prevalência de HAND em adultos infectados pelo HIV-1 via transmissão vertical, chamando atenção também a elevada proporção de pacientes com HAD. Por outro lado, identificamos baixa prevalência de depressão na população total do estudo, mas a prevalência de depressão foi elevada dentre os pacientes com HAD / Neurocognitive disorders associated with HIV-1 (HAND) are common in adults sexually infected with HIV-1. There is little information about HAND in adults vertically infected with HIV-1. This study aimed to identify the prevalence of HAND in adults vertically infected with HIV-1 as well as to identify the prevalence of depression in this population. Patients and methods: This is a cross-sectional study, conducted between January 2016 and May 2017, at the Extension Service for HIV/aids Patients (SEAP) of the Division of Infectious and Parasitic Diseases of the Hospital das Clínicas of University of São Paulo Medical School. SEAP is an exclusively outpatient service, located in the city of São Paulo. Inclusion criteria were: (i) patients diagnosed with HIV-1 infected by vertical transmission; (ii) age equal to or more than 18 years; (iii) minimum schooling of 4 years; and (iv) consent to participate in the study. Exclusion criteria were: (i) concomitant diagnosis of opportunistic neurological diseases or neurological conditions, previously documented; (ii) use of psychoactive substances; (iii) physical incapacity to apply the tests, (iv) refusal to sign the Free and Informed Consent Form. The following research assessment tools were used: sociodemographic questionnaire, hospital anxiety and depression scale, Lawton daily life activity scale and formal neuropsychological battery. For statistical analysis, we calculated frequency, mean and standard deviation, as well as chi-square, anova and post-hoc analysis. Values of p < 0.05 were considered statistically significant. The SPSS 21.0 program was used. Results: 28 participants were evaluated: 15 (53.6%) were female and the mean age and standard deviation (SD) were 22 (6.7) years. HAND was identified in 23 (82.1%) patients: 12 (42.9%) had asymptomatic neurocognitive impairment (ANI), 6 (21.4%) had mild neurocognitive impairment and 5 (17.9%) had dementia associated with HIV-1 (HAD). Attention, processing speed and motor speed were the most compromised cognitive functions. 3 (10.7%) patients presented depression; 3 (60%) of the 5 patients with HAD had depression. Conclusions: in this study we found a high prevalence of HAND in adults vertically infected, also calling attention to the high proportion of patients with HAD. On the other hand, we identified a low prevalence of depression in the total study population, but the prevalence of depression was high among patients with HAD

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1–324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

INTRODUÇÃO: Tem havido um crescente interesse em desenvolver programas para oferecer cuidados em casa para as condições que têm sido tradicionalmente tratadas nos hospitais, impulsionado por uma série de fatores, incluindo considerações de custo, a preferência do paciente e o aumento do risco de infecções adquiridas no hospital. As infecções são uma importante causa de internação e os antimicrobianos estão entre os fármacos mais comumente prescritos, o uso inadequado e disseminado está associado ao aparecimento de patógenos resistentes. Na oncologia os pacientes constituem um grupo sob especial risco de infecções. Estudos específicos sobre conversão de antimicrobianos em oncologia não são facilmente encontrados na literatura. OBJETIVO: Avaliar a eficácia do protocolo de um programa de terapia sequencial de antimicrobiano em hospital referência em oncologia. MÉTODO: Estudo retrospectivo de avaliação de intervenção, realizado em internação de um instituto de alta complexidade em oncologia, no período de maio de 2011 a maio de 2012, com etapa observacional pré-intervenção, e etapa de intervenção com aplicação do protocolo de terapia sequencial, onde ocorre a substituição do mesmo antimicrobiano de via intravenosa para a via oral. RESULTADOS: Foram incluídos 889 pacientes, 357 no período pré-intervenção e 532 no período de intervenção. Não houve diferença estatisticamente significativa na proporção de trocas entre os grupos pré-intervenção e intervenção, 33,61% e 37,59% respectivamente (OR 1,19, IC95% 0,90-1,58, p 0,23). Porém houve diferença para uso de levofloxacino, com maior chance de troca no grupo de intervenção (OR 2,94, IC95% 1,58-5,58, p 0,008). A neoplasia de mama como diagnóstico oncológico também foi associada a maior chance de troca (OR 2,10 IC95% 1,04-4,23, p 0,04). CONCLUSÃO: A implementação de protocolo de um programa de terapia sequencial em pacientes oncológicos em regime de internação não demonstrou impacto na troca de antimicrobiano IV para VO. Entretanto, resultou em maior chance de troca quando aplicada nos casos do uso de levofloxacino e naqueles cujo diagnóstico oncológico era neoplasia de mama / INTRODUCTION: There has been a growing interest in developing programs to provide home care for some conditions that have traditionally been treated in hospitals due to a number of factors, including cost considerations, the patient\'s preferences and the increased risk of infections acquired in the hospital. Infections are a major cause of hospitalization and the antimicrobials are among the most commonly prescribed drugs, their improper and widespread use is associated with the emergence of resistant pathogens. Oncology patients constitute a group at particular risk of infections. Specific studies on conversion of antimicrobial agents in Oncology are not easily found in the literature. OBJECTIVE: to evaluate the effectiveness of a program of sequential antimicrobial therapy in an Oncology hospital. METHOD: Retrospective study of intervention evaluation, conducted in hospitalized patients in an Oncology Institute from May 2011 to May 2012, with an observational pre-intervention step as well as a step of intervention with application of sequential therapy protocol, where the same antimicrobial is administered orally instead of via IV. RESULTS: Eight hundred and eighty-nine patients were included, 357 in the pre-intervention phase and 532 in the intervention phase. There was no statistically significant difference in the proportion of changing between the pre-intervention and intervention groups, 33.61% and 37.59% respectively (OR 1.19, IC95% 0.90-1.58, p 0.23). But there was difference for the use of levofloxacin, with greater chance of switching in the intervention group (OR 2.94, IC95% 1.58-5.58, p 0.008). The breast cancer diagnosis was also associated with greater chance of switching (OR 2.10 IC95% 1.04-4.23, p 0.04). CONCLUSION: The implementation of a protocol of a sequential therapy program in oncology patients in inpatient regime showed no impact on antimicrobial switch from IV to VO. However, it resulted in higher chance of switch when applied in cases of use of levofloxacin and in those whose cancer diagnosis was breast neoplasm

Introdução: O Protocol Aids Clinical Trial Group (PACTG 076), publicado em 1994, demonstrou que a utilização da zidovudina (ZDV) reduzia a taxa de transmissão materno-infantil do HIV (TMI HIV) de 25% para 8,3%. Atualmente a terapia antirretroviral (TARV) combinada associada a uma série de medidas pode reduzir a taxa de TMI HIV para menos de 2%. Embora o Ministério da Saúde preconize a adoção destas medidas, a TMI HIV ainda permanece acima dos níveis desejados, principalmente em nosso meio. De acordo com levantamento da Vigilância Epidemiológica do Município de Porto Alegre, no ano de 2012 a taxa TMI HIV foi de 2,9%. Objetivo: Avaliar os fatores que interferem na TMI HIV em um Hospital Universitário do Município de Porto Alegre/RS. Método: Trata-se de um estudo de coorte histórico, tendo como amostra 292 bebês nascidos de mulheres portadoras do HIV, cujos nascimentos ocorreram no Centro Obstétrico de um Hospital Universitário do Município de Porto Alegre/RS, entre 1º de janeiro de 2010 a 31 de dezembro de 2014. Resultados: Dos 292 bebês, cujas mães eram portadoras do HIV, 3,8% (n=11) foram contaminados. Destes 90,9% (n=10) nasceram por cesariana; 90,9% (n=10) tinham d37 semanas; 54,6% (n=6) receberam ZDV xarope isoladamente e 45,4% (n=5) receberam ZDV + nevirapina (NVP). Quatro gestantes cujos bebês foram contaminados apresentaram sífilis na gestação (36,4%). A má adesão a TARV (p<0,003), a carga viral d1.000 cópias/mL ou ignorada no 3º trimestre (p<0,001) e o CD4 <500 células/mm3 (p<0,046) no terceiro trimestre foram significativamente associados a maior TMI HIV. Conclusão: Os fatores associados significativamente a TMI HIV foram à má adesão a TARV, a presença de sífilis na gestação, a carga viral d1000 cópias e o CD4 <500 células/mm³ no terceiro trimestre. / Introduction: Protocol Aids Clinical Trial Group (PACTG 076), published in 1994, demonstrated that the use of zidovudine (ZDV) had reduced the rate of mother-tochild transmission (MTCT) of HIV from 25% to 8.3%. Currently, a combined antiretroviral therapy (HAART) associated with a number of measures can reduce the rate of MTCT to less than 2%. Although the Ministry of Health recommends the adoption of these measures, the MTCT still remains above desired levels, especially in our center. According to a survey of Epidemiological Surveillance of Porto Alegre, in 2012 the rate of MTCT was 2.9%. Objective: To evaluate the factors that interfere with MTCT from HIV-positive women who gave birth in a University Hospital of Porto Alegre/RS. Method: A historical cohort study, with a sample 292 babies from HIV infected mother whose delivery occurred at Obstetric Center of the University Hospital of Porto Alegre/RS, at period of January 2010 till December 2014. Results: Of 292 babies of women HIV positive, 3.8% (n=11) were infected. Of those 90.9% (n=10) was born by cesarean section; 90.9% (n=10) had d37 weeks; 54.6% (n=6) received only ZDV syrup and 45.4% (n=5) received ZDV+nevirapine (NVP). Four pregnant women whose babies were infected, mother had syphilis during pregnancy (36.4%). Poor adherence to HAART (p<0.003), viral load d1000 copies/mL or ignored in the third trimester (p<0.001) and CD4 <500 cells/mm3 (p<0.046) in the third trimester were significantly associated with higher MTCT. Conclusion: We conclude that the presence of syphilis in pregnancy, viral load d1000 copies/mL or ignored in the third trimester, the CD4 <500 cells/mm³ in the third trimester, poor adherence to HAART were significant factors for MTCT.

INTRODUÇÃO: Tem havido um crescente interesse em desenvolver programas para oferecer cuidados em casa para as condições que têm sido tradicionalmente tratadas nos hospitais, impulsionado por uma série de fatores, incluindo considerações de custo, a preferência do paciente e o aumento do risco de infecções adquiridas no hospital. As infecções são uma importante causa de internação e os antimicrobianos estão entre os fármacos mais comumente prescritos, o uso inadequado e disseminado está associado ao aparecimento de patógenos resistentes. Na oncologia os pacientes constituem um grupo sob especial risco de infecções. Estudos específicos sobre conversão de antimicrobianos em oncologia não são facilmente encontrados na literatura. OBJETIVO: Avaliar a eficácia do protocolo de um programa de terapia sequencial de antimicrobiano em hospital referência em oncologia. MÉTODO: Estudo retrospectivo de avaliação de intervenção, realizado em internação de um instituto de alta complexidade em oncologia, no período de maio de 2011 a maio de 2012, com etapa observacional pré-intervenção, e etapa de intervenção com aplicação do protocolo de terapia sequencial, onde ocorre a substituição do mesmo antimicrobiano de via intravenosa para a via oral. RESULTADOS: Foram incluídos 889 pacientes, 357 no período pré-intervenção e 532 no período de intervenção. Não houve diferença estatisticamente significativa na proporção de trocas entre os grupos pré-intervenção e intervenção, 33,61% e 37,59% respectivamente (OR 1,19, IC95% 0,90-1,58, p 0,23). Porém houve diferença para uso de levofloxacino, com maior chance de troca no grupo de intervenção (OR 2,94, IC95% 1,58-5,58, p 0,008). A neoplasia de mama como diagnóstico oncológico também foi associada a maior chance de troca (OR 2,10 IC95% 1,04-4,23, p 0,04). CONCLUSÃO: A implementação de protocolo de um programa de terapia sequencial em pacientes oncológicos em regime de internação não demonstrou impacto na troca de antimicrobiano IV para VO. Entretanto, resultou em maior chance de troca quando aplicada nos casos do uso de levofloxacino e naqueles cujo diagnóstico oncológico era neoplasia de mama / INTRODUCTION: There has been a growing interest in developing programs to provide home care for some conditions that have traditionally been treated in hospitals due to a number of factors, including cost considerations, the patient\'s preferences and the increased risk of infections acquired in the hospital. Infections are a major cause of hospitalization and the antimicrobials are among the most commonly prescribed drugs, their improper and widespread use is associated with the emergence of resistant pathogens. Oncology patients constitute a group at particular risk of infections. Specific studies on conversion of antimicrobial agents in Oncology are not easily found in the literature. OBJECTIVE: to evaluate the effectiveness of a program of sequential antimicrobial therapy in an Oncology hospital. METHOD: Retrospective study of intervention evaluation, conducted in hospitalized patients in an Oncology Institute from May 2011 to May 2012, with an observational pre-intervention step as well as a step of intervention with application of sequential therapy protocol, where the same antimicrobial is administered orally instead of via IV. RESULTS: Eight hundred and eighty-nine patients were included, 357 in the pre-intervention phase and 532 in the intervention phase. There was no statistically significant difference in the proportion of changing between the pre-intervention and intervention groups, 33.61% and 37.59% respectively (OR 1.19, IC95% 0.90-1.58, p 0.23). But there was difference for the use of levofloxacin, with greater chance of switching in the intervention group (OR 2.94, IC95% 1.58-5.58, p 0.008). The breast cancer diagnosis was also associated with greater chance of switching (OR 2.10 IC95% 1.04-4.23, p 0.04). CONCLUSION: The implementation of a protocol of a sequential therapy program in oncology patients in inpatient regime showed no impact on antimicrobial switch from IV to VO. However, it resulted in higher chance of switch when applied in cases of use of levofloxacin and in those whose cancer diagnosis was breast neoplasm

Human C-reactive protein (CRP) is the prototypic acute phase protein whose serum concentration increases rapidly during inflammation. CRP is also associated with atherosclerosis; it is deposited at lesion sites where it may interact with modified lipoproteins. There are 2 major questions regarding CRP: 1. How is the serum concentration of CRP regulated? 2. What are the functions of CRP in atherosclerosis? Our first aim was to determine the role of the constitutively expressed transcription factor Oct-1 in regulating CRP gene expression. We found that Oct-1 overexpression inhibited (IL-6+IL-1β)- induced CRP gene expression; maximal inhibition required the binding of Oct-1 to an octamer motif at (-59 to -66) on the CRP promoter. Oct-1 overexpression inhibited both (IL-6+IL-1β)- induced and C/EBPβ-induced CRP gene expression even when the Oct-1 site was deleted. These findings suggest that Oct-1 is a repressor of CRP gene expression that acts via binding to its cognate site on the CRP promoter as well as through indirect interactions with other promoterbound transcription factors. Our second aim was to investigate the interaction of CRP with oxidized low density lipoprotein (ox-LDL). Acidic pH, a hallmark of atherosclerotic lesions, reversibly alters CRP structure and exposes a hidden binding site that enables CRP to bind ox-LDL. Using site-directed mutagenesis we constructed a CRP mutant (E42Q) that showed significant binding to ox-LDL at physiological pH. E42Q CRP required a less acidic pH for maximal binding and bound ox-LDL more efficiently than wild type CRP at any pH. We then examined if reactive oxygen species also induced CRP – ox-LDL interaction. H2O2-treated CRP bound ox-LDL at physiological pH. Like acidic pH, H2O2-treatment induced only a local structural change exposing the ox-LDL binding site. E42Q and H2O2-modified CRP are tools to study the function of CRP in animal models of atherosclerosis, which may not have an inflammatory environment sufficient to modify CRP and induce binding to atherogenic ox-LDL. We conclude that Oct-1 is one of the critical regulators of CRP gene expression, and that CRP can be modified in vitro to convert it into an atherogenic LDL-binding molecule.

Historically, 18th century anecdotal accounts of the decimation of several tribes of U.S. of the Native American population by trading of infected textile blankets alludes to the role of retail in the transmission of infectious disease. This study explores implications of the modern day retail organization practice of reselling returned clothing textiles from a public health infectious disease perspective. A qualitative multi-case study, utilized responses from 20 open-ended, unstructured interviews of retail employees assigned to the returns process. Additionally, several informal observations of select U.S.based, top-ranked clothing retail organizations, identified by the National Retail Federation were completed. Select federal, state, and local public health regulations regarding returned clothing textiles were then examined in an attempt to identify potential public health risks. Under a general systems conceptual framework, the points of interaction between the complex adaptive systems seen in retailer and the public health organizations were examined for infectious disease and infestation implications. Using MAXQDA software to perform the analyses, it was found that current retail practices and policy present unacknowledged infectious disease or infestation transmission risks. The risk applies to all, but is particularly relevant to immuno-compromised individuals. Though the risk in accepting and returning clothing to the sales cycle is an industry wide practice, it can be mitigated. Suggested mitigation takes the form of health training, and introduction of disinfection sanitizing tools such as UVC light exposures, into the returns-resale process.The findings point to an opportunity for social change for consumers, retail workers, and the community through update of public health and retail practices.