948 research outputs found

    Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity

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    Neutrophils play an important role in the outcome of leishmaniasis, contributing either to exacerbating or controlling the progression of infection, a dual effect whose underlying mechanisms are not clear. We recently reported that CD4+ and CD8+ T cells, and dendritic cells of Leishmania amazonensis-infected mice present high expression of PD-1 and PD-L1, respectively. Given that the PD-1/PD-L1 interaction may promote cellular dysfunction, and that neutrophils could interact with T cells during infection, we investigated here the levels of PD-L1 in neutrophils exposed to Leishmania parasites. We found that both, promastigotes and amastigotes of L. amazonensis induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites in vitro. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of L. amazonensis-infected mice, assessed through cell cytometry and intravital microscopy. Moreover, expression of PD-L1 progressively increased in neutrophils from ear lesions as the disease evolved to the chronic phase. Co-culture of infected neutrophils with in vitro activated CD8+ T cells inhibits IFN-γ production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that in vitro infection of human neutrophils by L braziliensis induced PD-L1+ expression and also PD-L1+ neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the Leishmania parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response

    Higher IL-10 levels are associated with less effective clearance of Plasmodium falciparum parasites

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    The implications of high levels of the immune regulatory cytokine IL-10 in Plasmodium falciparum malaria are unclear. IL-10 may down-regulate pro-inflammatory responses and also exacerbate disease by inhibiting anti-parasitic immune functions. To study possible inhibiting effects on parasite clearance, IL-10 plasma levels were determined in 104 Tanzanian children, 1 to 4 years old, with acute uncomplicated P. falciparum malaria, and analysed for association with parasite densities during 3 days of anti-malarial treatment. Higher baseline IL-10 plasma levels were associated with statistically significantly higher parasite densities after 24, 48 and 72 h of treatment. These associations could not be explained by differences in initial parasitaemia, temperature, age, sex or type of treatment. Induction of high IL-10 production might be a direct or indirect mechanism whereby the parasite evades the immune response

    Impact of COVID-19 on 1-year survival outcomes in hepatocellular carcinoma: a multicenter cohort study

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    INTRODUCTION: The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients' access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes. METHODS: A prospective cohort study was conducted from 1 March 2020 until 30 June 2020, correlating to the first wave of the COVID-19 pandemic. Patients were enrolled from tertiary hospitals in the UK and Germany with dedicated HCC management services. All patients with current or past HCC who were discussed at a multidisciplinary meeting (MDM) were identified. Any delay to treatment (DTT) and the effect on survival at one year were reported. RESULTS: The median time to receipt of therapy following MDM discussion was 49 days. Patients with Barcelona Clinic Liver Cancer (BCLC) stages-A/B disease were more likely to experience DTT. Significant delays across all treatments for HCC were observed, but delay was most marked for those undergoing curative therapies. Even though severe delays were observed in curative HCC treatments, this did not translate into reduced survival in patients. CONCLUSION: Interruption of routine healthcare services because of the COVID-19 pandemic caused severe delays in HCC treatment. However, DTT did not translate to reduced survival. Longer follow is important given the delay in therapy in those receiving curative therapy

    NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes

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    <p>Abstract</p> <p>Background</p> <p>Lipoteichoic acid (LTA) is a component of gram-positive bacterial cell walls and may be elevated in the cerebrospinal fluid of patients suffering from meningitis. Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Moreover, several studies have suggested that increased oxidative stress is implicated in the pathogenesis of brain inflammation and injury. However, the molecular mechanisms underlying LTA-induced redox signal and MMP-9 expression in brain astrocytes remain unclear.</p> <p>Objective</p> <p>Herein we explored whether LTA-induced MMP-9 expression was mediated through redox signals in rat brain astrocytes (RBA-1 cells).</p> <p>Methods</p> <p>Upregulation of MMP-9 by LTA was evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways were investigated by pretreatment with pharmacological inhibitors or transfection with small interfering RNAs (siRNAs), Western blotting, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover, we determined the cell functional changes by migration assay.</p> <p>Results</p> <p>These results showed that LTA induced MMP-9 expression via a PKC(α)-dependent pathway. We further demonstrated that PKCα stimulated p47<sup>phox</sup>/NADPH oxidase 2 (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9 promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co-activator p300 also contributed to these responses. Functionally, LTA-induced MMP-9 expression enhanced astrocytic migration.</p> <p>Conclusion</p> <p>These results demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(α)-mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell migration enhanced by LTA.</p

    Burden and modifications in life from the perspective of caregivers for patients after stroke

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    OBJECTIVE: to analyze the impact that caring has on a member of the family caring for a patient after a cerebrovascular accident, correlating life modifications and mental suffering with the perceived burden. METHOD: a cross-sectional, quantitative study, undertaken in January-April 2010 in Fortaleza, Ceará, Brazil. RESULT: 61 individuals were investigated, monitored by three hospitals' Home Care Program. Data collection was through interviews for identifying life changes, and through the application of three scales for investigating perceived burden, mental state and mental suffering. Respectively these were the Caregiver Burden Scale (CBS), the Mini-Mental State Examination (MMSE) and the Self Reported Questionnaire (SRQ). The majority of the carers were female, married, and the children of the stroke patients. The average age was 48.2 years (±12.4). The most-cited life modifications referred to the daily routine, to leisure activities, and to exhaustion or tiredness. Regarding burden, the dimensions of General tension, Isolation and Disappointment stood out. It was ascertained that overload was more severe when the carer presented more symptoms of psychological distress, in the absence of a secondary carer, and when the principal carers reported perceiving changes in their bodies and health. CONCLUSION: an association between burden and the carer's mental state was not observed. Understanding the care, through analysis of the burden and of the knowledge of the biopsychosocial situation will provide support for the nurse's work in reducing the overload for family caregivers.OBJETIVO: analizar el impacto del cuidar para el cuidador familiar de paciente después de accidente vascular cerebral, correlacionando modificaciones de vida y sufrimiento psíquico con la sobrecarga percibida. MÉTODO: estudio transversal, cuantitativo, realizado de enero a abril de 2010, en Fortaleza, Ceará, Brasil. RESULTADO: se investigaron 61 individuos, acompañados por el Programa de Servicio Domiciliar de tres hospitales. La colecta de los datos ocurrió mediante entrevista para identificar modificaciones de vida, y con la aplicación de tres escalas para investigar la sobrecarga percibida, estado mental y sufrimiento psíquico. Son ellas, respectivamente: Caregiver Burden Scale (CBS), Mini Examen del Estado Mental (MEEM) y Self Reported Questionnaire (SRQ). Los cuidadores, en su mayoría, eran del sexo femenino, casados (as) e hijo (as) de los pacientes después del AVC. Edad Media de 48,2 años (±12,4). Las modificaciones de vida más citadas fueron referentes a la rutina diaria, a las actividades de ocio y agotamiento o cansancio. En cuanto a la sobrecarga, se destacaron las dimensiones Tensión general, Aislamiento y Decepción. Se verificó mayor sobrecarga cuanto más síntomas de sufrimiento psíquico el cuidador presentase, en la ausencia de cuidador secundario y cuando los cuidadores principales relataron percibir modificación en el cuerpo y en la salud. CONCLUSIÓN: no fue observada asociación de la sobrecarga con el estado mental del cuidador. Entender la coyuntura del cuidado, mediante análisis del recargo de trabajo, y del conocimiento de la situación biopsicosocial, suministrará subsidios para la actuación del enfermero para reducir la carga generada para los cuidadores familiares.OBJETIVO: analisar o impacto do cuidar para o cuidador familiar de paciente após acidente vascular cerebral (AVC), correlacionando modificações de vida e sofrimento psíquico com a sobrecarga percebida. MÉTODO: estudo transversal, quantitativo, realizado de janeiro a abril de 2010, em Fortaleza, Ceará, Brasil. RESULTADO: investigaram-se 61 indivíduos, acompanhados pelo Programa de Atendimento Domiciliar (PAD), de três hospitais. A coleta dos dados ocorreu mediante entrevista para identificar modificações de vida, e com a aplicação de três escalas para investigar sobrecarga percebida, estado mental e sofrimento psíquico. São elas, respectivamente: Caregiver Burden Scale (CBS), Miniexame do Estado Mental (MEEM) e Self Reported Questionnaire (SRQ). Os cuidadores, na sua maioria, eram do sexo feminino, casados(as) e filho(as) dos pacientes após AVC. A média de idade era de 48,2 anos (±12,4). As modificações de vida mais citadas foram referentes à rotina diária, às atividades de lazer e esgotamento ou cansaço. Quanto à sobrecarga, destacaram-se as dimensões tensão geral, isolamento e decepção. Verificou-se maior sobrecarga quanto mais sintomas de sofrimento psíquico o cuidador apresentasse, na ausência de cuidador secundário e quando os cuidadores principais relataram perceber modificação no corpo e na saúde. CONCLUSÃO: não foi observada associação da sobrecarga com o estado mental do cuidador. Entender a conjuntura do cuidado, mediante análise da sobrecarga de trabalho, e do conhecimento da situação biopsicossocial fornecerá subsídios para a atuação do enfermeiro para reduzir a carga gerada para os cuidadores familiares

    The development and psychometric properties of the Arabic version of the child oral health impact profile-short form (COHIP- SF 19)

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    BACKGROUND: This study aims to cross-culturally adapt the original English-language COHIP-SF 19 to Arabic culture and to test its psychometric properties in a community sample. METHODS: The Arabic COHIP-SF 19 was developed and its psychometric properties were examined in a population-based sample of 876 schoolchildren who were aged 12 years of age, in Benghazi, Libya. The Arabic COHIP-SF 19 was tested for its internal consistency, reproducibility, construct validity, factorial validity and floor as well as ceiling effects. A Mann-Whitney U test was used to compare the mean scores of COHIP-SF 19 by participants' caries status and self-reported oral health rating, satisfaction and treatment need. RESULTS: The Arabic COHIP-SF 19 was successfully and smoothly developed. It showed an acceptable level of equivalence to the original version. Overall, the internal consistency and reproducibility were acceptable to excellent, with a Cronbach's alpha of 0.84 and an intra-class correlation coefficient (ICC) of 0.76. All hypotheses predefined to test construct validity were confirmed. That is, children who had active dental caries, and who rated their oral health as poor, were not satisfied with their oral health or indicated the need of treatment had lower COHIP-SF 19 scores (P < 0.05). Floor or ceiling effects were not observed. The exploratory Factorial analysis suggested a 4-component solution and deletion of one item. CONCLUSION: The Arabic COHIP-SF 19 was successfully developed. The measure demonstrated satisfactory reliability and validity to estimate OHRQoL in a representative sample of 12-year-old schoolchildren
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