511 research outputs found

    INFLAMMATORY GENE EXPRESSION IN WOMEN DIAGNOSED WITH POLYCYSTIC OVARIAN SYNDROME

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    Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS subjects (P\u3c0.01). BMI was found to significantly increase mRNA expression of TNFa and IL-1ß (PP\u3c0.05)

    Type-1 interferons contribute to oxygen glucose deprivation induced neuro-inflammation in BE(2)M17 human neuroblastoma cells

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    BACKGROUND: Hypoxic-ischaemic injuries such as stroke and traumatic brain injury exhibit features of a distinct neuro-inflammatory response in the hours and days post-injury. Microglial activation, elevated pro-inflammatory cytokines and macrophage infiltration contribute to core tissue damage and contribute to secondary injury within a region termed the penumbra. Type-1 interferons (IFNs) are a super-family of pleiotropic cytokines that regulate pro-inflammatory gene transcription via the classical Jak/Stat pathway; however their role in hypoxia-ischaemia and central nervous system neuro-inflammation remains unknown. Using an in vitro approach, this study investigated the role of type-1 IFN signalling in an inflammatory setting induced by oxygen glucose deprivation (OGD). METHODS: Human BE(2)M17 neuroblastoma cells or cells expressing a type-1 interferon-α receptor 1 (IFNAR1) shRNA or negative control shRNA knockdown construct were subjected to 4.5 h OGD and a time-course reperfusion period (0 to 24 h). Q-PCR was used to evaluate IFNα, IFNβ, IL-1β, IL-6 and TNF-α cytokine expression levels. Phosphorylation of signal transducers and activators of transcription (STAT)-1, STAT-3 and cleavage of caspase-3 was detected by western blot analysis. Post-OGD cellular viability was measured using a MTT assay. RESULTS: Elevated IFNα and IFNβ expression was detected during reperfusion post-OGD in parental M17 cells. This correlated with enhanced phosphorylation of STAT-1, a downstream type-1 IFN signalling mediator. Significantly, ablation of type-1 IFN signalling, through IFNAR1 knockdown, reduced IFNα, IFNβ, IL-6 and TNF-α expression in response to OGD. In addition, MTT assay confirmed the IFNAR1 knockdown cells were protected against OGD compared to negative control cells with reduced pro-apoptotic cleaved caspase-3 levels. CONCLUSIONS: This study confirms a role for type-1 IFN signalling in the neuro-inflammatory response following OGD in vitro and suggests its modulation through therapeutic blockade of IFNAR1 may be beneficial in reducing hypoxia-induced neuro-inflammation

    The comparative clinical course of pregnant and non-pregnant women hospitalised with influenza A(H1N1)pdm09 infection

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    Introduction: The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy.Methods: A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15-44 years, using univariate and multivariable techniques.Results: Of the 395 women aged 15-44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR?=?0.49 (95% CI: 0.30-0.82)), require supplemental oxygen on admission (OR?=?0.40 (95% CI: 0.20-0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR?=?0.93 (95% CI: 0.46-1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died.Conclusions: Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups

    The sixth giant? Environmental policy and the Labour government, 1945–51

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    The connections between social and environmental policies have a longer and more fertile history than is often appreciated. Ignoring that history is not just unfortunate in its own terms but may mean that we deprive ourselves of resources that could be useful in the future. Unfortunately, social policy histories avoid discussion of the natural environment, just as environmental histories avoid discussion of welfare services. This article therefore seeks to open up new debates and a new field of research. It focuses upon one of the key periods in the development of UK state welfare, the Labour government of 1945–51. It argues that Labour displayed an ambivalence toward the natural environment. Land nationalisation had long been an aspiration, but Labour drew back from its more radical ambitions. In policy terms, this gave rise to a dualism. Town and country planning became one of its enduring legacies, but more socialistic, redistributive measures fell by the wayside

    Z-to-E isomerization processes in reactions catalyzed by cyclometalated ruthenium alkylidenes

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    The Z-content of products generated in reactions catalyzed by adamantyl-activated Z-selective metathesis catalysts is at first very high but degrades at higher conversions. The degree to which this undesirable process occurs is dependent on both the substrate and catalyst structure. Studies of Z-to-E isomerization processes and methods of preventing them are explored. Furthermore, an interesting Fischer carbene species was found to affect these isomerization processes

    Metathesis and Decomposition of Fischer Carbenes of Cyclometalated Z-Selective Ruthenium Metathesis Catalysts

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    The addition of vinyl ethers to Z-selective, cyclometalated ruthenium metathesis catalysts generates Fischer carbene complexes. Although Fischer carbenes are usually thought to be metathesis inactive, we show that Fischer carbenes are metathesis active under certain circumstances. These species were found to decompose facilely to Ru hydride complexes, as identified by both experiment and computation. Since vinyl ethers are often used to quench metathesis reactions implementing Ru-based metathesis catalysts, their decomposition to hydrides can have a deleterious effect on the desired stereochemistry of the olefin product

    Metathesis and Decomposition of Fischer Carbenes of Cyclometalated Z-Selective Ruthenium Metathesis Catalysts

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    The addition of vinyl ethers to Z-selective, cyclometalated ruthenium metathesis catalysts generates Fischer carbene complexes. Although Fischer carbenes are usually thought to be metathesis inactive, we show that Fischer carbenes are metathesis active under certain circumstances. These species were found to decompose facilely to Ru hydride complexes, as identified by both experiment and computation. Since vinyl ethers are often used to quench metathesis reactions implementing Ru-based metathesis catalysts, their decomposition to hydrides can have a deleterious effect on the desired stereochemistry of the olefin product

    Pre-Admission Statin Use and In-Hospital Severity of 2009 Pandemic Influenza A(H1N1) Disease

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    In this group of patients hospitalized with pandemic influenza, a significant beneficial effect of pre-admission statin use on the in-hospital course of illness was not identified. Although the database from which these observations are derived represents the largest available suitable UK hospital cohort, a larger study would be needed to confirm whether there is any benefit in this setting
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