1,783 research outputs found

    Composition of volatile compounds in bovine milk heat treated by instant infusion pasteurization and correlation to sensory analysis

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    Volatile compounds in skim milk and nonstandardised milk subjected to instant infusion pasteurisation at 80°C, 100°C and 120°C were compared with raw milk, high temperature short time pasteurised milk and milk pasteurised at 85°C/30 s. The composition of volatile compounds differed between infusion pasteurisation treated samples and the reference pasteurisations. The sensory properties of skim milk subjected to instant infusion pasteurisation were described by negative attributes, such as cardboard sour and plastic flavours, which are not associated normally with fresh milk. Partial least squares modelling showed good correlation between the volatile compounds and the sensory properties, indicating the predictive and possible causal importance of the volatile compounds for the sensory characteristics

    Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation

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    AbstractCurrent antiretroviral therapy (ART) for HIV/AIDS slows disease progression by reducing viral loads and increasing CD4 counts. Yet ART is not curative due to the persistence of CD4+ T-cell proviral reservoirs that chronically resupply active virus. Elimination of these reservoirs through the administration of synergistic combinations of latency reversing agents (LRAs), such as histone deacetylase (HDAC) inhibitors and protein kinase C (PKC) modulators, provides a promising strategy to reduce if not eradicate the viral reservoir. Here, we demonstrate that largazole and its analogues are isoform-targeted histone deacetylase inhibitors and potent LRAs. Significantly, these isoform-targeted HDAC inhibitors synergize with PKC modulators, namely bryostatin-1 analogues (bryologs). Implementation of this unprecedented LRA combination induces HIV-1 reactivation to unparalleled levels and avoids global T-cell activation within resting CD4+ T-cells.</jats:p

    Impact of postmenopausal vaginal discomfort on sex and relationships in Brazil: the CLOSER survey.

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    The CLOSER (CLarifying Vaginal Atrophy's Impact On SEx and Relationships) survey investigated how postmenopausal vaginal atrophy (VA) affects relationships between Brazilian women and male partners.Postmenopausal women (age 55-65 years) with VA, and male partners of women with the condition, completed an online survey on the impact of VA and local estrogen treatment on intimacy and relationships.A total of 360 women and 352 men from Brazil were included. Women (83%) and men (91%) reported that they were comfortable discussing VA with their partners. Women's key source of information on VA was health-care providers (HCPs), but 44% felt that not enough information is available. VA caused 70% of women to avoid sexual intimacy and resulted in less satisfying sex. VA had a negative impact on women's feelings and self-esteem. Women (76%) and men (70%) both reported that treatment with vaginal estrogen improved their sexual relationship, primarily by alleviating women's pain during sex. Women (56%) and men (59%) felt closer to each other after treatment.VA had a negative impact on sexual relationships for both women and men in Brazil, and reduced women's self-confidence. Vaginal hormone therapy improved couples' sexual relationships. A proactive attitude of HCPs is essential to educate women on VA and the potential benefits of treatment

    The double [3+2] photocycloaddition reaction

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    One of a synthetic organic chemists‟ greatest challenges is to create step-efficient routes toward compounds with high molecular complexity. Therefore, reactions such as the meta photocycloaddition of an olefin to a benzene derivative, which provide more than one bond in a single step are of significant importance. It this remarkable reaction three new σ bonds, three new rings and up to six new stereocenters are formed simultaneously. Additional complexity can be added by tethering the two reacting partners together and this form of the reaction has found many uses in natural product synthesis. In this work a remarkable double [3+2] photocycloaddition reaction is reported that results in the formation of a complex cis, cis, cis, trans-[5, 5, 5, 5] fenestrane derivative from a simple flat aromatic acetal with two branching alkenes. During this dramatic transformation four carboncarbon bonds, five new rings and seven new stereocenters are created in a single one-pot process using only UV light. The reaction occurs in a sequential manner from the linear meta photocycloadduct, via a secondary [3+2] addition of the alkene across the cyclopropane of the adduct. In addition, an angular meta photocycloadduct also produced in the initial addition step, undergoes an alternative fragmentation-translocation photoreaction to afford a silphinene-like angular tricyclic compound. In this work the investigation of this newly discovered process is discussed via the synthesis and subsequent irradiation of a series of photosubstrates containing different functional groups in the arene-alkene tether. In addition, attempts toward the synthesis of alternative structures using the same double [3+2] photocycloaddition are reported

    Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease.

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    Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≄1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P < 1 × 10(-7)), and significant grey matter loss and whole brain atrophy occurs annually (P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity
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