Activity

  • Temple Flood posted an update 6 days, 15 hours ago

    Neuroendocrine adrenal chromaffin cells release neurohormones catecholamines in response to Ca2+ entry via voltage-gated Ca2+ channels (VGCCs). Adrenal chromaffin cells also express non-voltage-gated channels, which may conduct Ca2+ at negative membrane potentials, whose role in regulation of exocytosis is poorly understood. We explored how modulation of Ca2+ influx at negative membrane potentials affects basal cytosolic Ca2+ concentration ([Ca2+]i) and exocytosis in metabolically intact voltage-clamped bovine adrenal chromaffin cells. We found that in these cells, Ca2+ entry at negative membrane potentials is balanced by Ca2+ extrusion by the Na+/Ca2+ exchanger and that this balance can be altered by membrane hyperpolarization or stimulation with an inflammatory hormone bradykinin. Membrane hyperpolarization or application of bradykinin augmented Ca2+-carrying current at negative membrane potentials, elevated basal [Ca2+]i, and facilitated synchronous exocytosis evoked by the small amounts of Ca2+ injected into the cell via VGCCs (up to 20 pC). Exocytotic responses evoked by the injections of the larger amounts of Ca2+ via VGCCs (> 20 pC) were suppressed by preceding hyperpolarization. In the absence of Ca2+ entry via VGCCs and Ca2+ extrusion via the Na+/Ca2+ exchanger, membrane hyperpolarization induced a significant elevation in [Ca2+]i and asynchronous exocytosis. Our results indicate that physiological interferences, such as membrane hyperpolarization and/or activation of non-voltage-gated Ca2+ channels, modulate basal [Ca2+]i and, consequently, segregation of exocytotic vesicles and their readiness to be released spontaneously and in response to Ca2+ entry via VGCCs. These mechanisms may play role in homeostatic plasticity of neuronal and endocrine cells. Propolis has been reported to possess rich content of antioxidant compounds and may provide health benefits through oxidative stress reduction. Presently, the formulation activities used to enhance the drug delivery have been hampered due to inherently low aqueous solubility and poor transdermal permeation of the bioactive phenols and flavonoids. Here, we show, the formulation of propolis extract (PE) into phytosome delivery systems. The optimum antioxidant activity was attained through extraction process using 75% v/v ethanol. The phytosome was prepared using thin-layer hydration technique with l-α-Phosphatidylcholine as a phospholipid. Fourier transform infrared (FTIR) was used to investigate the occurrence of molecular interactions between formulation components. This innovative approach could encapsulate >40% of bioactive compounds in PE, namely caffeic acid, quercetin, and kaempferol. FTIR spectroscopy indicated new hydrogen bond formation, supporting successful phytosome formulation. The phytosomes enhanced the dissolution up to 4-folds of bioactive compounds in bio-mimicked release media, as well as improved penetrability and skin retention up to 6-folds of the three main compounds of propolis, when compared to non-encapsulated PE formulation. Importantly, the hydrogel containing phytosome showed a potential for UVA and UVB radiation absorption, indicated by the SPF values of higher than 15. To conclude, this work shows promising novel delivery approaches for PE in the treatment of organ injured stress oxidative and skin aging. The relationship between sense of agency and sense of ownership remains unclear. Here we investigated this relationship by manipulating ownership using the rubber hand illusion and assessing the resulting impact on self-experiences during the vicarious agency illusion. We tested whether modulating ownership towards another limb using the rubber hand illusion would subsequently influence the illusory experience of ownership and agency towards a similar-looking limb in the vicarious agency task. Crucially, the vicarious agency task measures both sense of agency and sense of ownership at the same time, while removing the confounding influence of motor signals. Our results replicated the well-established effects of both paradigms. We also found that manipulating the sense of ownership with the rubber hand illusion influenced the subsequent vicarious experience of ownership but not the vicarious experience of agency. This supports the idea that sense of agency and sense of ownership are, at least partially, independent experiences. The objective of this case-control study was to determine the herd- and cow-level risk factors associated with an outbreak of Mycoplasma bovine mastitis in the winter of 2014-2015 in Nemuro, Hokkaido, Japan. Two questionnaire surveys were sent to all 40 Mycoplasma-infected farms in the area and 73 non-infected farms for the farm-level analysis. Infected cows were matched to twice the number of non-infected cows in the same herds by parity and days after calving. Movement records, dairy herd test records, and clinical records of infected cows and matched non-infected cows were collected for the cow-level analysis. Risk factors for Mycoplasma infection were explored by multivariable analyses at both levels. In the herd-level analysis, tie stall housing for milking cows (odds ratio [OR] = 0.20, 95 % confidence interval [CI] 0.07-0.60, p =  0.004), consciously wiping of teat openings before milking (OR = 0.15, 95 % CI 0.02-0.76, p =  0.030), and use of paper towels to wipe teats (OR = 0.31, 95 % CI 0.09-0.92, p =  0.045) were identified as preventive factors, whereas introduction of cattle (OR = 3.43, 95 % CI 1.14-10.86, p =  0.030) was identified as a risk factor. In the cow-level analysis, a history of presence in livestock markets (OR = 10.80, 95 % CI 1.12-104.38, p =  0.040), higher milk yield 2 months prior to Mycoplasma infection (OR = 1.09, 95 % CI 1.02-1.18, p =  0.014), and previous diagnosis of acute mastitis without isolation of the causal pathogen (OR = 3.14, 95 % CI 0.86-11.41, p =  0.082) were identified as risk factors. These results highlight the importance of proper milking hygiene control and quarantine of introduced cattle to prevent Mycoplasma infection. RATIONALE It is important to investigate the diversity and variability among adverse childhood experiences (ACEs) in young mothers because they are likely to experience considerable adverse exposures during childhood as well as challenging environments following childbirth. Pidnarulex cell line OBJECTIVE The current study used latent class analysis with a diverse sample of young mothers to identify subgroups of mothers based on their adverse childhood experiences (ACEs). Subsequent analyses were conducted to examine class specific differences in maternal mental health postpartum and their children’s socio-emotional functioning at eight years of age. RESULTS Four classes of participants were identified based on mothers’ ACEs, including a high, multiple-risk class, a low-risk class, a high-risk for abuse class, and a high-risk for household dysfunction class. These classes were associated with differences in maternal and child functioning. The low-risk class showed significantly better maternal and child health and well-being than the high-risk class. However, nuanced differences were seen for mothers and their children across all classes; for example, children of mothers in the high-risk for abuse class scored significantly better on internalizing behaviors than children from the high, multiple-risk class, but not better on externalizing behaviors. Further, children of mothers in the high-risk for household dysfunction class scored better than the high, multiple-risk class on externalizing behaviors but not better on scores of internalizing behaviors. CONCLUSION Understanding the differences in how certain types of childhood adversity are associated with mothers’ and their children’s later health and well-being will bolster the use of only a sum score of ACEs for both how we research risk and in supporting clinicians to provide targeted care. Public health scholars have increasingly called for greater attention to the political and policy processes that enable or constrain successful prioritisation of health on government agendas. Much research investigating policy agenda-setting in public health has focused on the use of single frameworks, in particular Kingdon’s Multiple Streams Framework. More recently, scholars have argued that blending complementary policy frameworks can enable greater attention to a wider range of drivers that influence government agendas away from or towards progressive social and health policies. In this paper, we draw on multiple policy process frameworks in a study of agenda-setting for Australia’s first national paid parental leave scheme. Introduced in 2011 after decades of advocacy, this scheme provides federal government-funded parental leave for eighteen weeks’ pay at the minimum wage for primary caregivers, with evaluations showing improved health and equity outcomes. Drawing on empirical data collected from documentary sources and interviews with 25 key policy informants, we find that a combination of policy frameworks; in this case, Kingdon’s Multiple Streams; Advocacy Coalition Framework; Punctuated Equilibrium; Narrative Policy Framework; and Policy Feedback helped explain how this landmark social policy came about. However, none of these frameworks were adequate without situating them within a critical feminist lens which enabled an explicit focus on the gendered nature of power. We argue that, alongside making use of policy process frameworks, social determinants of health policy research needs to engage with critical frameworks which share an explicit agenda for improving people’s daily living conditions and the re-distribution of power, money, and resources in ways that promote health equity. Great gains have been made in providing researchers geo-spatial data that can be combined with population health data. This development is crucial given concerns over the human health outcomes associated with a changing climate. Merging population and environmental data remains both conceptually and technically challenging because of a large range of temporal and spatial scales. Here we propose a framework that addresses and advances both conceptual and technical aspects of population-environment research. This framework can be useful for considering how any time or space-based environmental occurrence influences population health outcomes and can be used to guide different data aggregation strategies. The primary consideration discussed here is how to properly model the space and time effects of environmental context on individual-level health outcomes, specifically maternal, child and reproductive health outcomes. The influx of geospatial health data and highly detailed environmental data, often at daily scales, provide an opportunity for population-environment researchers to move towards a more theoretically and analytically sound approach for studying environment and health linkages. INTRODUCTION Next-generation sequencing (NGS) based on genomic DNA has been widely applied for gene rearrangement detection in patients with non-small cell lung cancer (NSCLC). However, intergenic-breakpoint fusions, in which one or both genomic breakpoints localize to intergenic regions, confound kinase fusion detection. We evaluated the function of intergenic-breakpoint fusions with multiplex molecular testing approaches. METHODS NSCLCs with intergenic-breakpoint fusion identified by DNA-based NGS were analyzed by RNA-based NGS, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). RESULTS Twenty-six cases with single intergenic-breakpoint fusion were identified from a large cohort of NSCLCs using DNA-based NGS. Of the 26 cases, RNA-based NGS detected expressed fusion transcripts in 11 cases, and the genomic breakpoint position did not logically predict breakpoint of the fusion transcript in these cases, possibly due to complex rearrangements (n=5), alternative splicing (n=2) and reciprocal rearrangement (n=4).