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Ultrawide area photo to be able to file the advancement of gyrate atrophy from the choroid as well as retina over Several years.
Given the underinvestment in global mental health to-date, it is important to consider how best to maximize the impact of existing investments. Theory of Change (ToC) is increasingly attracting the interest of funders seeking to evaluate their own impact. This is one of four papers investigating Grand Challenges Canada's (GCC's) first global mental health research funding portfolio (2012-2016) using a ToC-driven approach.

A portfolio-level ToC map was developed through a collaborative process involving GCC grantees and other key stakeholders. Proposed ToC indicators were harmonised with GCC's pre-existing Results-based Management and Accountability Framework to produce a "Core Metrics Framework" of 23 indicators linked to 17 outcomes of the ToC map. For each indicator relevant to their project, the grantee was asked to set a target prior to the start of implementation, then report results at six-month intervals. We used the latest available dataset from all 56 projects in GCC's global mental health fundinenges in setting appropriate targets, for example due to insufficient epidemiological evidence. Differences in delivery outcomes when disaggregated by disorder suggest that these challenges are not universal. We caution implementers, funders and evaluators from taking a one-size-fits all approach and make several recommendations for how to facilitate more in-depth, multi-method evaluation of impact using portfolio-level ToC.
Under- or over-achievement of targets may reflect operational challenges such as high staff turnover, or challenges in setting appropriate targets, for example due to insufficient epidemiological evidence. Differences in delivery outcomes when disaggregated by disorder suggest that these challenges are not universal. We caution implementers, funders and evaluators from taking a one-size-fits all approach and make several recommendations for how to facilitate more in-depth, multi-method evaluation of impact using portfolio-level ToC.Dopamine is a key neurotransmitter that regulates attention through dopamine D1 and D2-receptors in the prefrontal cortex (PFC). We previously developed an object-based attention test (OBAT) to evaluate attention in mice. Disruption of the dopaminergic neuronal system in the PFC induced attentional impairment in the OBAT. However, previous studies have not systematically examined which specific brain regions are associated with the blockade of PFC dopamine D1 and D2-receptors in the OBAT. see more In this study, we investigated the association of dopamine D1 and D2-receptors in the PFC with attention and neuronal activity in diverse brain regions. We found that both dopamine D1 and D2-receptor antagonists induced attentional impairment in the OBAT by bilateral microinjection into the PFC of mice, suggesting that both dopamine D1 and D2-receptors were associated with attention in the OBAT. Our analysis of the neuronal activity as indicated by c-Fos expression in 11 different brain regions showed that based on the antagonist types, there was selective activation of several brain regions. Overall, this study suggests that both dopamine D1 and D2-receptors play a role in attention through different neuronal circuits in the PFC of mice.
Lytic polysaccharide monooxygenases (LPMOs) are important industrial enzymes known for their catalytic degradation of recalcitrant polymers such as cellulose or chitin. Their activity can be measured by lengthy HPLC methods, while high-throughput methods are less specific. A fast and specific LPMO assay would simplify screening for new or engineered LPMOs and accelerate biochemical characterization.

A novel LPMO activity assay was developed based on the production of the dye phenolphthalein (PHP) from its reduced counterpart (rPHP). The colour response of rPHP oxidisation catalysed by the cellulose-specific LPMO from Thermoascus aurantiacus (TaAA9A), was found to increase tenfold by adding dehydroascorbate (DHA) as a co-substrate. The assay using a combination of rPHP and DHA was tested on 12 different metallo-enzymes, but only the LPMOs catalysed this reaction. The assay was optimized for characterization of TaAA9A and showed a sensitivity of 15nM after 30min incubation. It followed apparent Michaelis-Meand has the potential to characterize LPMO activity in industrial settings, where usual co-substrates such as ascorbate and oxygen are depleted.
This novel and specific LPMO assay can be carried out in a convenient microtiter plate format ready for high-throughput screening and enzyme characterization. DHA was the best co-substrate tested for oxidation of rPHP and this preference appears to be LPMO-specific. The identified co-substrates DHA and fructose are not normally considered as LPMO co-substrates but here they are shown to facilitate both oxidation of rPHP and degradation of cellulose. This is a rare example of a finding from a high-throughput assay that directly translate into enzyme activity on an insoluble substrate. The rPHP-based assay thus expands our understanding of LPMO catalysed reactions and has the potential to characterize LPMO activity in industrial settings, where usual co-substrates such as ascorbate and oxygen are depleted.
Lipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin.

14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients.
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