Aldosterone and the cardiovascular complications of chronic kidney disease

Cardiac mortality and morbidity is a significant problem in the renal failure population. For some, their renal dysfunction is a consequence of their cardiac failure or general vascular disease; for others it develops and progresses over the course of their renal disease. Uraemic Cardiomyopathy is a group of particular cardiac abnormalities that are found in renal failure; left ventricular hypertrophy, ventricular dilatation and left ventricular systolic dysfunction. Left ventricular hypertrophy is the commonest of these and occurs in 75% of those starting dialysis. Pathological examination of these hearts reveals prominent cardiac fibrosis and expansion of the ventricular muscular wall. Uraemic cardiomyopathy is more common as renal function deteriorates but doesn’t occur in all patients requiring renal replacement therapy. Therefore it has been proposed that factors other than uraemia and uraemic toxins probably contribute to this pathological process. The renin-angiotensin-aldosterone system is one of the possible contributing factors. Animal studies and more recently clinical studies have added weight to this theory. Brilla and Weber published a set of landmark papers in 1992, demonstrating an increase in cardiac fibrosis in rats treated with an aldosterone infusion. However, these finding were only present in rats fed a high sodium diet. They also appear to be independent of hypertension; another known cause of left ventricular hypertrophy. Evidence in humans is more difficult to prove and remains varied in outcome. A recent study in a hypertensive population found a positive correlation between aldosterone serum levels and left ventricular mass. Evidence in renal failure is even more limited and it is this situation that we have focused on in our study. Transforming growth factor beta is a proposed down-stream signalling molecule of the renin-angiotensin-aldosterone system in cardiac fibrosis/left ventricular hypertrophy. However this is not the only signalling pathway that is under investigation and at present the evidence is equivocal. This Thesis incorporates three separate but related studies. The West of Scotland Kidney Disease Study was a 10 year follow-up analysis of patients initially enrolled in 2005, with a range of renal failure from mild to end-stage, those on dialysis and transplanted patients. As expected survival decreased as renal function declined and survival rates were better in the transplanted group than those on dialysis. However, survival rates in this group of patients were not determined by aldosterone, total renin, aldosterone:renin ratio, left ventricular mass or ejection fraction. Our study did confirm previous evidence that urinary protein excretion greater than 1 g/day was associated with a significant increase in mortality over the 10 year follow-up. The Aldosterone Study, aimed to identify factors affecting left ventricular mass and aldosterone levels in a renal failure population. Unfortunately no link was identified between aldosterone and left ventricular mass, or surrogate markers of cardiac disease. Also no significant factors affecting the aldosterone levels of these patients were identified. The Rat Slice Study was an experimental model developed in an attempt to replicate ventricular cell interactions and structure that occurs within the body. Rat ventricle tissue slices were used and incubated in media for 48hours. The media was supplemented with different concentrations of aldosterone, water or both to determine the effects of aldosterone and sodium concentration on TGF-β1 production and cardiac fibrosis. Viability of the slices was evident at 48hours although at a much lower level than at the start of the experiment. No increase in cardiac fibrosis or TGF-β1 production was found in any of the groups of tissue slices. In Conclusion, the three studies undertaken found no definitive evidence for the role of aldosterone or TGF-β1 in cardiac fibrosis/left ventricular hypertrophy. This was true of both the uraemic and non-uraemic states

Fabrication of the Unknown

In fire there is passion, possibility and transformation. I find beauty in my embarrassment. I welcome the silly. If the objects I make want a rat-tail, like a boy, I let them have it. I have found throughout my life that what I resist the most persists. The more I pushed away from making vessels, the more prominent they became in my practice. They are important to me and I am not really sure why, being that when I was growing up handmade objects were not revered. I have certain obsessive-compulsive tendencies. I like to repeat myself. With this notion declared I feel like I have found a bit of understanding in why I make functional objects. Through repetition I make formal inquiries into familiar things. I have an intimate relationship to objects of all kinds. My dad is a collector of sorts and as a result of being his daughter I collect and form emotional attachments to inanimate objects too. I remember the day our microwave died. It felt like a pet dying. I felt that deep ache in my heart and insisted on taking pictures with it as it sat on the curb to be taken away by the junk men. This brings me to a very important point about when things are out of sight and die; essentially we can forget them but the memory is what makes the ache come back. The physical act of painting brings up memories that I have forgotten a long time ago like a fight with my sister or walking home with freezing cold feet from playing in the creek in January. Sometimes I just think of smells like the smell of my Mom's perfume or the way the old Minyards grocery store smelled just up the street from my house growing up. I long for moments in the past even though it puts me in a somber mood. As a maker of objects, I am making the impermanent, permanent.</p

Pomegranate extract supplementation on neuromuscular performance during resistance exercise

Dietary nitrate supplementation has been shown to improve skeletal muscle function during high-velocity and high-power contractions due to its high nitrate levels; however, there is limited data examining its potential in exercise requiring these movements, such as resistance exercise. Nitrate supplementation has been studied extensively as beetroot juice, but its poor taste severely limits its application. Pomegranate extract (POM) may be an alternative nitrate source due to its superior taste, high nitrate content, and additional antioxidants but has yet to be explored. The purpose of the present study is two-fold: 1) to determine the nitrate concentration in POM; and 2) to examine the effect of POM supplementation on neuromuscular performance during resistance exercise. In phase 1, the concentration of nitrate in commercially available pomegranate products was quantified to guide dosing regimens for phase 2. During Phase 2, in a double-blind, randomized, crossover design, 15 healthy recreationally active males and females will arrive to the laboratory for 5 visits over 3-4 weeks. Participants will perform a one repetition maximum test followed by a familiarization to the protocol. Following this, participants will perform 3 experimental conditions by consuming: 1) empty capsules containing negligible nitrate (PL); 2) a conventional dose of nitrate (POM-NORM, 9 mmol of nitrate); and 3) a high dose of nitrate (POM-HIGH, 13.5 mmol of nitrate) ~2.5 hours prior to exercise testing. During experimental visits, a resting blood draw will be obtained, then subjects will perform a protocol for determining power during countermovement jumps, kneeling countermovement pushups, and back squats. Muscle power will be determined by using a force plate and linear transducer. Results for Phase 1 of the study showed that POM extract contained 2.2 mmol of nitrate per gram of the 200 mg/mL extract. Therefore, it is recommended that participants ingest 6 capsules for 9 mmol of nitrate or 9 capsules for 13.5 mmol of nitrate. Phase 2 is in the data collection phase and ongoing

Exploring UK doctors’ attitudes towards online patient feedback : thematic analysis of survey data

Introduction: Patients are increasingly using online platforms to give feedback about their health-care experiences. Online feedback has been proposed as a way to drive transformative change in the health service through informing choice and improving quality. Attitudes held by health-care professionals influence the uptake of new technologies. Understanding these attitudes is essential in exploring the potential of online patient feedback as a standard feedback mechanism. This study explores the content of free-text comments left by doctors responding to a survey with the aim of understanding their attitudes towards online feedback. Methods: A cross-sectional online questionnaire was completed by 1001 UK primary and secondary-care doctors. Doctors were given the opportunity to leave a free-text comment about online patient feedback. Doctors’ attitudes towards online patient feedback were identified and explored using thematic analysis. Descriptive statistics and chi-square tests were used to examine demographic differences between those doctors who left a comment and those who did not. Results: Thematic analysis identified five key interrelated themes: anonymity, confidentiality, representativeness, moderation/regulation of online feedback and platform type. The characteristics of those leaving a comment very closely matched those of the entire survey sample. Conclusion: Across the comments, the most prominent finding was a general scepticism and caution towards online feedback, with most of the key themes relating to the perceived limitations and challenges. Further work exploring ways of addressing and verifying online comments without breaching confidentiality could provide valuable information to health systems seeking to drive improvement through patient online feedback

In vitro rooting of regenerants of blue poplar

The article presents the research results of the influence of hormonal composition of the culture medium and cultivation duration on regenerants of Populus pruinosa at the stage of rooting in vitro. 98,3±1,7 % of regenerants rooted on MS culture medium with 1,0 mg L−1 IMА during 8 weeks of cultivation.Приведены результаты исследований влияния гормонального состава питательной среды и длительности культивирования на растения-регенеранты тополя сизолистного на этапе укоренения in vitro; 98,3±1,7 % регенерантов укоренялись на питательной среде МС, дополненной 1,0 мг/л ИМК, в течение 8 недель культивирования

What explains the link between childhood ADHD and adolescent depression? Investigating the role of peer relationships and academic attainment

There is increasing evidence that childhood Attention-Deficit Hyperactivity Disorder (ADHD) elevates risk of later depression, but the mechanisms behind this association are unclear. We investigated the relationship between childhood ADHD symptoms and late-adolescent depressive symptoms in a population cohort, and examined whether academic attainment and peer problems mediated this association. ALSPAC (Avon Longitudinal Study of Parents and Children) is an ongoing prospective longitudinal population-based UK cohort that has collected data since September 1990. 2950 individuals with data on parent-reported ADHD symptoms in childhood (7.5 years) and self-reported depressive symptoms in late adolescence (17.5 years) were included in analyses. 2161 individuals with additional data at age 16 years on parent-reported peer problems as an indicator of peer relationships and formal examination results (General Certificate of Secondary Education; GCSE) as an indicator of academic attainment were included in mediation analyses. Childhood ADHD symptoms were associated with higher depressive symptoms (b = 0.49, SE = 0.11, p < 0.001) and an increased odds of clinically significant depressive symptoms in adolescence (OR = 1.27, 95% CI 1.15–1.41, p < 0.001). The association with depressive symptoms was mediated in part by peer problems and academic attainment which accounted for 14.68% and 20.13% of the total effect, respectively. Childhood ADHD is associated with increased risk of later depression. The relationship is mediated in part by peer relationships and academic attainment. This highlights peer relationships and academic attainment as potential targets of depression prevention and intervention in those with ADHD. Future research should investigate which aspects of peer relationships are important in conferring later risk for depression

YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria.

Mitochondria contain their own translation apparatus which enables them to produce the polypeptides encoded in their genome. The mitochondrially-encoded RNA components of the mitochondrial ribosome require various post-transcriptional processing steps. Additional protein factors are required to facilitate the biogenesis of the functional mitoribosome. We have characterized a mitochondrially-localized protein, YbeY, which interacts with the assembling mitoribosome through the small subunit. Loss of YbeY leads to a severe reduction in mitochondrial translation and a loss of cell viability, associated with less accurate mitochondrial tRNASer(AGY) processing from the primary transcript and a defect in the maturation of the mitoribosomal small subunit. Our results suggest that YbeY performs a dual, likely independent, function in mitochondria being involved in precursor RNA processing and mitoribosome biogenesis. Issue Section: Nucleic Acid Enzymes

Co-Ingestion of Dietary Nitrate and Ascorbic Acid on Nitric Oxide Biomarkers and The Oral Microbiome in Sedentary Hispanic Women

Nitric oxide bioavailability increases following nitrate supplementation wherein oral microbiota facilitate the metabolism and absorption of nitrate. However, few studies have examined if co-ingestion of nitrate with antioxidants can further elevate nitric oxide bioavailability. Moreover, our understanding on how the oral microbiome responds to nitrate supplementation is limited, especially in women. PURPOSE: To examine the effects of ingesting dietary nitrate and ascorbic acid independently and concurrently on markers of nitric oxide bioavailability and oral microbiota species. METHODS: Twelve sedentary women of Hispanic descent (mean ± SD: age 20 ± 1 years; body mass 74 ± 15 kg; height 1.62 ± 0.09 m) consumed nitrate-rich beetroot juice (BR), nitrate-depleted beetroot juice (PL), ascorbic acid (AA), and crystal light (CRY) in four conditions: BR combined with AA (BR+AA); BR only (BR+CRY); AA only (PL+AA); and placebo-control (PL+CRY). Supplements were ingested 2.5 hours prior to a resting blood draw and buccal swab sample. Plasma [nitrate] and [nitrite] were analyzed using gas phase chemiluminescence. Buccal swab samples were used for DNA extraction and isolation. DNA was amplified using polymerase chain reaction (PCR) targeting the V3 - V4 region of the 16S rRNA gene. Following index PCR, amplicons were pooled and sequenced using the iSeq Illumina NGS sequencer. Reads were clustered into amplicon sequence variants and analyzed for alpha and beta diversity and relative abundance. RESULTS: BR increased plasma [nitrate] (BR+AA: 641 ± 252 vs. BR+CRY: 528 ± 307 vs. PL+AA: 35 ± 10 vs. PL+CRY: 35 ± 12 µM, P \u3c 0.001) and plasma [nitrite] (BR+AA: 710 ± 336 vs. BR+CRY: 578 ± 428 vs. PL+AA: 209 ± 88 vs. PL+CRY: 198 ± 82 nM, P \u3c 0.001) with no differences within BR and PL conditions. Alpha and beta diversity, and the relative abundance of higher and lower taxonomic levels were not significantly different between all conditions (P \u3e 0.05) CONCLUSION: Concurrent nitrate and AA supplementation did not elicit additional increases to nitric oxide compared to nitrate ingestion alone. Acute beetroot juice and ascorbic acid were ineffective at modulating oral microbial composition. Further research is required to understand the impact of supplementation regimen and population on the physiological effects of dietary nitrate

Nest choice in arboreal ants is an emergent consequence of network creation under spatial constraints

Biological transportation networks must balance competing functional priorities. The selforganizing mechanisms used to generate such networks have inspired scalable algorithms to construct and maintain low-cost and efficient human-designed transport networks. The pheromone-based trail networks of ants have been especially valuable in this regard. Here, we use turtle ants as our focal system: In contrast to the ant species usually used as models for self-organized networks, these ants live in a spatially constrained arboreal environment where both nesting options and connecting pathways are limited. Thus, they must solve a distinct set of challenges which resemble those faced by human transport engineers constrained by existing infrastructure. Here, we ask how a turtle ant colony’s choice of which nests to include in a network may be influenced by their potential to create connections to other nests. In laboratory experiments with Cephalotes varians and Cephalotes texanus, we show that nest choice is influenced by spatial constraints, but in unexpected ways. Under one spatial configuration, colonies preferentially occupied more connected nest sites; however, under another spatial configuration, this preference disappeared. Comparing the results of these experiments to an agent-based model, we demonstrate that this apparently idiosyncratic relationship between nest connectivity and nest choice can emerge without nest preferences via a combination of self-reinforcing random movement along constrained pathways and density-dependent aggregation at nests. While this mechanism does not consistently lead to the de-novo construction of low-cost, efficient transport networks, it may be an effective way to expand a network, when coupled with processes of pruning and restructuring