Homeostatic regulation has been shown to restore cortical activity in vivo following sensory deprivation, but it is unclear whether this recovery is uniform across all cells or specific to a subset ...of the network. To address this issue, we used chronic calcium imaging in behaving adult mice to examine the activity of individual excitatory and inhibitory neurons in the same region of the layer 2/3 monocular visual cortex following enucleation. We found that only a fraction of excitatory neurons homeostatically recover activity after deprivation and inhibitory neurons show no recovery. Prior to deprivation, excitatory cells that did recover were more likely to have significantly correlated activity with other recovering excitatory neurons, thus forming a subnetwork of recovering neurons. These network level changes are accompanied by a reduction in synaptic inhibition onto all excitatory neurons, suggesting that both synaptic mechanisms and subnetwork activity are important for homeostatic recovery of activity after deprivation.
•In adult cortex, a subset of excitatory neurons recover activity after enucleation•Inhibitory neurons do not homeostatically recover activity over 72 hr•Excitatory neurons recover in subnetwork specific manner•Recovery of activity is facilitated by reduced synaptic inhibition
Barnes et al. examine homeostatic recovery of activity of individual excitatory and inhibitory neurons in the adult cortex following enucleation. A fraction of excitatory neurons recover activity, in a subnetwork specific manner, but inhibitory cells do not recover activity over 72 hr.
Approximately 250,000 heart valve operations are performed annually worldwide. An intensive research and development effort has led to progressively more advanced heart valve prostheses. The ...Carpentier-Edwards Perimount Magna Ease (CEPME) prosthesis represents the latest iteration of the Edwards Perimount series of aortic tissue valves. The current study aims to evaluate the midterm performance of this bioprosthesis.
Five hundred and eighteen patients with aortic stenosis underwent aortic valve replacement with the CEPME valve at Papworth Hospital between August 2008 and November 2011. After a minimum of 3 years from the index operation, eligible patients were retrospectively and consecutively recruited to participate. Recruitment was closed after 100 eligible patients had completed all study assessments. Investigations at follow-up included echocardiography, and NYHA status. Primary endpoints included valve performance measures.
The mean age was 72 years, 64% were male and median follow-up was 5.1 years. NYHA status had improved in 66% of patients. The average postoperative peak and mean pressure gradients decreased by 51.2 mmHg (64.5%) and 31.8 mmHg (59.4%), with a significant improvement in NYHA status. The frequency of moderate aortic regurgitation was 3%. There was no evidence for structural valve deterioration.
The CEPME has excellent mid-term durability. Its use effectively improves haemodynamics and functional capacity.
Deliberative methods to assess ecosystem services values formalize community members’ and stakeholders’ involvement in decision-making related to natural resources management. This paper presents the ...methodological design and the application of a deliberative multicriteria evaluation (DMCE) method that combines the advantages of deliberation with structured decision-making to assess community-based values of four coastal ecosystem services (valued by indicators such as Total Nitrogen, Blue Carbon, Scallop Landings, Fish Abundance) and explore the spatial variability of group values along the Massachusetts coastline. We implemented four virtual deliberative workshops consisting of stakeholders from four Massachusetts Bays (MassBays) estuarine categorizations to collect quantitative and qualitative data. Quantitative data came from individual survey results and group preferences, while qualitative data were derived through the analysis of video recordings and transcripts of deliberations. Compared to previous studies, we combined quantitative and qualitative data by using applied thematic and co-occurrence analysis to identify themes of discussion during the deliberative process. Our results show that coastal stakeholders place a particular emphasis on access to clean water and services that directly support human wellbeing and provide direct economic benefits. Differences in the quantitative and qualitative results of these deliberative tasks between groups provide insight into the need for localized policymaking instead of solely regional or statewide management. Environmental managers and policymakers will utilize these insights to address local values and priorities as they work towards implementing habitat restoration efforts.
Abstract
Background and Aims
Inflammation induced by haemodialysis (HD) treatment has been recognised for several decades. Despite significant advances in technology, there is evidence that ...incompatibility between the dialyser, a foreign surface, and the patients’ blood, results in activation of the immune system. With each session, blood-membrane interaction leads to a repetitive activation of the innate complement system and a subsequent inflammatory response. It is now widely acknowledged that the consequences of long-term inflammation include fibrosis and accelerated cardiovascular disease, a common cause of mortality in patients with renal failure.
The aim of the CompAct-HD trial is to characterize complement activation and biomarker response to blood-membrane-circuit interaction during HD.
Method
For a single session, six timed intradialytic blood samples were collected from HD patients during standard treatment with ultrapure water and high flux “biocompatible” membranes. Complement activity potential was determined from timepoint 1 and inflammatory biomarkers from timepoints 2 to 6. Single time point samples were also collected from 7 healthy donors.
Highly multiplexed assays enabled to determine 30 biomarkers of inflammation, including cytokines, chemokines, growth factors and complement proteins, from a single blood sample.
Data analysis was performed using Microsoft® Excel Version 16.80 and GraphPad Prism 10.1.0.
Results
354 patients were recruited from 8 dialysis units across Greater Manchester, UK. An interim analysis was performed on 150 HD patients receiving standard care as well as 7 healthy donors.
Dialysis appears to generate an acute inflammatory response, that is, within 15 minutes of commencing treatment which does not appear to resolve by the end of the session.
This heightened inflammatory state was observed in HD patients in comparison to healthy donors (Fig. 1) with most pronounced changes seen in cytokines IL-1β, IL-10, IL-12p40 and TNF-α during dialysis. Established markers such as IL-6 also showed a 6-fold increase at the 75th percentile. Similarly, an exaggerated intradialytic response was observed in complement proteins, including the terminal complement complex (TCC) C5b-9 and anaphylatoxin C5a with spikes of up to 7-fold and 10-fold respectively (Fig. 2).
A session of HD was shown to cause a relative increase in complement proteins and inflammatory biomarkers. The magnitude of response seen in patients was variable (Fig. 3) with the greatest rise seen in the top quartile (above the Q3 boundary).
Conclusion
Our findings evidence a sharp inflammatory response to modern day HD treatment across a large cohort of dialysis patients. When compared to healthy donors, we observed heightened levels of inflammation in dialysis patients that is further exacerbated with each treatment session.
This study shows that HD has a significant role to play in the chronic inflammatory state of patients with end stage renal failure. Furthermore, here we describe potential targets, in both cytokine and complement proteins, which could be the key to downregulation of inflammation. Using targeted therapeutics, we have an opportunity to deliver a more biocompatible treatment, improving patient outcomes.
Indigenous leaders remain concerned that systemic oppression and culturally unsafe care impede Indigenous peoples living with HIV from accessing health services that make up the HIV cascade of care. ...We conducted a systematic review to assess the evidence related to experiences of the HIV care cascade among Indigenous peoples in Australia, Canada, New Zealand, and United States. We identified 93 qualitative and quantitative articles published between 1996 and 2017 reporting primary data on cascade outcomes disaggregated by Indigenous identity. Twelve involved data from Australia, 52 from Canada, 3 from New Zealand and 26 from United States. The majority dealt with HIV testing/diagnosis (50). Relatively few addressed post-diagnosis experiences: linkage (14); retention (20); treatment initiation (21); adherence (23); and viral suppression (24). With the HIV cascade of care increasingly the focus of global, national, and local HIV agendas, it is critical that culturally-safe care for Indigenous peoples is available at all stages.
Harmful algal blooms have become an increasingly significant threat to the health of global water bodies in recent decades. The Lower Charles River (LCR) has experienced large-scale blooms every year ...for the last decade despite largely successful efforts by regulatory agencies to reduce nutrient inputs. Algal blooms pose a threat to both local ecosystems and local communities; reduced access to recreation resulting from more frequent water safety advisories has a direct impact on human well-being and the overall perception of the region. To better understand the interactions between human activity and the variables that dictate algal growth, this work revolves around the creation of a system dynamics model with three sectors: phosphorous inputs to the study area, cyanobacteria growth patterns, and human well-being. The utility of this model is two-fold: (i) understanding the magnitude of influence certain variables have on other parts of the system provides valuable insights into how to best prevent or reduce the prevalence of harmful algal blooms in the study area and (ii) translation of the model into a user-friendly interface provides a tool with the potential to both raise general awareness and clearly communicate the issues at play to policymakers and the general public. Previous work modeling algal blooms focused primarily on ecological data without including quantified metrics of how the human experience may be impacted. The model presented here is unique in its use of proxies to indicate human well-being as a quantifiable variable. Initial findings include the degree to which certain inputs of phosphorous influence the presence and growth rates of cyanobacteria, the effects population growth and associated changes in land use have on the amount of phosphorous contributed to the system, and how cyanobacteria levels directly impact the percentage of the year residents and visitors can safely practice normal usage patterns.
A method is reported for the analysis of sterigmatocystin in various food and feed matrices using a commercial sterigmatocystin immunoaffinity column (IAC) for sample clean-up prior to HPLC analysis ...by UV with mass spectrometric detection (LC-MS/MS). Cereals (wheat, oats, rye, maize and rice), sunflower seeds and animal feed were spiked with sterigmatocystin at levels from 0.75 to 50 µg kg ⁻¹ to establish method performance. Using acetonitrile/water extraction followed by IAC clean-up, and analysis by HPLC with detection at 325 nm, recoveries ranged from 68% to 106%, with repeatability from 4.2% to 17.5%. The limit of quantification with UV detection in these matrices was 1.5 µg kg ⁻¹. For the analysis of beer and cheese the sample preparation prior to IAC clean-up was changed to accommodate the different properties of the matrix, prior to analysis by LC-MS/MS. For beer and cheese spiked at 5.0 µg kg ⁻¹ the recoveries were 94% and 104%, and precision (RSDs) were 1.9% and 2.9% respectively. The limits of quantification by LC-MS/MS in beer and cheese were 0.02 and 0.6 µg kg ⁻¹ respectively. The sterigmatocystin IAC was demonstrated to provide an efficient clean-up of various matrices to enable this mycotoxin to be determined by either HPLC with UV detection or LC-MS/MS.
PDF
