Idiopathic pulmonary fibrosis (IPF) is a restrictive lung disease that is associated with high morbidity and mortality. Current medical therapies are not fully effective at limiting mortality in ...patients with IPF, and new therapies are urgently needed. Matrix metalloproteinases (MMPs) are proteinases that, together, can degrade all components of the extracellular matrix and numerous nonmatrix proteins. MMPs and their inhibitors, tissue inhibitors of MMPs (TIMPs), have been implicated in the pathogenesis of IPF based upon the results of clinical studies reporting elevated levels of MMPs (including MMP-1, MMP-7, MMP-8, and MMP-9) in IPF blood and/or lung samples. Surprisingly, studies of gene-targeted mice in murine models of pulmonary fibrosis (PF) have demonstrated that most MMPs promote (rather than inhibit) the development of PF and have identified diverse mechanisms involved. These mechanisms include MMPs: (1) promoting epithelial-to-mesenchymal transition (MMP-3 and MMP-7); (2) increasing lung levels or activity of profibrotic mediators or reducing lung levels of antifibrotic mediators (MMP-3, MMP-7, and MMP-8); (3) promoting abnormal epithelial cell migration and other aberrant repair processes (MMP-3 and MMP-9); (4) inducing the switching of lung macrophage phenotypes from M1 to M2 types (MMP-10 and MMP-28); and (5) promoting fibrocyte migration (MMP-8). Two MMPs, MMP-13 and MMP-19, have antifibrotic activities in murine models of PF, and two MMPs, MMP-1 and MMP-10, have the potential to limit fibrotic responses to injury. Herein, we review what is known about the contributions of MMPs and TIMPs to the pathogenesis of IPF and discuss their potential as therapeutic targets for IPF.
Particle size-selective sampling refers to the collection of particles of varying sizes that potentially reach and adversely affect specific regions of the respiratory tract. Thoracic and respirable ...fractions are defined as the fraction of inhaled particles capable of passing beyond the larynx and ciliated airways, respectively, during inhalation. In an attempt to afford greater protection to exposed individuals, current size-selective sampling criteria overestimate the population means of particle penetration into regions of the lower respiratory tract. The purpose of our analyses was to provide estimates of the thoracic and respirable fractions for adults and children during typical activities with both nasal and oral inhalation, that may be used in the design of experimental studies and interpretation of health effects evidence.
We estimated the fraction of inhaled particles (0.5-20 μm aerodynamic diameter) penetrating beyond the larynx (based on experimental data) and ciliated airways (based on a mathematical model) for an adult male, adult female, and a 10 yr old child during typical daily activities and breathing patterns.
Our estimates show less penetration of coarse particulate matter into the thoracic and gas exchange regions of the respiratory tract than current size-selective criteria. Of the parameters we evaluated, particle penetration into the lower respiratory tract was most dependent on route of breathing. For typical activity levels and breathing habits, we estimated a 50% cut-size for the thoracic fraction at an aerodynamic diameter of around 3 μm in adults and 5 μm in children, whereas current ambient and occupational criteria suggest a 50% cut-size of 10 μm.
By design, current size-selective sample criteria overestimate the mass of particles generally expected to penetrate into the lower respiratory tract to provide protection for individuals who may breathe orally. We provide estimates of thoracic and respirable fractions for a variety of breathing habits and activities that may benefit the design of experimental studies and interpretation of particle size-specific health effects.
Due to the widespread use of the pour-through extraction procedure in horticultural production and research, the objective of this study was to determine if the method is biased by preferentially ...extracting substrate solution near the bottom of the container in both conventionally filled containers as well as intentionally stratified containers. Eight treatments were created using 2.5-L, 17.5-cm tall plastic nursery containers. The first four treatments were created by layering a conventional pine bark substrate (CONV) that was either amended (+A) or nonamended (−A) with fertilizer and lime with the following layers: amended substrate throughout the entire container profile (+A/+A); amended substrate in the top half (top 8.5 cm) over nonamended substrate in the bottom half of the container profile (+A/−A); nonamended substrate in the top half over amended substrate in the bottom half (−A/+A); and nonamended substrate throughout the profile (−A/−A). An additional four treatments were created by intentionally stratifying (STRAT) a fine pine bark substrate (FINE) over a coarse pine bark substrate (CRSE) with the same amendment combinations of +A or −A. On 0 and 42 d after potting, substrate pH and electrical conductivity (EC) were determined on samples collected by the pour-through procedure and 1:1 water extracts of the top and bottom layers in the container. At 42 d after potting, nutrient ions (NO 3 − , PO 4 2− , K, Ca, Mg, and SO 4 2− ) were also measured in both pour-through and 1:1 water extracts of the top and bottom layers. At both dates and in both CONV and STRAT containers, pour-through substrate pH and EC more closely reflected those measurements in the bottom half of the container as determined by the 1:1 water extract. At 42 d after potting, nutrient ions determined by the pour-through procedure were more highly correlated to the 1:1 water extracts from the bottom half of the container compared with the top half of the container in both CONV and STRAT substrates. Evidence herein demonstrates that the pour-through procedure is more reflective of the lower half of the container than the upper half for both CONV and stratified substrates.
This study investigates the potential benefits of using tectonite dust as a soil amendment in central Oregon. Tectonite, a rare mineral byproduct of the Warm Springs Composite Products Company, has ...unique properties that can enhance soil fertility and water-holding capacity. The study includes analyses of tectonite's physical and chemical properties, small-scale growth trials, and farm-scale experiments to measure grain yield. Physical property analysis demonstrated that tectonite increased water-holding capacity and improved soil structure when added to bark substrates. Responses varied in mineral soils, affecting air space, and water-holding capacity. Small-scale trials showed positive growth responses in wheat height and biomass, indicating improved early growth and establishment. Farm-scale experiments confirmed increased grain yields with tectonite application. These findings suggest that tectonite enhances soil health and crop yields by improving structure, nutrient availability, and water retention. Careful sourcing and testing are necessary to address potential heavy metal contamination risks. Using tectonite as a soil amendment aligns with sustainability goals, reducing waste, and greenhouse gas emissions. It may also offer cost savings compared to synthetic fertilizers and stimulate the local economy. Further research is needed to understand the long-term effects of tectonite on edible crops and heavy metal content. Nevertheless, tectonite shows promise as a sustainable soil amendment for promoting agriculture in central Oregon. By exploring its potential benefits, farmers can enhance soil fertility, improve water-use efficiency, and contribute to a more sustainable agricultural system. This study highlights the importance of utilizing waste byproducts in agriculture to achieve environmental and economic sustainability. Tectonite has the potential to play a significant role in addressing water scarcity and enhancing crop productivity in arid regions like central Oregon.
Summary
Modern thrombophilia testing fails to identify any underlying prothrombotic tendency in a significant number of patients presenting with objectively confirmed venous thromboemboembolism ...(VTE). This observation has led to a search for other novel inherited or acquired human thrombophilias. Although a number of putative mechanisms have been described, the evidence behind many of these candidates remains weak. In contrast, an increasing body of work supports the hypothesis that increased plasma factor VIII (FVIII) levels may be important in this context. An association between elevated plasma FVIII levels and VTE was first described in the Leiden Thrombophilia Study (LETS). Subsequently, these conclusions have been supported by an increasing number of independent case–control studies. Cumulatively, these studies have clearly demonstrated that high FVIII levels constitute a prevalent, dose‐dependent risk factor for VTE. Furthermore, more recent studies have shown that the risk of recurrent venous thrombosis is also significantly increased in patients with high FVIII levels. In this review, we present the evidence supporting the hypothesis that elevated FVIII levels constitute a clinically important thrombophilia. In addition, we examine the biological mechanisms that may underlie persistently elevated FVIII levels, and the pathways through which high FVIII may serve to increase thrombotic risk.
Floating treatment wetlands (FTWs) are a relatively new water treatment practice that consists of emergent wetland plants planted on floating mats constructed of buoyant material. This study utilized ...batch-fed mesocosms, with a seven-day retention time, to investigate the total nitrogen (TN) and phosphorus (TP) remediation capability of two commercially available FTW technologies using runoff from a combined irrigation holding and stormwater retention pond. Nutrients in the pond water are attributed to runoff from nearby fertilized research plots upgradient. The FTW technologies included Beemats (Beemats LLC, New Smyrna Beach, FL, USA) and BioHaven® floating islands (Floating Island International, Inc. Shepard, MT, USA) planted with Juncus effusus (soft rush). Due to an increase in TN and TP in the initial phase of the experiment during the plant establishment phase (weeks 1–8), BioHaven®nutrient removal was lower over the entire experimental period than the Beemat treatment. Differences between the two treatments, such as mat material or substrate materials and/or additives may account for this difference. The BioHaven® FTW removed 25% and 4%, while the Beemat removed 40% and 48% of the TN and TP, respectively expressed in terms of net removal over the entire study. During the plant growth season (weeks 9–18 of the study), the two technologies showed similar nutrient removal rates: for TN:0.026±0.0032 and 0.025±0.0018, and for TP:0.0074±0.00049 and 0.0076±0.00065g/m2/day for Beemat and Biohaven®, respectively. A control treatment, meant to reflect nutrient removal within the pond without the presence of plants, yielded 28% and 31% removal of TN and TP, respectively. Thus, the Beemat mat yielded a significant positive net removal of TN and TP. The BioHaven® biomass was significantly greater than the Beemat treatment. Both treatments showed greater biomass accumulation in shoots rather than in roots. Plant nutrient content was similar between the two treatments.
Summary Background International research for acute myocardial infarction lacks comparisons of whole health systems. We assessed time trends for care and outcomes in Sweden and the UK. Methods We ...used data from national registries on consecutive patients registered between 2004 and 2010 in all hospitals providing care for acute coronary syndrome in Sweden and the UK. The primary outcome was all-cause mortality 30 days after admission. We compared effectiveness of treatment by indirect casemix standardisation. This study is registered with ClinicalTrials.gov , number NCT01359033. Findings We assessed data for 119 786 patients in Sweden and 391 077 in the UK. 30-day mortality was 7·6% (95% CI 7·4–7·7) in Sweden and 10·5% (10·4–10·6) in the UK. Mortality was higher in the UK in clinically relevant subgroups defined by troponin concentration, ST-segment elevation, age, sex, heart rate, systolic blood pressure, diabetes mellitus status, and smoking status. In Sweden, compared with the UK, there was earlier and more extensive uptake of primary percutaneous coronary intervention (59% vs 22%) and more frequent use of β blockers at discharge (89% vs 78%). After casemix standardisation the 30-day mortality ratio for UK versus Sweden was 1·37 (95% CI 1·30–1·45), which corresponds to 11 263 (95% CI 9620–12 827) excess deaths, but did decline over time (from 1·47, 95% CI 1·38–1·58 in 2004 to 1·20, 1·12–1·29 in 2010; p=0·01). Interpretation We found clinically important differences between countries in acute myocardial infarction care and outcomes. International comparisons research might help to improve health systems and prevent deaths. Funding Seventh Framework Programme for Research, National Institute for Health Research, Wellcome Trust (UK), Swedish Association of Local Authorities and Regions, Swedish Heart-Lung Foundation.
•We evaluated FTWs for use in treating runoff from commercial nurseries.•High and low nutrient concentrations were assessed in replicated mesocosms.•FTW plants included Pontederia cordata and Juncus ...effusus, grown in Beemat rafts.•Pontederia removed over 90% of total phosphorus and over 84% of total nitrogen.•Pontederia performed significantly better than Juncus.
Floating treatment wetlands (FTWs) are an emerging surface water treatment practice for reducing nutrients such as nitrogen (N) and phosphorus (P) in a variety of waste streams. FTWs consist of floating rafts which support wetland plants allowing the plant roots to be submerged below the water surface similar to hydroponic systems. N and P removal is achieved through direct plant uptake and flocculation or sedimentation facilitated by biofilms adhering to plant roots. While research has documented FTW performance for a variety of waste streams, little information is available on runoff from commercial nurseries. Nursery runoff occurs frequently, from storm and irrigation events, and can potentially contain elevated concentrations of total N (TN) and total P (TP) due to crop fertilization and frequent irrigation. Nursery runoff is often captured in large ponds known as tailwater recovery basins (TRBs) for reuse. We assessed the effectiveness of FTWs for treating nursery runoff in TRBs over a 7-day hydraulic retention time across a 19-week growing season using two supplied nutrient concentrations and four treatments with four replicates in a randomized complete block mesocosm experiment. The high nutrient concentration averaged 17.1 mg·L−1 TN and 2.61 mg·L−1 TP and low nutrient concentration averaged 5.22 mg·L−1 TN and 0.52 mg·L−1 TP. Treatments included: 1) Pontederia cordata, 2) Juncus effusus, 3) a raft with no plants, and 4) no raft (open-water). Pontederia cordata removed 90% and 92% of TP and 84% and 89% TN, depending on initial loading; performing better than the other planted and non-planted treatments. Juncus effusus performed better than the mat-only control treatments for TP and TN removal across nutrient concentrations tested, but performed similarly to the open water control when nutrient load was evaluated. Nutrient uptake by Pontederia cordata averaged 0.026 g·m−2·d−1 N and 0.0075 g·m−2·d−1 P. The study demonstrated that FTWs can be very effective, but nutrient removal depends greatly upon plant species selection.
Highlights • Markers of inflammation and oxidative stress were higher in MDD. • SSRI treatment response was associated with oxidative stress and inflammation. • Medications, somatic conditions or ...health behaviors did not affect the findings.
Urbanization increases runoff, sediment, and nutrient loadings downstream, causing flooding, eutrophication, and harmful algal blooms. Stormwater control measures (SCMs) are used to address these ...concerns and are designed based on inflow loads. Thus, estimating nutrient and sediment loads is important for meeting restoration objectives. Pollutants accumulate on surfaces during dry periods, making Event Mean Concentration (EMC) a function of antecedent dry period (ADP). An EMC results from wash-off of accumulated pollutants from catchment surface during runoff events. However, several studies found little to no correlation between constituent concentrations in stormwater and ADP. The objective of this study is to verify this finding and discover which climatological or catchment characteristics most significantly affect stormwater quality. Stormwater quality data were obtained from the National Stormwater Quality Database (NSQD), which is the largest data repository of stormwater quality data in the U.S. Bayesian Network Structure Learner (BNSL) was used to assess the relationships between catchment characteristics, climatological information, and stormwater quality for selected land uses. Given the optimal BN structure, it was determined which parameters most affect stormwater quality EMCs. The results demonstrate that both catchment and rain characteristics affected stormwater quality EMCs. Among catchment characteristics, land use (LU) was the most important factor and catchment size was the least. Precipitation depth (P) and duration (D) affected Total Phosphorus (TP), Total Nitrogen (TN), and Total Suspended Solids (TSS). This indicated that it is likely that P and D had a greater influence on stormwater quality more than ADP. P, D, and ADP affected the dissolved constituents of TN (i.e. NO2-N/NO3-N) and TP (i.e. Ortho-P). Compared to other factors (i.e. P and D), the effect of ADP on TSS was negligible. Stormwater quality EMCs related to nitrogen were not affected by catchment slope (S). However, TSS and Ortho-P were influenced by S.
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•Bayesian network structure learner was used to assess EMCs across the U.S.•Similar studies have been limited to LU and/or antecedent dry period (ADP).•Precipitation depth and duration exert a greater influence on EMCs than ADP.•ADP affected dissolved constituents of total nitrogen (TN) and phosphorus (TP).•Potential sources of variability in nutrients and sediment EMCs were identified.
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