In the first study of leaf energy balance in tropical montane forests, we observed current leaf temperature patterns in the Atlantic forest, Brazil, and assessed whether and why patterns may vary ...among species. We found large leaf‐to‐air temperature differences that were influenced strongly by radiation and differences in leaf temperature between 2 species due to variation in leaf width and stomatal conductance. We highlight the importance of leaf functional traits for leaf thermoregulation and also note that the high radiation levels that occur in montane forests may exacerbate the threat from increasing air temperatures.
Given anticipated climate changes, it is crucial to understand controls on leaf temperatures including variation between species in diverse ecosystems. In the first study of leaf energy balance in tropical montane forests, we observed current leaf temperature patterns on 3 tree species in the Atlantic forest, Brazil, over a 10‐day period and assessed whether and why patterns may vary among species. We found large leaf‐to‐air temperature differences (maximum 18.3 °C) and high leaf temperatures (over 35 °C) despite much lower air temperatures (maximum 22 °C). Leaf‐to‐air temperature differences were influenced strongly by radiation, whereas leaf temperatures were also influenced by air temperature. Leaf energy balance modelling informed by our measurements showed that observed differences in leaf temperature between 2 species were due to variation in leaf width and stomatal conductance. The results suggest a trade‐off between water use and leaf thermoregulation; Miconia cabussu has more conservative water use compared with Alchornea triplinervia due to lower transpiration under high vapour pressure deficit, with the consequence of higher leaf temperatures under thermal stress conditions. We highlight the importance of leaf functional traits for leaf thermoregulation and also note that the high radiation levels that occur in montane forests may exacerbate the threat from increasing air temperatures.
BACKGROUND:Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes mellitus or cardiovascular disease. Lipidomics enables the assessment ...of hundreds of lipid species as potential markers for disease risk.
METHODS:Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionization–tandem mass spectrometry on a case-cohort (n=3779) subset from the ADVANCE trial (Action in Diabetes and Vascular DiseasePreterax and Diamicron-MR Controlled Evaluation). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year follow-up period. Multivariable models combining traditional risk factors with lipid species were optimized with the Akaike information criteria. C statistics and NRIs were calculated within a 5-fold cross-validation framework.
RESULTS:Sphingolipids, phospholipids (including lyso- and ether- species), cholesteryl esters, and glycerolipids were associated with future cardiovascular events and cardiovascular death. The addition of 7 lipid species to a base model (14 traditional risk factors and medications) to predict cardiovascular events increased the C statistic from 0.680 (95% confidence interval CI, 0.678–0.682) to 0.700 (95% CI, 0.698–0.702; P<0.0001) with a corresponding continuous NRI of 0.227 (95% CI, 0.219–0.235). The prediction of cardiovascular death was improved with the incorporation of 4 lipid species into the base model, showing an increase in the C statistic from 0.740 (95% CI, 0.738–0.742) to 0.760 (95% CI, 0.757–0.762; P<0.0001) and a continuous net reclassification index of 0.328 (95% CI, 0.317–0.339). The results were validated in a subcohort with type 2 diabetes mellitus (n=511) from the LIPID trial (Long-Term Intervention With Pravastatin in Ischemic Disease).
CONCLUSIONS:The improvement in the prediction of cardiovascular events, above traditional risk factors, demonstrates the potential of plasma lipid species as biomarkers for cardiovascular risk stratification in diabetes mellitus.
CLINICAL TRIAL REGISTRATION:URLhttps://clinicaltrials.gov. Unique identifierNCT00145925.
The authors sought to evaluate the plaque-modifying effects of low-dose colchicine therapy plus optimal medical therapy (OMT) in patients post-acute coronary syndrome (ACS), as assessed by coronary ...computed tomography angiography (coronary CTA).
Colchicine therapy has been postulated to have beneficial anti-inflammatory effects in patients with ACS, translating into reduction in future adverse cardiovascular events. However, whether favorable plaque modification underpins this is yet unproven.
In this prospective nonrandomized observational study of 80 patients with recent ACS (<1 month), patients received either 0.5 mg/day colchicine plus OMT or OMT alone and were followed for 1 year. Our primary outcome was change in low attenuation plaque volume (LAPV), a marker of plaque instability on coronary CTA and robust predictor of adverse cardiovascular events. Secondary outcomes were changes in other coronary CTA measures and in high-sensitivity C-reactive protein (hsCRP).
Mean duration of follow-up was 12.6 months; mean age was 57.4 years. Colchicine therapy significantly reduced LAPV (mean 15.9 mm
-40.9% vs. 6.6 mm
-17.0%; p = 0.008) and hsCRP (mean 1.10 mg/l -37.3% vs. 0.38 mg/l -14.6%; p < 0.001) versus controls. Reductions in total atheroma volume (mean 42.3 mm
vs. 26.4 mm
; p = 0.28) and low-density lipoprotein levels (mean 0.44 mmol/l vs. 0.49 mmol/l; p = 0.21) were comparable in both groups. With multivariate linear regression, colchicine therapy remained significantly associated with greater reduction in LAPV (p = 0.039) and hsCRP (p = 0.004). There was also a significant linear association (p < 0.001) and strong positive correlation (r = 0.578) between change in LAPV and hsCRP.
Our findings suggest, for the first time, that low-dose colchicine therapy favorably modifies coronary plaque, independent of high-dose statin intensification therapy and substantial low-density lipoprotein reduction. The improvements in plaque morphology are likely driven by the anti-inflammatory properties of colchicine, as demonstrated by reductions in hsCRP, rather than changes in lipoproteins. Colchicine may be beneficial as an additional secondary prevention agent in patients post-ACS if validated in future studies.
Intestinal barrier function is reduced in inflammatory bowel disease (IBD). Tumor necrosis factor (TNF) and interleukin (IL)-13, which are up-regulated in IBD, induce barrier defects that are ...associated with myosin light chain kinase (MLCK) activation and increased claudin-2 expression, respectively, in cultured intestinal epithelial monolayers. Here we report that these independent signaling pathways have distinct effects on tight junction barrier properties and interact in vivo. MLCK activation alters size selectivity to enhance paracellular flux of uncharged macromolecules without affecting charge selectivity and can be rapidly reversed by MLCK inhibition. In contrast, IL-13-dependent claudin-2 expression increases paracellular cation flux in vitro and in vivo without altering tight junction size selectivity but is unaffected by MLCK inhibition in vitro. In vivo, MLCK activation increases paracellular flux of uncharged macromolecules and also triggers IL-13 expression, claudin-2 synthesis, and increased paracellular cation flux. We conclude that reversible, MLCK-dependent permeability increases cause mucosal immune activation that, in turn, feeds back on the tight junction to establish long-lasting barrier defects. Interactions between these otherwise distinct tight junction regulatory pathways may contribute to IBD pathogenesis.
The platinum chemotherapy agents cisplatin and carboplatin are widely used in the treatment of adult and pediatric cancers. Cisplatin causes hearing loss in at least 60% of pediatric patients. ...Reducing cisplatin and high-dose carboplatin ototoxicity without reducing efficacy is important.
This review summarizes recommendations made at the 42nd Congress of the International Society of Pediatric Oncology (SIOP) in Boston, October 21-24, 2010, reflecting input from international basic scientists, pediatric oncologists, otolaryngologists, oncology nurses, audiologists, and neurosurgeons to develop and advance research and clinical trials for otoprotection.
Platinum initially impairs hearing in the high frequencies and progresses to lower frequencies with increasing cumulative dose. Genes involved in drug transport, metabolism, and DNA repair regulate platinum toxicities. Otoprotection can be achieved by acting on several these pathways and generally involves antioxidant thiol agents. Otoprotection is a strategy being explored to decrease hearing loss while maintaining dose intensity or allowing dose escalation, but it has the potential to interfere with tumoricidal effects. Route of administration and optimal timing relative to platinum therapy are critical issues. In addition, international standards for grading and comparing ototoxicity are essential to the success of prospective pediatric trials aimed at reducing platinum-induced hearing loss.
Collaborative prospective basic and clinical trial research is needed to reduce the incidence of irreversible platinum-induced hearing loss, and optimize cancer control. Wide use of the new internationally agreed-on SIOP Boston ototoxicity scale in current and future otoprotection trials should help facilitate this goal.
Low density lipoprotein (LDL) is the predominant atherogenic lipoprotein particle in the circulation. Conventionally, a fasting lipid profile has been used for atherosclerotic cardiovascular disease ...(ASCVD) risk assessment. A non-fasting sample is now regarded as a suitable alternative to a fasting sample. In routine clinical practice, the Friedewald equation is used to estimate LDL-cholesterol, but it has limitations. Commercially available direct measures of LDL-cholesterol are not standardised. LDL-cholesterol is a well-established risk factor for ASCVD, being the primary therapeutic target in both primary and secondary prevention. Non-high-density lipoprotein (HDL)-cholesterol is a measure of the cholesterol content in the atherogenic lipoproteins, but it does not reflect the particle number. Non-HDL-cholesterol has the advantage over LDL-cholesterol of including remnant cholesterol and being independent of triglyceride variability, but it is compromised by the non-specificity bias of direct HDL-cholesterol methods used in the calculation. Apolipoprotein (apo) B, the major structural protein in very low-density lipoprotein, intermediate density lipoprotein, LDL and lipoprotein (a), is a measure of the number of atherogenic lipoproteins. ApoB methods are standardised, but the assay comes at an additional, albeit relatively low cost. Non-HDL-cholesterol and apoB are more accurate measures than LDL-cholesterol in hypertriglyceridaemic individuals, non-fasting samples, and in those with very-low LDL-cholesterol concentrations. Accumulating evidence suggests that non-HDL-cholesterol and apoB are superior to LDL-cholesterol in predicting ASCVD risk, and both have been designated as secondary targets in some treatment guidelines. We review the measurement, potential role, utility and current status of non-HDL-cholesterol and apoB when compared with LDL-cholesterol in ASCVD risk assessment.
The widespread use of pharmaceuticals by human populations results in their sustained discharge to surface waters via wastewater treatment plants (WWTPs). In this study, 16 highly prescribed ...pharmaceuticals were quantified along a 250 km transect of the Hudson River Estuary and New York Harbor to describe their sources and spatial patterns. Sampling was conducted over two dry weather periods in May and July 2016, at 72 sites which included mid-channel and nearshore sites, as well as locations influenced by tributaries and WWTP outfalls. The detection frequency of the study pharmaceuticals was almost identical between the May and July sampling periods at 55% and 52%, respectively. Six pharmaceuticals were measurable at 92% or more of the sites during both sampling periods, illustrating their ubiquitous presence throughout the study area. Individual pharmaceutical concentrations were highly variable spatially, ranging from non-detect to 3810 ng/L during the study. Major factors controlling concentrations were proximity and magnitude of WWTP discharges, inputs from tributaries and tidal mixing. Two compounds, sucralose and caffeine, were evaluated as tracers to identify wastewater sources and assess pharmaceutical behavior. Sucralose was useful in identifying wastewater inputs to the river and concentrations showed excellent correlations with numerous pharmaceuticals in the study. Caffeine-sucralose ratios showed potential in identifying discharges of untreated wastewater occurring during a combined sewage overflow event. Many of the study pharmaceuticals were present throughout the Hudson River Estuary as a consequence of sustained wastewater discharge. Whereas some concentrations were above published effects levels, a more complete risk assessment is needed to understand the potential for ecological impacts due to pharmaceuticals in the Hudson River Estuary.
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•High resolution sampling shows the spatial distribution of pharmaceuticals.•Tracers were successful in identifying and differentiating wastewater sources.•Sucralose proved effective as a tracer for select pharmaceutical compounds.•Wastewater discharges produce sustained, elevated levels of pharmaceuticals.
Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of ...epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.
Abstract
Aims
Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD ...risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies.
Methods and results
Ceramides and PCs were analysed using liquid chromatography–mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28–1.63) in WECAC, 1.47 (1.34–1.61) in the LIPID trial, and 1.69 (1.31–2.17) in KAROLA. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44–1.85) and 2.04 (1.57–2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention.
Conclusion
A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.
With the development of reliable endoscopic closure techniques and tools, endoscopic full-thickness resection (EFTR) is emerging as a therapeutic option for the treatment of subepithelial tumors and ...epithelial neoplasia with significant fibrosis. EFTR may be categorized as “exposed” and “nonexposed.” In exposed EFTR, the full-thickness resection is undertaken with a tunneled or nontunneled technique, with subsequent closure of the defect. In nonexposed EFTR, a secure serosa-to-serosa apposition is achieved before full-thickness resection of the isolated lesion. This document reviews current techniques and devices used for EFTR and reviews clinical applications and outcomes.
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