Aims
To assess the short- and long-term effects of postconditioning (p-cond) on infarct size, extent of myocardial salvage, and left ventricular ejection fraction (LVEF) in a series of patients ...presenting with evolving ST-elevation myocardial infarction (STEMI). Previous studies have shown that p-cond during primary percutaneous coronary intervention (PCI) confers protection against ischaemia-reperfusion injury and thus might reduce myocardial infarct size.
Methods and results
Seventy-nine patients undergoing PCI for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to p-cond (n= 39) or controls (n= 40). Postconditioning was performed by applying four consecutive cycles of 1 min balloon inflation, each followed by 1 min deflation. Infarct size, myocardial salvage, and LVEF were assessed by cardiac-MRI 1 week and 6 months after MI. Postconditioning was associated with lower myocardial salvage (4.1 ± 7.2 vs. 9.1 ± 5.8% in controls; P= 0.004) and lower myocardial salvage index (18.9 ± 27.4 vs. 30.9 ± 20.5% in controls; P= 0.038). No significant differences in infarct size and LVEF were found between the groups at 1 week and 6 months after MI.
Conclusion
This randomized study suggests that p-cond during primary PCI does not reduce infarct size or improve myocardial function recovery at both short- and long-term follow-up and might have a potential harmful effect.
The role of soil in the contribution of food and feed Silver, W L; Perez, T; Mayer, A ...
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
09/2021, Letnik:
376, Številka:
1834
Journal Article
Recenzirano
Odprti dostop
Soils play a critical role in the production of food and feed for a growing global population. Here, we review global patterns in soil characteristics, agricultural production and the fate of ...embedded soil nutrients. Nitrogen- and organic-rich soils supported the highest crop yields, yet the efficiency of nutrient utilization was concentrated in regions with lower crop productivity and lower rates of chemical fertilizer inputs. Globally, soil resources were concentrated in animal feed, resulting in large inefficiencies in nutrient utilization and losses from the food system. Intercontinental transport of soil-derived nutrients displaced millions of tonnes of nitrogen and phosphorus annually, much of which was ultimately concentrated in urban waste streams. Approximately 40% of the global agricultural land area was in small farms providing over 50% of the world's food and feed needs but yield gaps and economic constraints limit the ability to intensify production on these lands. To better use and protect soil resources in the global food system, policies and actions should encourage shifts to more nutrient-efficient diets, strategic intensification and technological improvement, restoration and maintenance of soil fertility and stability, and enhanced resilience in the face of global change. This article is part of the theme issue 'The role of soils in delivering Nature's Contributions to People'.
Signaling through retinoic acid inducible gene I (RIG-I) like receptors (RLRs) is tightly regulated, with activation occurring upon sensing of viral nucleic acids, and suppression mediated by ...negative regulators. Under homeostatic conditions aberrant activation of melanoma differentiation-associated protein-5 (MDA5) is prevented through editing of endogenous dsRNA by RNA editing enzyme Adenosine Deaminase Acting on RNA (ADAR1). In addition, ADAR1 is postulated to play pro-viral and antiviral roles during viral infections that are dependent or independent of RNA editing activity. Here, we investigated the importance of ADAR1 isoforms in modulating influenza A virus (IAV) replication and revealed the opposing roles for ADAR1 isoforms, with the nuclear p110 isoform restricting versus the cytoplasmic p150 isoform promoting IAV replication. Importantly, we demonstrate that p150 is critical for preventing sustained RIG-I signaling, as p150 deficient cells showed increased IFN-β expression and apoptosis during IAV infection, independent of RNA editing activity. Taken together, the p150 isoform of ADAR1 is important for preventing sustained RIG-I induced IFN-β expression and apoptosis during viral infection.
The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses ...can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC) as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens.
Display omitted
•Genome-wide CRISPR/Cas9 screen used to identify pro-viral IAV host factors•Host factors identified in viral entry and regulation of antiviral gene expression•Sialic acid transporter SLC35A1 is essential for viral receptor expression•Transcriptional repressor CIC is a negative regulator of cell-intrinsic immunity
Using a genome-wide CRISPR/Cas9 screen, Han et al. demonstrate that the major hit, the sialic acid transporter SLC35A1, is an essential host factor for IAV entry. In addition, they identify the DNA-binding transcriptional repressor CIC as a negative regulator of cell-intrinsic immunity.
Background
Over the month of April, Spain has become the European country with more confirmed cases of COVID-19 infection, after surpassing Italy on April 2nd. The community of Castile and León in ...Spain is one of the most affected by COVID-19 infection and the province of León has a total of 3711 cases and 425 deaths so far. Rheumatic patients should be given special attention regarding COVID-19 infection due to their immunocompromised state resulting from their underlying immune conditions and use of targeted immune-modulating therapies. Studying epidemiological and clinical characteristics of patients with rheumatic diseases infected with SARS-CoV2 is pivotal to clarify determinants of COVID-19 disease severity in patients with underlying rheumatic disease.
Objectives
To describe epidemiological characteristics of patients with rheumatic diseases hospitalized with COVID-19 and determine risk factors associated with mortality in a third level Hospital setting in León, Spain.
Methods
We performed a prospective observational study, from 1st March 2020 until the 1st of June including adults with rheumatic diseases hospitalized with COVID-19 and performed a univariate and multivariate logistic regression model to estimate ORs and 95% CIs of mortality. Age, sex, comorbidities, rheumatic disease diagnosis and treatment, disease activity prior to infection, radiographic and laboratorial results at arrival were analysed.
Results
During the study period, 3711 patients with COVID-19 were admitted to our hospital, of whom 38 (10%) had a rheumatic or musculoskeletal disease. Fifty-three percent were women, with a mean age at hospital admission of 75.3 (IQR 68–83) years. The median length of stay was 11 days. A total of 10 patients died (26%) during their hospital admission. Patients who died from COVID-19 were older (median age 78.4 IQR 74.5–83.5) than those who survived COVID-19 (median age 75.1 IQR 69.3–75.8) and more likely to have arterial hypertension (9 90% vs 14 50% patients; OR 9 (95% CI 1.0–80.8),
p
0.049), dyslipidaemia (9 (90%) vs 12 (43%); OR 12 (95% CI 1.33–108),
p
0.03), diabetes ((9 (90%) vs 6 (28%) patients; OR 33,
p
0.002), interstitial lung disease (6 (60%) vs 6 (21%); OR 5.5 (95% CI 1.16–26),
p
0.03), cardiovascular disease (8 (80%) vs 11 (39%); OR 6.18 (95% IC 1.10–34.7,
p
0.04) and a moderate/high index of rheumatic disease activity (7 (25%) vs 6(60%); OR 41.4 (4.23–405.23),
p
0.04). In univariate analyses, we also found that patients who died from COVID-19 had higher hyperinflammation markers than patients who survived: C-reactive protein (181 (IQR 120–220) vs 107.4 (IQR 30–150;
p
0.05); lactate dehydrogenase (641.8 (IQR 465.75–853.5) vs 361 (IQR 250–450),
p
0.03); serum ferritin (1026 (IQR 228.3–1536.3) vs 861.3 (IQR 389–1490.5),
p
0.04); D-dimer (12,019.8 (IQR 843.5–25,790.5) vs 1544.3 (IQR 619–1622),
p
0.04). No differences in sex, radiological abnormalities, rheumatological disease, background therapy or symptoms before admission between deceased patients and survivors were found. In the multivariate analysis, the following risk factors were associated with mortality: rheumatic disease activity (
p
= 0.003), dyslipidaemia (
p
= 0.01), cardiovascular disease (
p
= 0.02) and interstitial lung disease (
p
= 0.02). Age, hypertension and diabetes were significant predictors in univariate but not in multivariate analysis. Rheumatic disease activity was significantly associated with fever (
p
= 0.05), interstitial lung disease (
p
= 0.03), cardiovascular disease (
p
= 0.03) and dyslipidaemia (
p
= 0.01).
Conclusions
Our results suggest that comorbidities, rheumatic disease activity and laboratorial abnormalities such as C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), serum ferritin elevation significantly associated with mortality whereas previous use of rheumatic medication did not. Inflammation is closely related to severity of COVID-19.
Key Points
•
Most patients recover from COVID-19
.
•
The use of DMARDs, corticosteroids and biologic agents did not increase the odds of mortality in our study
.
•
Rheumatic disease activity might be associated with mortality
.
Background
Left atrial wall thickness (LAWT) has been related to pulmonary vein (PV) reconnections after atrial fibrillation (AF) ablation. The aim was to integrate 3D‐LAWT maps in the navigation ...system and analyze the relationship with local reconnection sites during AF‐redo procedures.
Methods
Consecutive patients referred for AF‐redo ablation were included. Procedure was performed using a single catheter technique. LAWT maps obtained from multidetector computerized tomography (MDCT) were imported into the navigation system. LAWT of the circumferential PV line, the reconnected segment and the reconnected point, were analyzed.
Results
Sixty patients 44 (73%) male, age 61 ± 10 years were included. All reconnected veins were isolated using a single catheter technique with 55 min (IQR 47–67) procedure time and 75 s (IQR 50–120) fluoroscopy time. Mean LAWT of the circumferential PV line was 1.46 ± 0.22 mm. The reconnected segment was thicker than the rest of segments of the circumferential PV line (2.05 + 0.86 vs. 1.47 + 0.76, p < .001 for the LPVs; 1.55 + 0.57 vs. 1.27 + 0.57, p < .001 for the RPVs). Mean reconnection point wall thickness (WT) was at the 82nd percentile of the circumferential line in the LPVs and at the 82nd percentile in the RPVs.
Conclusion
A single catheter technique is feasible and efficient for AF‐redo procedures. Integrating the 3D‐LAWT map into the navigation system allows a direct periprocedural estimation of the WT at any point of the LA. Reconnection points were more frequently present in thicker segments of the PV line. The use of 3D‐LAWT maps can facilitate reconnection point identification during AF‐redo ablation.
Recent field studies have shown that there are habitats in the subarctic tundra emitting N2O at exceptionally high rates. In this study, stable isotope techniques were applied to characterize the ...processes responsible for these high N2O emissions which have been found from bare peat surfaces in permafrost peatlands. The results include the first data on the nitrogen and oxygen isotopic composition of N2O emitted from arctic tundra. The emission‐weighted average δ15Nbulk value for N2O of −13.0‰ ± 2.0‰ (mean ± SD; n = 8) from the bare peat surfaces falls within the range of the emission‐weighted average values from other natural ecosystems but is distinct from those for managed/agricultural ecosystems. This implies that if in the future, a smaller rate in the overall decreasing trend of δ15Nbulk N2O tropospheric isotopic composition is found, it cannot be attributed only to agricultural N2O emission reductions from mitigation actions but also to soils in natural ecosystems that may be emitting more N2O to the atmosphere due to warmer conditions. The site preference (SP) values from emitted N2O range from −30‰ to 58‰, indicating a temporal shift of microbial production and consumption of N2O during the sampling period. Soil emission SP data suggest that the N2O emission in subarctic tundra are more likely to be produced by nitrifier denitrification in the drier study year, but due to variable published SP values for N2O production processes in soils, this interpretation has to be taken with caution. According to SP values at depth, denitrification was the main N2O production pathway. To better address the usefulness of SP in partitioning microbial mechanisms in soils, further studies in soils mesocosms are required.
Key Points
Isotopic fingerprint of N2O from permafrost peatlands in subarctic tundra is similar to that found in natural soils from other latitudes
The larger N2O emissions in subarctic tundra are more likely to be produced by nitrifier denitrification
N2O consumption is an important process in permafrost peatlands from subarctic tundra
Systematics is nowadays facing new challenges with the introduction of new concepts and new techniques. Compared to most other phyla, phylogenetic relationships among sponges are still largely ...unresolved. In the past 10 years, the classical taxonomy has been completely overturned and a review of the state of the art appears necessary. The field of taxonomy remains a prominent discipline of sponge research and studies related to sponge systematics were in greater number in the Eighth World Sponge Conference (Girona, Spain, September 2010) than in any previous world sponge conferences. To understand the state of this rapidly growing field, this chapter proposes to review studies, mainly from the past decade, in sponge taxonomy, nomenclature and phylogeny. In a first part, we analyse the reasons of the current success of this field. In a second part, we establish the current sponge systematics theoretical framework, with the use of (1) cladistics, (2) different codes of nomenclature (PhyloCode vs. Linnaean system) and (3) integrative taxonomy. Sponges are infamous for their lack of characters. However, by listing and discussing in a third part all characters available to taxonomists, we show how diverse characters are and that new ones are being used and tested, while old ones should be revisited. We then review the systematics of the four main classes of sponges (Hexactinellida, Calcispongiae, Homoscleromorpha and Demospongiae), each time focusing on current issues and case studies. We present a review of the taxonomic changes since the publication of the Systema Porifera (2002), and point to problems a sponge taxonomist is still faced with nowadays. To conclude, we make a series of proposals for the future of sponge systematics. In the light of recent studies, we establish a series of taxonomic changes that the sponge community may be ready to accept. We also propose a series of sponge new names and definitions following the PhyloCode. The issue of phantom species (potential new species revealed by molecular studies) is raised, and we show how they could be dealt with. Finally, we present a general strategy to help us succeed in building a Porifera tree along with the corresponding revised Porifera classification.
Teleost fish are in direct contact with the aquatic environment, and are therefore in continual contact with a complex and dynamic microbiota, some of which may have implications for health. Mucosal ...surfaces represent the main sites in which environmental antigens and intestinal microbiota interact with the host. Thus, the gut-associated lymphoid tissues (GALT) must develop mechanisms to discriminate between pathogenic and commensal microorganisms. Colonization of intestinal mucosal surfaces with a normal microbiota has a positive effect on immune regulatory functions of the gut, and disturbance in these immune regulatory functions by an imbalanced microbiota may contribute to the development of diseases. Significant attention has therefore been recently focused on the role of probiotics in the induction or restoration of a disturbed microbiota to its normal beneficial composition. Given this, this article explores the fascinating relationship between the fish immune system and the bacteria that are present in its intestinal microbiota, focusing on the bacterial effect on the development of certain immune responses.
Background
Esophagogastric junction outflow obstruction (EGJOO) is a newly described diagnostic entity growing in importance due to the use of high resolution manometry (HRM). There is little ...knowledge regarding its incidence, etiopathogeny, long‐term evolution, and most suitable treatment. Our objective was to increase the awareness of EGJOO to optimize the management of these patients.
Methods
We conducted a historical (retrospective and prospective) study of patients diagnosed with EGJOO using HRM combined with multichannel intraluminal impedance, comparing their manometric and impedance characteristics with those of a control group. Symptoms, etiology of obstruction, acid exposure, clinical course (and its associated factors), and response to treatment were also evaluated in the EGJOO group.
Key Results
Forty‐four subjects were included (28 patients and 16 controls). Esophagogastric junction outflow obstruction patients presented incomplete esophageal transit more frequently than controls. Patients with structural obstruction had dysphagia more frequently than patients with functional obstruction, and different manometric, impedance, and pH‐metric patterns. Over one‐third of the EGJOO patients presented a spontaneous resolution of symptoms without EGJOO treatment. In the multivariate analysis, the variables associated with this spontaneous symptomatic resolution included typical symptoms of gastro‐esophageal reflux disease or epigastralgia as the main symptom and resting or basal pressure of the upper esophageal sphincter <50 mmHg.
Conclusions & Inferences
The majority of EGJOO patients presented intact peristalsis which may compensate for the lack of EGJ relaxation. In the EGJOO patients presenting favorable factors associated with a spontaneous resolution of symptoms, invasive treatments should be considered with special caution. Structural etiologies are more amenable to management, while the remainder may improve without intervention.
Esophagogastric junction outflow obstruction is a newly described diagnosis entity, growing in importance due to the use of HRM. We study the manometric and impedance characteristics of a group of EGJOO patients (vs a control group), and their symptoms, etiology of obstruction, acid exposure, clinical course (and its associated factors), and response to treatment. We conclude that the majority of EGJOO patients present intact peristalsis which may compensate for the lack of EGJ relaxation, and that in the EGJOO patients presenting favorable factors associated with a spontaneous resolution of symptoms, invasive treatments should be considered with special caution. Both structural and non‐structural etiologies can cause EGJOO, but structural etiologies are more amenable to management, while the remainder may improve without intervention.