The BLISTER Score: A Novel, Externally Validated Tool for Predicting Cardiac Implantable Electronic Device Infections, and Its Cost-Utility Implications for Antimicrobial Envelope Use.

BACKGROUND: Antimicrobial envelopes reduce the incidence of cardiac implantable electronic device infections, but their cost restricts routine use in the United Kingdom. Risk scoring could help to identify which patients would most benefit from this technology. METHODS: A novel risk score (BLISTER [Blood results, Long procedure time, Immunosuppressed, Sixty years old (or younger), Type of procedure, Early re-intervention, Repeat procedure]) was derived from multivariate analysis of factors associated with cardiac implantable electronic device infection. Diagnostic utility was assessed against the existing PADIT score (Prior procedure, Age, Depressed renal function, Immunocompromised, Type of procedure) in both standard and high-risk external validation cohorts, and cost-utility models examined different BLISTER and PADIT score thresholds for TYRX (Medtronic; Minneapolis, MN) antimicrobial envelope allocation. RESULTS: In a derivation cohort (n=7383), cardiac implantable electronic device infection occurred in 59 individuals within 12 months of a procedure (event rate, 0.8%). In addition to the PADIT score constituents, lead extraction (hazard ratio, 3.3 [95% CI, 1.9-6.1]; P<0.0001), C-reactive protein >50 mg/L (hazard ratio, 3.0 [95% CI, 1.4-6.4]; P=0.005), reintervention within 2 years (hazard ratio, 10.1 [95% CI, 5.6-17.9]; P<0.0001), and top-quartile procedure duration (hazard ratio, 2.6 [95% CI, 1.6-4.1]; P=0.001) were independent predictors of infection. The BLISTER score demonstrated superior discriminative performance versus PADIT in the standard risk (n=2854, event rate: 0.8%, area under the curve, 0.82 versus 0.71; P=0.001) and high-risk validation cohorts (n=1961, event rate: 2.0%, area under the curve, 0.77 versus 0.69; P=0.001), and in all patients (n=12 198, event rate: 1%, area under the curve, 0.8 versus 0.75, P=0.002). In decision-analytic modeling, the optimum scenario assigned antimicrobial envelopes to patients with BLISTER scores ≥6 (10.8%), delivering a significant reduction in infections (relative risk reduction, 30%; P=0.036) within the National Institute for Health and Care Excellence cost-utility thresholds (incremental cost-effectiveness ratio, £18 446). CONCLUSIONS: The BLISTER score (https://qxmd.com/calculate/calculator_876/the-blister-score-for-cied-infection) was a valid predictor of cardiac implantable electronic device infection, and could facilitate cost-effective antimicrobial envelope allocation to high-risk patients.

DOACs vs Vitamin K Antagonists During Cardiac Rhythm Device Surgery: A Multicenter Propensity-Matched Study.

BACKGROUND: There is a paucity of data comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) at the time of cardiac implantable electronic device (CIED) surgery. Furthermore, the best management of DOACs (interruption vs continuation) is yet to be determined. OBJECTIVES: This study aimed to compare the incidence of device-related bleeds and thrombotic events based on anticoagulant type (DOAC vs VKA) and regimen (interrupted vs uninterrupted). METHODS: This was an observational multicenter study. We included patients on chronic oral anticoagulation undergoing CIED surgery. Patients were matched using propensity scoring. RESULTS: We included 1,975 patients (age 73.8 ± 12.4 years). Among 1,326 patients on DOAC, this was interrupted presurgery in 78.2% (n = 1,039) and continued in 21.8% (n = 287). There were 649 patients on continued VKA. The matched population included 861 patients. The rate of any major bleeding was higher with continued DOAC (5.2%) compared to interrupted DOAC (1.7%) and continued VKA (2.1%) (P = 0.03). The rate of perioperative thromboembolism was 1.4% with interrupted DOAC, whereas no thromboembolic events occurred with DOAC or VKA continuation (P = 0.04). The use of dual antiplatelet therapy, DOAC continuation, and male sex were independent predictors of major bleeding on a multivariable analysis. CONCLUSIONS: In this large real-world cohort, a continued DOAC strategy was associated with a higher bleeding risk compared to DOAC interruption or VKA continuation in patients undergoing CIED surgery. However, DOAC interruption was associated with increased thromboembolic risk. Concomitant dual antiplatelet therapy should be avoided whenever clinically possible. A bespoke approach is necessary, with a strategy of minimal DOAC interruption likely to represent the best compromise.

Detecting deceased patients on cardiac device remote monitoring: A case series and management guide for cardiac device services.

BACKGROUND: Remote monitoring (RM) of implantable cardiac devices provides substantial and complex information, presenting new challenges such as detection of a patient's death. OBJECTIVE: This study aims to describe RM transmissions indicating death and propose a management strategy for services. METHODS: The study included consecutive ambulatory outpatients whose deaths were detected via RM. Clinical and device data were collected from electronic records, and ethical approval was obtained from the service's institutional review board. RESULTS: Over a 9-year period (2014-2023), 28 patients were detected. The deceased patients had implantable cardioverter-defibrillators, pacemakers, and implantable loop recorders. In 54% of the cases, the patient's death had already been recognized. Alert transmissions indicating death were commonly related to ventricular arrhythmia events, but also due to lead measurements, and implantable loop recorder battery status. Several diagnostic features may indicate a patient's death. The most reliable was the presenting electrogram, demonstrating base rate pacing with no capture. Device diagnostics, lead parameters, and arrhythmia recordings may indicate death; however, not all cases present with recordings and diagnosis may not be conclusive. A majority (82%) had ventricular arrhythmia at the time of death. In cases where defibrillator shocks were delivered, the arrhythmia reinitiated shortly after successful cardioversion. Delayed therapy was observed, and some patients did not receive defibrillator shocks because of discriminators or because the arrhythmia rate fell below the shock zone. CONCLUSION: Detecting a patient death via RM presents unique challenges and considerations for services. Standard operational policies and legal consultation should be established to address the implications.

Long-term impacts of conservation pasture management in manuresheds on system-level microbiome and antibiotic resistance genes.

Animal manure improves soil fertility and organic carbon, but long-term deposition may contribute to antibiotic resistance genes (ARGs) entering the soil-water environment. Additionally, long-term impacts of applying animal manure to soil on the soil-water microbiome, a crucial factor in soil health and fertility, are not well understood. The aim of this study is to assess: (1) impacts of long-term conservation practices on the distribution of ARGs and microbial dynamics in soil, and runoff; and (2) associations between bacterial taxa, heavy metals, soil health indicators, and ARGs in manures, soils, and surface runoff in a study following 15 years of continuous management. This management strategy consists of two conventional and three conservation systems, all receiving annual poultry litter. High throughput sequencing of the 16S ribosomal RNA was carried out on samples of cattle manure, poultry litter, soil, and runoff collected from each manureshed. In addition, four representative ARGs (intl1, sul1, ermB, and blactx-m-32) were quantified from manures, soil, and runoff using quantitative PCR. Results revealed that conventional practice increased soil ARGs, and microbial diversity compared to conservation systems. Further, ARGs were strongly correlated with each other in cattle manure and soil, but not in runoff. After 15-years of conservation practices, relationships existed between heavy metals and ARGs. In the soil, Cu, Fe and Mn were positively linked to intl1, sul1, and ermB, but trends varied in runoff. These findings were further supported by network analyses that indicated complex co-occurrence patterns between bacteria taxa, ARGs, and physicochemical parameters. Overall, this study provides system-level linkages of microbial communities, ARGs, and physicochemical conditions based on long-term conservation practices at the soil-water-animal nexus.

The Effects of Implicit Theories on Body Weight Information Avoidance.

Regular self-weighing is associated with more effective weight control, yet many individuals avoid weight-related information. Implicit theories about weight, or perceptions of how malleable weight is, predict more effortful weight management and may also influence weight-related information avoidance. Participants (N = 209) were randomly assigned to read an article stressing an incremental theory of weight (i.e., weight is malleable), an article stressing an entity theory (i.e., weight is fixed), or to a control condition. We then examined their self-reported preference to avoid their body composition (i.e., body fat, weight, and muscle composition), their willingness to have their body composition measured during the lab visit, and their eating and exercise intentions. There were no notable differences across conditions, but higher self-reported incremental beliefs predicted less self-reported avoidance of body composition. The findings suggest that implicit theories may influence weight-related information avoidance, but a brief manipulation is not powerful enough to create meaningful change.

Using artificial intelligence to identify the top 50 independent predictors of subjective well-being in a multinational sample of 37,991 older European & Israeli adults.

Subjective well-being (SWB) is widely recognized as an important health outcome, but its complexity, myriad predictors, and analytic requirements pose significant challenges to identifying the relative order and impact of SWB determinants. This study involved a representative sample of 37,991 older adults from 17 European countries and Israel. An aggregate index of SWB was developed and compared across countries, and machine-learning algorithms were used to rank-order the strongest 50 (of an initial 94) SWB predictors from 15 categories. General Additive Modeling (GAM) and low-degree polynomials (i.e., splines) were used to determine the independent effect sizes and significance levels for each of these top-50 SWB predictors. Of the 18 countries included in this study, Denmark had the highest mean SWB, while Greece had the lowest. The two top-ranked SWB predictors (loneliness, social activity satisfaction) were social factors, which also had the highest overall group ranking, followed by physical health, demographics, financial status and personality. Self-reported health was the strongest health-related predictor, neuroticism was the strongest personality predictor, and women reported higher SWB than men. SWB decreased with age, and increased with income up to 350,000 euros/year, after which it declined. Social factors were of primary importance for subjective well-being in this research, while childhood experiences and healthcare status exerted the smallest effects. The vast majority of the top 50 SWB predictors were statistically significant, with the notable exceptions of body mass index and most health behaviors, which may impact SWB indirectly through their effects on physical health. Future multivariate modeling is recommended to clarify the mechanisms for these and other observed relationships.

Improved delivery of rate-adaptive pacing using an impedance-derived contractility sensor in high-intensity exercise: A case report.

Effective rate-adaptive pacing may be difficult in the presence of atrial fibrillation (AF), and is important during high-intensity exercise. This case presents a 74-year-old elite cyclist with AF and a biventricular pacemaker after atrioventricular (AV) node ablation. He reported sudden breathlessness due to heart rate drops, caused by breaching the artefact threshold on the minute-ventilation sensor. He was exchanged to a generator with an impedance-derived contractility sensor (closed-loop stimulation), resulting in resolution of symptoms, and no further rate drops. This is the first description of the utility of closed-loop stimulation in high-intensity exercise.

Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial.

AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.

Hierarchical Pooling in Graph Neural Networks to Enhance Classification Performance in Large Datasets.

Deep learning methods predicated on convolutional neural networks and graph neural networks have enabled significant improvement in node classification and prediction when applied to graph representation with learning node embedding to effectively represent the hierarchical properties of graphs. An interesting approach (DiffPool) utilises a differentiable graph pooling technique which learns 'differentiable soft cluster assignment' for nodes at each layer of a deep graph neural network with nodes mapped on sets of clusters. However, effective control of the learning process is difficult given the inherent complexity in an 'end-to-end' model with the potential for a large number parameters (including the potential for redundant parameters). In this paper, we propose an approach termed FPool, which is a development of the basic method adopted in DiffPool (where pooling is applied directly to node representations). Techniques designed to enhance data classification have been created and evaluated using a number of popular and publicly available sensor datasets. Experimental results for FPool demonstrate improved classification and prediction performance when compared to alternative methods considered. Moreover, FPool shows a significant reduction in the training time over the basic DiffPool framework.

Hydrogen Sulfide and the Immune System.

Hydrogen sulfide (H2S) is the "third gasotransmitter" recognized alongside nitric oxide (NO) and carbon monoxide (CO). H2S exhibits an array of biological effects in mammalian cells as revealed by studies showing important roles in the cardiovascular system, in cell signalling processes, post-translational modifications and in the immune system. Regarding the latter, using pharmacological and genetic approaches scientists have shown this molecule to have both pro- and anti-inflammatory effects in mammalian systems. The anti-inflammatory effects of H2S appeared to be due to its inhibitory action on the nuclear factor kappa beta signalling pathway; NF-kB representing a transcription factor involved in the regulation pro-inflammatory mediators like nitric oxide, prostaglandins, and cytokines. In contrast, results from several animal model describe a more complicated picture and report on pro-inflammatory effects linked to exposure to this molecule; linked to dosage used and point of administration of this molecule. Overall, roles for H2S in several inflammatory diseases spanning arthritis, atherosclerosis, sepsis, and asthma have been described by researchers. In light this work fascinating research, this chapter will cover H2S biology and its many roles in the immune system.

Do Long-Term Conservation Pasture Management Practices Influence Microbial Diversity and Antimicrobial Resistant Genes in Runoff?

Runoff from land-applied manure and poultry litter is one mechanism by which manure-borne bacteria are transported over large distances in the environment. There is a global concern that antimicrobial resistant (AMR) genes may be transmitted through the food chain from animal manures to soil to surface water. However, details are lacking on the ecology of AMR genes in water runoff as well as how conservation management practices may affect the runoff microbiome or minimize the movement of AMR genes. The aim of this study was to identify microbial community structure and diversity in water runoff following 14-years of poultry litter and cattle manure deposition and to evaluate the amount of AMR genes under five conventional and conservation pasture management strategies. Since 2004, all watersheds received annual poultry litter at a rate of 5.6 Mg ha-1 and were consistently managed. Surface runoff samples were collected from each watershed from 2018 to 2019, characterized using Illumina 16S rRNA gene amplicon sequencing and enumerated for four AMR-associated genes (ermB, sulI, intlI, and blactx-m-32 ) using quantitative PCR. Overall, long-term pasture management influenced water microbial community structure, with effects differing by year (p < 0.05). Bacterial richness (Chao1 index) was influenced by pasture management, with the lowest richness occurring in the control (nearby non-agricultural water source) and the greatest under fields that were hayed (no cattle presence). Runoff bacterial richness in watersheds increased following poultry litter applications, indicating poultry litter is a possible source of bacteria and altered runoff community structure. The blactx-m-32 gene was not detected in any surface water sample. The remaining three AMR genes were absent in the non-agricultural control, but present in agricultural samples. However, there was no impact (p > 0.05) from pasture management on the abundance of these genes, indicating both conventional and conservation practices have similar ecologies for these targets; however, there was a greater detection of sulI genes from runoff in continuously grazed systems in 2019, with hay being lowest in 2019. Results illustrate that the edge of field buffer strips may increase bacterial richness in water runoff, but these changes in richness do not greatly impact target AMR genes in the United States largest land-use category.

Conservation management practices reduce non-point source pollution from grazed pastures.

Producers in Northwest Arkansas and globally need alternative management practices to ensure long-term sustainable and economical use of poultry litter, which is an abundant source of valuable carbon (C), nitrogen (N) and phosphorus (P). Project objectives were to measure the efficacy of conservation management practices (i.e., pasture aeration and subsurface litter incorporation) to reduce nutrient runoff compared to poultry litter surface applications from small watersheds under rainfed and grazed conditions. Watersheds (0.23 ha each) were assigned a treatment [pasture aeration, subsurface litter incorporation, or surface application of litter (positive control)] on a Leadvale (fine-silty, siliceous, thermic Typic Fragiudult) silt loam. Poultry litter was applied annually to each watershed from 2007-2012. Over the 4-yr study period, runoff loads of NO3-N, total nitrogen (TN), soluble reactive phosphorus (SRP), and total phosphorus (TP) varied per conservation practice (P ≤ 0.05). Specifically, average annual loads of NO3-N, TN, SRP, and TP loads were reduced 49, 42, 28, and 35% following pasture aeration and by 78, 72, 55, and 59% from subsurface applying poultry litter, relative to surface applications, respectively. Greatest annual N loads and runoff corresponded with surface poultry litter applications, followed by pasture aeration, with subsurface incorporation of poultry litter resulting in lowest (P ≤ 0.05) TN and NO3-N loads. Overall, subsurface incorporation of poultry litter and pasture aeration are two promising conservation practices for reducing non-point source pollution in watersheds with nutrient imbalances. Further work needs to be done on factors influencing the efficacy of these conservation practices under rainfed conditions, as well as the economic feasibility of these conservation agricultural practices.

Variations in bacterial community structure and antimicrobial resistance gene abundance in cattle manure and poultry litter.

Cattle manure and poultry litter are widely used as fertilizers as they are excellent sources of nutrients; however, potential adverse environmental effects exist during land applications, due to the release of zoonotic bacteria and antimicrobial resistance (AMR) genes. This study was conducted to understand linkages between physiochemical composition, bacterial diversity, and AMR gene presence of cattle manure and poultry litter using quantitative polymerase chain reaction to enumerate four AMR genes (ermB, sulI, intlI, and blactx-m-32), Illumina sequencing of the 16 S region, and analysis of physical and chemical properties. Principal coordinate analysis of Bray-Curtis distance revealed distinct bacterial community structures between the two manure sources. Greater alpha diversity occurred in cattle manure compared to poultry litter (P < 0.05). Redundancy analysis showed a strong relationship between manure physiochemical and composition and bacterial abundance, with positive relationships occurring among electrical conductivity and carbon/nitrogen, and negative associations for total solids and soluble fractions of heavy metals. Cattle manure exhibited greater abundance of macrolide (ermB) and sulfonamide (sulI) resistant genes. Consequently, fresh cattle manure applications may result in greater potential spread of AMR genes to the soil-water environment (relative to poultry litter) and novel best management strategies (such as composting) may reduce the release of AMR genes to the soil-water environment.

Diet and Hydrogen Sulfide Production in Mammals.

Significance: In recent times, it has emerged that some dietary sulfur compounds can act on mammalian cell signaling systems via their propensity to release hydrogen sulfide (H2S). H2S plays important biochemical and physiological roles in the heart, gastrointestinal tract, brain, kidney, and immune systems of mammals. Reduced levels of H2S in cells and tissues correlate with a spectrum of pathophysiological conditions, including heart disease, diabetes, obesity, and altered immune function. Recent Advances: In the last decade, researchers have now begun to explore the mechanisms by which dietary-derived sulfur compounds, in addition to cysteine, can act as sources of H2S. This research has led to the identified several compounds, organic sulfides, isothiocyanates, and inorganic sulfur species including sulfate that can act as potential sources of H2S in mammalian cells and tissues. Critical Issues: We have summarised progress made in the identification of dietary factors that can impact on endogenous H2S levels in mammals. We also describe current research focused on how some sulfur molecules present in dietary plants, and associated chemical analogues, act as sources of H2S, and discuss the biological properties of these molecules as studied in a range of in vitro and in vivo systems. Future Directions: The identification of sulfur compounds in edible plants that can act as novel H2S releasing molecules is intriguing. Research in this area could inform future studies exploring the impact of diet on H2S levels in mammalian systems. Despite recent progress, additional work is needed to determine the mechanisms by which H2S is released from these molecules following ingestions of dietary plants in humans, whether the amounts of H2S produced is of physiological significance following the metabolism of these compounds in vivo, and if diet could be used to manipulated H2S levels in humans. Importantly, this will lead to a better understanding of the biological significance of H2S generated from dietary sources, and this information could be used in the development of plant breeding initiatives to increase the levels of H2S releasing sulfur compounds in crops, or inform dietary intervention strategies that could be used to alter the levels of H2S in humans.

Acute hyperosmolar hyperglycaemic state in cystic fibrosis-related diabetes caused by glucocorticoid and itraconazole interaction.

Hyperosmolar hyperglycaemic state (HHS) has not previously been reported in cystic fibrosis-related diabetes (CFRD). We report the case of a 15-year old boy with stable CFRD who developed acute HHS after treatment with glucocorticoids and itraconazole for presumed allergic broncho-pulmonary aspergillosis (ABPA). This case highlights the dangerous and preventable combination of high glucose intake, glucocorticoids and itraconazole inhibition of CYP3A4 (with resultant glucocorticoid accumulation) that can result in a state of life- threatening HHS in an adolescent with previously stable CFRD.

Multilevel mobile health approach to improve cardiovascular health in resource-limited communities with Step It Up: a randomised controlled trial protocol targeting physical activity.

INTRODUCTION: Although physical activity (PA) reduces cardiovascular disease (CVD) risk, physical inactivity remains a pressing public health concern, especially among African American (AA) women in the USA. PA interventions focused on AA women living in resource-limited communities with scarce PA infrastructure are needed. Mobile health (mHealth) technology can increase access to PA interventions. We describe the development of a clinical protocol for a multilevel, community-based, mHealth PA intervention for AA women. METHODS AND ANALYSIS: An mHealth intervention targeting AA women living in resource-limited Washington, DC communities was developed based on the socioecological framework for PA. Over 6 months, we will use a Sequential Multi-Assignment, Randomized Trial approach to compare the effects on PA of location-based remote messaging (named 'tailored-to-place') to standard remote messaging in an mHealth intervention. Participants will be randomised to a remote messaging intervention for 3 months, at which point the intervention strategy will adapt based on individuals' PA levels. Those who do not meet the PA goal will be rerandomised to more intensive treatment. Participants will be followed for another 3 months to determine the contribution of each mHealth intervention to PA level. This protocol will use novel statistical approaches to account for the adaptive strategy. Finally, effects of PA changes on CVD risk biomarkers will be characterised. ETHICS AND DISSEMINATION: This protocol has been developed in partnership with a Washington, DC-area community advisory board to ensure feasibility and acceptability to community members. The National Institutes of Health Intramural IRB approved this research and the National Heart, Lung, and Blood Institute provided funding. Once published, results of this work will be disseminated to community members through presentations at community advisory board meetings and our quarterly newsletter. TRIAL REGISTRATION NUMBER: NCT03288207.

Antimicrobial resistant gene prevalence in soils due to animal manure deposition and long-term pasture management.

The persistence of antimicrobial resistant (AMR) genes in the soil-environment is a concern, yet practices that mitigate AMR are poorly understood, especially in grasslands. Animal manures are widely deposited on grasslands, which are the largest agricultural land-use in the United States. These nutrient-rich manures may contain AMR genes. The aim of this study was to enumerate AMR genes in grassland soils following 14-years of poultry litter and cattle manure deposition and evaluate if best management practices (rotationally grazed with a riparian (RBR) area and a fenced riparian buffer strip (RBS), which excluded cattle grazing and poultry litter applications) relative to standard pasture management (continuously grazed (CG) and hayed (H)) minimize the presence and amount of AMR genes. Quantitative PCR (Q-PCR) was performed to enumerate four AMR genes (ermB, sulI, intlI, and blactx-m-32 ) in soil, cattle manure, and poultry litter environments. Six soil samples were additionally subjected to metagenomic sequencing and resistance genes were identified from assembled sequences. Following 14-years of continuous management, ermB, sulI, and intlI genes in soil were greatest (P < 0.05) in samples collected under long-term continuous grazing (relative to conservation best management practices), under suggesting overgrazing and continuous cattle manure deposition may increase AMR gene presence. In general, AMR gene prevalence increased downslope, suggesting potential lateral movement and accumulation based on landscape position. Poultry litter had lower abundance of AMR genes (ermB, sulI, and intlI) relative to cattle manure. Long-term applications of poultry litter increased the abundance of sulI and intlI genes in soil (P < 0.05). Similarly, metagenomic shotgun sequencing revealed a greater total number of AMR genes under long-term CG, while fewer AMR genes were found in H (no cattle manure) and RBS (no animal manure or poultry litter). Results indicate long-term conservation pasture management practices (e.g., RBS and RBR) and select animal manure (poultry litter inputs) may minimize the presence and abundance of AMR genes in grassland soils.

Long-term effects of grazing management and buffer strips on phosphorus runoff from pastures fertilized with poultry litter.

Phosphorus (P) runoff from pastures can cause accelerated eutrophication of surface waters. However, few long-term studies have been conducted on the effects of best management practices, such as rotational grazing and/or buffer strips on P losses from pastures. The objective of this study was to evaluate the long-term effects of grazing management and buffer strips on P runoff from pastures receiving annual (5.6 Mg ha-1 ) poultry litter applications. A 14-yr study was conducted on 15 small watersheds (0.14 ha) with five treatments: hayed (H), continuously grazed (CG), rotationally grazed (R), rotationally grazed with an unfertilized buffer strip (RB), and rotationally grazed with an unfertilized fenced riparian buffer (RBR). Runoff samples were collected using automatic samplers during runoff events. Average annual runoff volumes from H (40 mm yr-1 ) and RBR (48 mm yr-1 ) were lower than CG and RB, which were both 65 mm yr-1 , and from R (67 mm yr-1 ). Rotational grazing alone did not reduce P loads compared with continuous grazing (1.88 and 1.71 kg P ha-1 for R and CG, respectively). However, compared with CG, total P losses from RB pastures were reduced 36% with unfertilized buffer strips (1.21 kg P ha-1 ), 60% in RBR watersheds with unfertilized fenced riparian buffer strips (0.74 kg P ha-1 ), and 49% by converting pastures to hayfields (0.97 kg P ha-1 ). Hence, the use of unfertilized buffer strips, unfertilized fenced riparian buffer strips, or converting pastures to hayfields are effective best management practices for reducing P runoff in U.S. pasture systems.

Lifespan and healthspan benefits of exogenous H2S in C. elegans are independent from effects downstream of eat-2 mutation.

Caloric restriction (CR) is one of the most effective interventions to prolong lifespan and promote health. Recently, it has been suggested that hydrogen sulfide (H2S) may play a pivotal role in mediating some of these CR-associated benefits. While toxic at high concentrations, H2S at lower concentrations can be biologically advantageous. H2S levels can be artificially elevated via H2S-releasing donor drugs. In this study, we explored the function of a novel, slow-releasing H2S donor drug (FW1256) and used it as a tool to investigate H2S in the context of CR and as a potential CR mimetic. We show that exposure to FW1256 extends lifespan and promotes health in Caenorhabditis elegans (C. elegans) more robustly than some previous H2S-releasing compounds, including GYY4137. We looked at the extent to which FW1256 reproduces CR-associated physiological effects in normal-feeding C. elegans. We found that FW1256 promoted healthy longevity to a similar degree as CR but with fewer fitness costs. In contrast to CR, FW1256 actually enhanced overall reproductive capacity and did not reduce adult body length. FW1256 further extended the lifespan of already long-lived eat-2 mutants without further detriments in developmental timing or fertility, but these lifespan and healthspan benefits required H2S exposure to begin early in development. Taken together, these observations suggest that FW1256 delivers exogenous H2S efficiently and supports a role for H2S in mediating longevity benefits of CR. Delivery of H2S via FW1256, however, does not mimic CR perfectly, suggesting that the role of H2S in CR-associated longevity is likely more complex than previously described.