Macrophages Facilitate Electrical Conduction in the Heart.

Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.

Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge.

Myocardial infarction, stroke, and sepsis trigger systemic inflammation and organism-wide complications that are difficult to manage. Here, we examined the contribution of macrophages residing in vital organs to the systemic response after these injuries. We generated a comprehensive catalog of changes in macrophage number, origin, and gene expression in the heart, brain, liver, kidney, and lung of mice with myocardial infarction, stroke, or sepsis. Predominantly fueled by heightened local proliferation, tissue macrophage numbers increased systemically. Macrophages in the same organ responded similarly to different injuries by altering expression of tissue-specific gene sets. Preceding myocardial infarction improved survival of subsequent pneumonia due to enhanced bacterial clearance, which was caused by IFNÉ£ priming of alveolar macrophages. Conversely, EGF receptor signaling in macrophages exacerbated inflammatory lung injury. Our data suggest that local injury activates macrophages in remote organs and that targeting macrophages could improve resilience against systemic complications following myocardial infarction, stroke, and sepsis.

Person-specific dynamics between negative emotions and suicidal thoughts.

INTRODUCTION: Recent technology has enabled researchers to collect ecological momentary assessments (EMA) to examine within-person correlates of suicidal thoughts. Prior studies examined generalized temporal dynamics of emotions and suicidal thinking over brief periods, but it is not yet known how variable these processes are across people. METHOD: We use data EMA data delivered over two weeks with youth/young adults (N = 60) who reported past year self-injurious thoughts/behaviors. We used group iterative multiple model estimation (GIMME) to model group- and person-specific associations of negative emotions (i.e., fear, sadness, shame, guilt, and anger) and suicidal thoughts. RESULTS: 29 participants (48.33%) reported at least one instance of a suicidal thought and were included in GIMME models. In group level models, we consistently observed autoregressive effects for suicidal thoughts (e.g., earlier thoughts predicting later thoughts), although the magnitude and direction of this link varied from person-to-person. Among emotions, sadness was most frequently associated with contemporaneous suicidal thoughts, but this was evident for less than half of the sample, while other emotional correlates of suicidal thoughts broadly differed across people. No emotion variable was linked to future suicidal thoughts in >14% of the sample, CONCLUSIONS: Emotion-based correlates of suicidal thoughts are heterogeneous across people. Better understanding of the individual-level pathways maintaining suicidal thoughts/behaviors may lead to more effective, personalized interventions.

Mechanistic insights on age-related changes in heart-aorta-brain hemodynamic coupling using a pulse wave model of the entire circulatory system.

Age-related changes in aortic biomechanics can impact the brain by reducing blood flow and increasing pulsatile energy transmission. Clinical studies have shown that impaired cardiac function in patients with heart failure is associated with cognitive impairment. Although previous studies have attempted to elucidate the complex relationship between age-associated aortic stiffening and pulsatility transmission to the cerebral network, they have not adequately addressed the effect of interactions between aortic stiffness and left ventricle (LV) contractility (neither on energy transmission nor on brain perfusion). In this study, we use a well-established and validated one-dimensional blood flow and pulse wave computational model of the circulatory system to address how age-related changes in cardiac function and vasculature affect the underlying mechanisms involved in the LV-aorta-brain hemodynamic coupling. Our results reveal how LV contractility affects pulsatile energy transmission to the brain, even with preserved cardiac output. Our model demonstrates the existence of an optimal heart rate (near the normal human heart rate) that minimizes pulsatile energy transmission to the brain at different contractility levels. Our findings further suggest that the reduction in cerebral blood flow at low levels of LV contractility is more prominent in the setting of age-related aortic stiffening. Maintaining optimal blood flow to the brain requires either an increase in contractility or an increase in heart rate. The former consistently leads to higher pulsatile power transmission, and the latter can either increase or decrease subsequent pulsatile power transmission to the brain.NEW & NOTEWORTHY We investigated the impact of major aging mechanisms of the arterial system and cardiac function on brain hemodynamics. Our findings suggest that aging has a significant impact on heart-aorta-brain coupling through changes in both arterial stiffening and left ventricle (LV) contractility. Understanding the underlying physical mechanisms involved here can potentially be a key step for developing more effective therapeutic strategies that can mitigate the contributions of abnormal LV-arterial coupling toward neurodegenerative diseases and dementia.

NOD-like receptor protein 3 activation causes spontaneous inflammation and fibrosis that mimics human NASH.

BACKGROUND AND AIMS: The NOD-like receptor protein 3 (NLRP3) inflammasome is a central contributor to human acute and chronic liver disease, yet the molecular and cellular mechanisms by which its activation precipitates injury remain incompletely understood. Here, we present single cell transcriptomic profiling of livers from a global transgenic tamoxifen-inducible constitutively activated Nlrp3A350V mutant mouse, and we investigate the changes in parenchymal and nonparenchymal liver cell gene expression that accompany inflammation and fibrosis. APPROACH AND RESULTS: Our results demonstrate that NLRP3 activation causes chronic extramedullary myelopoiesis marked by myeloid progenitors that differentiate into proinflammatory neutrophils, monocytes, and monocyte-derived macrophages. We observed prominent neutrophil infiltrates with increased Ly6gHI and Ly6gINT cells exhibiting transcriptomic signatures of granulopoiesis typically found in the bone marrow. This was accompanied by a marked increase in Ly6cHI monocytes differentiating into monocyte-derived macrophages that express transcriptional programs similar to macrophages of NASH models. NLRP3 activation also down-regulated metabolic pathways in hepatocytes and shifted hepatic stellate cells toward an activated profibrotic state based on expression of collagen and extracellular matrix regulatory genes. CONCLUSIONS: These results define the single cell transcriptomes underlying hepatic inflammation and fibrosis precipitated by NLRP3 activation. Clinically, our data support the notion that NLRP3-induced mechanisms should be explored as therapeutic target in NASH-like inflammation.

The relation between stress and impulsivity during the first year of college.

OBJECTIVE: Previous research has established that short-term and persistent stress negatively impact mental health, with one proposed consequence being increased impulsivity. The present study tests the short-term and persistent associations between stress and three facets of global self-reports of impulsivity: negative urgency, lack of premeditation, and lack of perseverance, among young adults across 6 months of their first year of college. METHOD: College freshmen (n = 362) completed self-report questionnaires assessing stress, negative urgency, lack of premeditation, and lack of perseverance three times over a 6-month period. Pre-registered analyses were conducted using multilevel growth curve models. RESULTS: Confirmatory analyses suggested that persistent stress was associated with higher levels of negative urgency and trajectories of worsening lack of perseverance over time, while short-term stress was associated with higher negative urgency. Lack of premeditation was not robustly associated with stress. CONCLUSIONS: While both persistent and short-term exposure to stress may be associated with some facets of global self-reports of impulsivity, the relations vary across facets of impulsivity. Overall, negative urgency was the most robustly associated with stress on both time scales, which suggests that this facet of impulsivity may be the most impacted in the context of stress in the first year of college.

Pathways of personality and learning risk for addictive behaviors: A systematic review of mediational research on the acquired preparedness model.

OBJECTIVE: The Acquired Preparedness (AP) model proposes that impulsive personality traits predispose some individuals to learn certain behavior-outcome associations (expectancies), and that these expectancies in turn influence the escalation of risky behaviors. This theory has been applied to the development of behaviors such as drinking, drug use, gambling, and disordered eating. In the current study, we aimed to summarize empirical tests of this model over the 20 years since it was proposed. METHOD: We used a descriptive approach to summarize tests of mediation across 50 studies involving n = 21,715 total participants. RESULTS: We observed a consistent effect of personality on expectancies (median effect size = .22), of expectancies on behavior (.24), and a small mediated effect (.05) of personality on behavior via expectancies. Impulsive traits that involve positive or negative affect showed the most consistent support for AP, as did positive expectancies. Most studies testing AP focused on alcohol, but research on other behaviors also showed support for AP. CONCLUSIONS: The literature appears to support a small mediated effect consistent with the AP model. Future research should continue to clarify which AP pathways are most influential in explaining risky behaviors, and supplement correlational research with experimental and quasi-experimental designs.

Hepatic gap junctions amplify alcohol liver injury by propagating cGAS-mediated IRF3 activation.

Alcohol-related liver disease (ALD) accounts for the majority of cirrhosis and liver-related deaths worldwide. Activation of IFN-regulatory factor (IRF3) initiates alcohol-induced hepatocyte apoptosis, which fuels a robust secondary inflammatory response that drives ALD. The dominant molecular mechanism by which alcohol activates IRF3 and the pathways that amplify inflammatory signals in ALD remains unknown. Here we show that cytoplasmic sensor cyclic guanosine monophosphate-adenosine monophosphate (AMP) synthase (cGAS) drives IRF3 activation in both alcohol-injured hepatocytes and the neighboring parenchyma via a gap junction intercellular communication pathway. Hepatic RNA-seq analysis of patients with a wide spectrum of ALD revealed that expression of the cGAS-IRF3 pathway correlated positively with disease severity. Alcohol-fed mice demonstrated increased hepatic expression of the cGAS-IRF3 pathway. Mice genetically deficient in cGAS and IRF3 were protected against ALD. Ablation of cGAS in hepatocytes only phenocopied this hepatoprotection, highlighting the critical role of hepatocytes in fueling the cGAS-IRF3 response to alcohol. We identified connexin 32 (Cx32), the predominant hepatic gap junction, as a critical regulator of spreading cGAS-driven IRF3 activation through the liver parenchyma. Disruption of Cx32 in ALD impaired IRF3-stimulated gene expression, resulting in decreased hepatic injury despite an increase in hepatic steatosis. Taken together, these results identify cGAS and Cx32 as key factors in ALD pathogenesis and as potential therapeutic targets for hepatoprotection.

Field-scale nutrient loss assessment following cover crop and manure rate change.

Eutrophication due to elevated nitrogen (N) and phosphorus (P) loss from croplands remains one of the most pressing water quality issues throughout the world. Understanding the effect of implementing conservation management practices is critical for meeting nutrient reduction goals as well as informing conservation programs and policies. A before-after-control-impact (BACI) analysis was used to evaluate the individual and combined effect of cover crops and manure application rate on discharge and nutrient loss using six water years (WY2014-WY2019) of measured data across four distinct drainage zones (1X-NCC; 1X-CC; 2X-NCC; 2X-CC) within an Ohio, USA, crop production field. White mustard significantly reduced mean monthly nitrate (NO3--N) concentration regardless of manure application rate (i.e., 65 m3 ha-1 and 130 m3 ha-1). However, neither the use of white mustard, doubling manure rate, or the combination of the two had a significant impact on mean monthly drainage discharge, dissolved-reactive P (DRP), or total P (TP) loss. Seasonal analysis confirmed that NO3--N concentration in the cover crop zones was signficantly less in fall, winter, and spring. However, significant increases in spring discharge, NO3--N, DRP, and TP loads as well as TP concentration were noted with cover crop and greater manure rate treatments. These findings confirm that cover crops have a reducing effect on NO3--N concentration but may not have any effect on addressing P concerns. Further research is warranted; however, this study highlights that the resource concern (e.g., N or P) should be considered prior to implementing cover crops as a conservation management practice.

The relations between real-time use of emotion regulation strategies and anxiety and depression symptoms.

OBJECTIVE: How individuals differentially implement specific emotion regulation (ER) strategies is a critical indicator of the progression of depressive and anxiety disorders. Symptoms of anxiety and depression may be associated with differences in ER, but little evidence to date had examined whether anxiety and depression were associated with individual differences in the real-time use of ER strategies. METHODS: This study used ecological momentary assessment (EMA) in two samples (n = 276) of undergraduate students from a single university who were assessed for 8-10 days. Baseline surveys captured participant self-reported anxiety symptoms and depressive symptoms using the PROMIS-Anxiety scale and the PROMIS-Depression scale, respectively. We measured ER through EMA-adapted prompts from the Cognitive Emotion Regulation Questionnaire (CERQ), which participants received on their internet-enabled cell phones. In pre-registered analyses, we tested the associations between anxiety symptoms with the use of discrete ER strategies in EMA using generalized estimating equations with a log-link function to account for nesting of EMA observations within participants, and further tested whether the findings generalized to depression (not pre-registered). RESULTS: Symptoms of anxiety and depression were associated with greater odds of using both maladaptive and adaptive ER strategy use during the EMA period, and with lower odds of reporting no strategy use. Moreover, associations were generally stronger for maladaptive than adaptive ER strategies. CONCLUSION: Anxiety and depressive symptoms are related to increased regulatory efforts overall, and results suggest that individuals with anxiety and depressive symptoms may be especially prone to use maladaptive ER strategies. Tracking ER strategies in a natural environment can further inform our understanding of how anxious and depressed individuals attempt to regulate emotions.

The Power of Single-Cell Analysis for the Study of Liver Pathobiology.

Single cell transcriptomics has emerged as a powerful lens through which to study the molecular diversity of complex tissues such as the liver, during health and disease, both in animal models and in humans. The earliest gene expression methods measured bulk tissue RNA, but the results were often confusing because they derived from the combined transcriptomes of many different cell types in unknown proportions. To better delineate cell-type-specific expression, investigators developed cell isolation, purification, and sorting protocols, yet still, the RNA derived from ensembles of cells obscured recognition of cellular heterogeneity. Profiling transcriptomes at the single-cell level has opened the door to analyses that were not possible in the past. In this review, we discuss the evolution of single cell transcriptomics and how it has been applied for the study of liver physiology and pathobiology to date.

Low mortality in SARS-CoV-2 infected heart transplant recipients at a single center.

Immunosuppressed heart transplant (HT) recipients are thought to be at higher risk of infection and mortality from SARS-CoV-2 infection coronavirus disease 2019 (COVID-19); however, evidence guiding management of HT patients are limited. Retrospective search of electronic health records from February 2020 to February 2021, identified 28 HT recipients out of 400 followed by UC San Diego who tested positive for SARS-CoV-2. Patient demographics, COVID-19 directed therapies, hospital course and outcomes were compared to control HT recipients who tested negative for SARS-CoV-2 during the same period (n = 80). Among 28 HT recipients who tested positive for SARS-CoV-2, 15 were admitted to the hospital and 13 were monitored closely as outpatients. Among inpatients, five developed severe illness and two died (7% mortality). Nine patients were treated with remdesivir, and four received dexamethasone and remdesivir. Two outpatients received neutralizing monoclonal antibody therapy and one outpatient received dexamethasone for persistent dyspnea. Immunosuppressed HT recipients, especially Hispanic patients and patients with higher body mass index, were at greater risk of infection and mortality from COVID-19 than the general population. Use of remdesivir and dexamethasone may have improved outcomes in our HT recipients compared to HT recipients at other centers.

Behavioral Willingness, Descriptive Normative Perceptions, and Prescription Stimulant Misuse among Young Adults 18-20.

Objective: It is critical to gain further understanding of etiologic factors, such as descriptive normative perceptions and behavioral willingness, that are associated with prescription stimulant misuse (PSM) among young adults. Our primary hypotheses were that descriptive normative perceptions for PSM (i.e., perceptions of how much and how often others engage in PSM) and perceived peer willingness (i.e., perceptions of how open others are to PSM under certain circumstances) would be positively associated with higher willingness to engage in PSM, which in turn would account for significant shared variance with self-reported PSM. Method: Data were collected from a U.S. sample of 18-20-year-olds (N = 1,065; 54.5% females; 70.5% White) recruited for a larger study on alcohol-related risky sexual behavior. Results: Findings indicated higher descriptive normative perceptions and higher perceived peer willingness were associated with higher participants' willingness to engage in PSM. Participants' own willingness was positively associated with PSM. Finally, participants' own willingness to use, descriptive normative perceptions, and perceived peer willingness were associated with higher willingness to engage in PSM, which accounted for significant shared variance with self-reported PSM. Conclusions: Findings suggest the potential utility of personalized feedback interventions for PSM that focus on constructs such as descriptive normative perceptions and behavioral willingness.

Interpreting Interaction Effects in Generalized Linear Models of Nonlinear Probabilities and Counts.

Psychology research frequently involves the study of probabilities and counts. These are typically analyzed using generalized linear models (GLMs), which can produce these quantities via nonlinear transformation of model parameters. Interactions are central within many research applications of these models. To date, typical practice in evaluating interactions for probabilities or counts extends directly from linear approaches, in which evidence of an interaction effect is supported by using the product term coefficient between variables of interest. However, unlike linear models, interaction effects in GLMs describing probabilities and counts are not equal to product terms between predictor variables. Instead, interactions may be functions of the predictors of a model, requiring nontraditional approaches for interpreting these effects accurately. Here, we define interactions as change in a marginal effect of one variable as a function of change in another variable, and describe the use of partial derivatives and discrete differences for quantifying these effects. Using guidelines and simulated examples, we then use these approaches to describe how interaction effects should be estimated and interpreted for GLMs on probability and count scales. We conclude with an example using the Adolescent Brain Cognitive Development Study demonstrating how to correctly evaluate interaction effects in a logistic model.

A crisis of generalizability or a crisis of constructs?

Psychologists wish to identify and study the mechanisms and implications of nomothetic constructs that reveal truths about human nature and span across operationalizations. To achieve this goal, psychologists should spend more time carefully describing and measuring constructs across a wide range of methods and measures, and less time rushing to explain and predict.

Examining interactions between negative emotionality and effortful control in predicting preadolescent adjustment problems.

Negative emotionality and effortful control consistently predict child adjustment, yet few studies explore their interactive effects on adjustment. In concurrent and longitudinal (one-year follow-up) analyses, we examined negative emotionality-by-effortful control interactions in predicting anxiety, depression, and conduct problems in 214 children aged 8-12. Temperament was assessed using behavioral tasks measuring fear, frustration, executive control, and delay ability. An interaction between frustration and executive control predicting conduct problems was observed; higher executive control was related to fewer concurrent conduct problems for those moderate to high in frustration, but did not predict conduct problems for those low in frustration. This interaction did not predict conduct problems one year later. No support was found for negative emotionality-by-effortful control interactions predicting anxiety or depression. Our findings highlight the importance of executive control during preadolescence and provide mixed evidence regarding whether facets of negative emotionality and executive control interact with one another to influence adjustment.

Primary and secondary caregiver depressive symptoms and family functioning following a pediatric cancer diagnosis: an exploration of the buffering hypothesis.

OBJECTIVE: After diagnosis, caregivers of children with cancer, particularly mothers or primary caregivers (PCs), often show elevated depressive symptoms which may negatively impact family functioning. We tested PC and secondary caregiver (SC) depressive symptoms as predictors of family, co-parenting, and marital functioning and whether having a non-depressed SC buffers against potential negative effects of PC depressive symptoms. METHODS: Families (N = 137) were recruited from two major children's hospitals following a diagnosis of pediatric cancer. Caregivers completed self-report measures of depressive symptoms (Center for Epidemiological Studies-Depression Scale; Depression, Anxiety, and Stress Scale) and marital functioning (Dyadic Adjustment Scale) at 1-month post-diagnosis. A subset of families (n = 75) completed videotaped interaction tasks at approximately 3-months post-diagnosis that were coded for family and co-parenting interactions. RESULTS: Higher PC depressive symptoms at 1-month post-diagnosis was associated with higher adaptability and lower conflict in family functioning. PC depressive symptoms were also associated lower dyadic consensus and lower dyadic satisfaction. SC depressive symptoms were not significantly associated with any family/co-parenting/marital functioning variables. Significant interaction analyses suggested that SC depressive symptoms moderated the effect of PC depressive symptoms on family cohesion, withdrawn parenting, and affective expression in the marriage, such that the relationship between PC depressive symptoms and poorer functioning was attenuated when SC depressive symptoms were at low or average levels. CONCLUSIONS: Having a nondepressed SC buffered against negative effects of PC depressive symptoms on certain domains of family, coparenting, and marital functioning. SCs may play a protective role for families of children with cancer.

Novel Multiplex and Loop-Mediated Isothermal Amplification Assays for Rapid Species and Mating-Type Identification of Oculimacula acuformis and O. yallundae (Causal Agents of Cereal Eyespot), and Application for Detection of Ascospore Dispersal and In Planta Use.

Eyespot, caused by the related fungal pathogens Oculimacula acuformis and O. yallundae, is an important cereal stem-base disease in temperate parts of the world. Both species are dispersed mainly by splash-dispersed conidia but are also known to undergo sexual reproduction, yielding apothecia containing ascospores. Field diagnosis of eyespot can be challenging, with other pathogens causing similar symptoms, which complicates eyespot management strategies. Differences between O. acuformis and O. yallundae (e.g., host pathogenicity and fungicide sensitivity) require that both be targeted for effective disease management. Here, we develop and apply two molecular methods for species-specific and mating-type (MAT1-1 or MAT1-2) discrimination of O. acuformis and O. yallundae isolates. First, a multiplex PCR-based diagnostic assay targeting the MAT idiomorph region was developed, allowing simultaneous determination of both species and mating type. This multiplex PCR assay was successfully applied to type a global collection of isolates. Second, the development of loop-mediated isothermal amplification (LAMP) assays targeting ß-tubulin sequences, which allow fast (<9 min) species-specific discrimination of global O. acuformis and O. yallundae isolates, is described. The LAMP assay can detect very small amounts of target DNA (1 pg) and was successfully applied in planta. In addition, mating-type-specific LAMP assays were also developed for rapid (<12 min) genotyping of O. acuformis and O. yallundae isolates. Finally, the multiplex PCR-based diagnostic was applied, in conjunction with spore trapping in field experiments, to provide evidence of the wind dispersal of ascospores from a diseased crop. The results indicate an important role of the sexual cycle in the dispersal of eyespot.

Prevalence, predictors and trends of opioid prescribing for lower back pain in United States emergency departments.

WHAT IS KNOWN AND OBJECTIVE: Current evidence-based guidelines for the treatment of acute low back pain (ALBP) recommend the use of opioid medications only after failure of nonpharmacological therapy, non-steroidal anti-inflammatory drugs and skeletal muscle relaxants and after thorough evaluation of risks and benefits. Despite this recommendation and the state of the opioid epidemic in the United States (US), opioids remain a common drug of choice for ALBP in the emergency department (ED). The purpose of this study was to quantify the prevalence and identify predictors of opioid prescribing for acute lower back pain (ALBP) in emergency departments (EDs) in the United States. METHODS: This was a national, cross-sectional study of the National Hospital Ambulatory Care Survey from 2013-2016. ED visits for patients aged ≥18 years treated for ALBP were included. Patients presenting with specified reasons that an opioid may be indicated were excluded. The primary endpoint was frequency of opioids prescribed. A multivariate logistic regression model identified patient- and provider-level predictors of opioid use. RESULTS AND DISCUSSION: This analysis included 2260 visits for ALBP. Opioids were prescribed in 32.3% of visits. Positive predictors of opioid prescribing were pain score of 7-10 (OR 1.85; 95% CI 1.26-2.70), and patients seen in the Southern (OR 2.53; 95% CI 1.47-4.36) or Western US (OR 2.10; 95% CI 1.19-3.70). Opioids were prescribed less often to patients who received a NSAID or acetaminophen (OR 0.38; 95% CI 0.28-0.52 and OR 0.03; 95% CI 0.01-0.10, respectively). WHAT IS NEW AND CONCLUSION: Opioid prescribing rates for ALBP remain high and the predictors identified demonstrate that this prescribing pattern is not uniformly distributed across the patient and provider characteristics studied.

Cover crops differentially influenced nitrogen and phosphorus loss in tile drainage and surface runoff from agricultural fields in Ohio, USA.

Nitrogen (N) and phosphorus (P) loss from crop production agriculture is transported to adjacent and downstream water bodies, resulting in negative environmental impacts including harmful and nuisance algal blooms. Cover crops are a conservation management practice that replaces bare soil with vegetation outside of the cash crop growing season, purportedly reducing N and P loss by increasing water and nutrient demand in agroecosystems. In this study, we compared nitrate (NO3--N), total N (TN), dissolved reactive P (DRP), and total P (TP) loads in subsurface (tile) drainage and surface runoff from fields with cover crop management (CC) and fields without cover crop management (NoCC) using continuous monitoring data from 40 agricultural fields located throughout northcentral Ohio, United States (US). We found that average monthly tile NO3--N and TN loads from CC fields were ~50% less than NoCC fields, while average monthly tile discharge, DRP, and TP loads did not differ between CC and NoCC fields. Cover crops also did not significantly influence average monthly surface metrics. Cover crops reduced monthly totals of tile NO3--N and TN loads by ~1.0-2.6 kg N ha-1 from January to June (winter and spring), coinciding with critical periods of nutrient loss from agroecosystems in the midwestern US, but increased monthly totals of tile DRP (by 0.4-12.1 g DRP ha-1) and TP (by 1.2-31.6 g TP ha-1) loads during some months. We found similar patterns at the annual time scale whereby CC fields had lesser cumulative annual totals of tile NO3--N and TN but greater cumulative annual totals of tile DRP and TP. These results show that the influence of cover crops on N loads, but not P, were consistent across temporal scales of examination, demonstrating that cover crops effectively increased N demand and mitigated N losses from agricultural fields. The variable influence of cover crops on P loads underscores the need for greater understanding of the factors and mechanisms that control P loss in systems that include cover crop management. Furthermore, these findings stress the importance of identifying and selecting conservation management practices tailored to the natural resource concern.