A meta-analysis highlights globally widespread potassium limitation in terrestrial ecosystems.

Potassium (K+ ) is the most abundant inorganic cation in plant cells, playing a critical role in various plant functions. However, the impacts of K on natural terrestrial ecosystems have been less studied compared with nitrogen (N) and phosphorus (P). Here, we present a global meta-analysis aimed at quantifying the response of aboveground production to K addition. This analysis is based on 144 field K fertilization experiments. We also investigate the influences of climate, soil properties, ecosystem types, and fertilizer regimes on the responses of aboveground production. We find that: K addition significantly increases aboveground production by 12.3% (95% CI: 7.4-17.5%), suggesting a widespread occurrence of K limitation across terrestrial ecosystems; K limitation is more prominent in regions with humid climates, acidic soils, or weathered soils; the effect size of K addition varies among climate zones/regions, and is influenced by multiple factors; and previous N : K and K : P thresholds utilized to detect K limitation in wetlands cannot be applied to other biomes. Our findings emphasize the role of K in limiting terrestrial productivity, which should be integrated into future terrestrial ecosystems models.

Role of the luminal composition on intestinal metal toxicity, bioavailability and bioreactivity: An in vitro approach based on the cell line RTgutGC.

The bioavailability of metal complexes is poorly understood. To evaluate bioavailability and toxicity of neutral and charged complexes as well as free metal ions, Visual Minteq, a chemical equilibrium model, was used to design media containing different metal species. Two non-essential (silver and cadmium) and two essential (copper and zinc) metals were selected. The rainbow trout (Oncorhynchus mykiss) gut cell line (RTgutGC) was used to investigate bioavailability, bioreactivity and toxicity of the different metal species. Toxicity was measured using a multiple endpoint cytotoxicity assay, bioavailability by measuring intracellular metal concentration, and bioreactivity by quantification of mRNA level of the metal responsive genes, metallothionein (MT), glutathione reductase (GR) and zinc transporter 1 (ZnT1). Speciation calculations showed that silver and cadmium preferentially bind chloride, copper phosphate and bicarbonate, and zinc remained primarily as a free ion. Cysteine avidly complexed with all metals reducing toxicity, bioavailability and bioreactivity. Silver and copper toxicity was not affected by inorganic metal speciation, whereas cadmium and zinc toxicity was decreased by chloride complexation. Moreover, reduction of calcium concentration in the medium increased toxicity and bioavailability of cadmium and zinc. Bioavailability of silver and zinc was reduced by low chloride while cadmium bioavailability was increased by low chloride and in presence of bicarbonate. Copper bioavailability was not affected by the medium composition. Cadmium and silver were more bioreactive, independently from the medium composition, in comparison to copper and zinc (i.e., higher induction of MT and GR). Cadmium was the only metal able to induce MT in presence of cysteine. ZnT1 was induced by cadmium in low-chloride, by zinc in low-chloride low-calcium and by cadmium and copper in the bicarbonate media. Overall, this study demonstrates that metal complexation alone is not sufficient to explain metal toxicity, and that anion exchange mechanisms play a role in metal uptake and bioreactivity.

Pediatric Antibiotic Prescribing and Utilization Practices for RTIs at Private Urgent Care Centers.

Data on pediatric antibiotic prescribing and utilization practices at urgent care centers (UCC) remain limited. In this study, an electronic medical record-based review of UCC encounters for respiratory tract infections (RTI) of patients belonging to one mid-sized pediatric practice was performed. Antibiotic prescribing and guideline adherence were compared between UCCs that were staffed exclusively by pediatric-trained providers to those staffed otherwise. Of a total of 457 RTI visits, 330 (72%) occurred at the pediatric UCC. Across all bacterial RTIs, 82% of encounters at the pediatric UCC were guideline-adherent versus 59% at nonpediatric UCCs (P < .001). At nonpediatric UCCs, pharyngitis was the most common RTI encounter diagnosis (40%), and full streptococcal management guideline adherence was 41%. While 93% of RTI-UCC encounters for <2 years were at pediatric UCCs, the majority of children >10 presented to nonpediatric UCCs. RTI guideline education to UCCs should be a focus of ambulatory stewardship efforts.

Stress and depression in undergraduate students during the COVID-19 pandemic: Nursing students compared to undergraduate students in non-nursing majors.

BACKGROUND: The COVID-19 pandemic exacerbated an already alarming mental health crisis on college campuses. Nursing students were uniquely impacted through the loss of clinical practicum experiences. PURPOSE: The purpose of this study was to explore relationships between student perceptions of life-stress and depressive symptoms during the COVID-19 pandemic in nursing students compared to students in other academic disciplines. A secondary purpose of this study was to understand nursing student perceptions of how the COVID-19 pandemic impacted their educational experience. METHODS: School-related life stress and depression measures were studied in a cross-section of 2326 undergraduate students using an anonymous online survey. Follow-up qualitative data were collected (N = 12) to further explore relationships between school-related life stress and depression in nursing students. RESULTS: Nursing students had higher levels of student-life stress but fewer depressive symptoms than students in any other academic major. Students related that social support and belongingness were critical to their academic perseverance. CONCLUSIONS: Differences between nursing and non-nursing students are likely due to a multifactorial combination of social support, resilience, and posttraumatic growth.

COSORE: A community database for continuous soil respiration and other soil-atmosphere greenhouse gas flux data.

Globally, soils store two to three times as much carbon as currently resides in the atmosphere, and it is critical to understand how soil greenhouse gas (GHG) emissions and uptake will respond to ongoing climate change. In particular, the soil-to-atmosphere CO2 flux, commonly though imprecisely termed soil respiration (RS ), is one of the largest carbon fluxes in the Earth system. An increasing number of high-frequency RS measurements (typically, from an automated system with hourly sampling) have been made over the last two decades; an increasing number of methane measurements are being made with such systems as well. Such high frequency data are an invaluable resource for understanding GHG fluxes, but lack a central database or repository. Here we describe the lightweight, open-source COSORE (COntinuous SOil REspiration) database and software, that focuses on automated, continuous and long-term GHG flux datasets, and is intended to serve as a community resource for earth sciences, climate change syntheses and model evaluation. Contributed datasets are mapped to a single, consistent standard, with metadata on contributors, geographic location, measurement conditions and ancillary data. The design emphasizes the importance of reproducibility, scientific transparency and open access to data. While being oriented towards continuously measured RS , the database design accommodates other soil-atmosphere measurements (e.g. ecosystem respiration, chamber-measured net ecosystem exchange, methane fluxes) as well as experimental treatments (heterotrophic only, etc.). We give brief examples of the types of analyses possible using this new community resource and describe its accompanying R software package.

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data.

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.

Nursing Faculty Experiences With Students' Needlestick Injuries.

BACKGROUND: Nursing students are at increased risk of needlestick injury (NSI) due to limited clinical experience and underdeveloped skills. PURPOSE: The purpose of this study was to describe faculty experiences with nursing students who sustain an NSI. METHODS: A retrospective cross-sectional survey design was used to examine nursing faculty experience with student NSIs occurring during clinical practicum experiences. RESULTS: Thirty-four percent (n = 904) of nursing faculty respondents reported having supervised at least 1 nursing student who experienced an NSI while providing care to a patient. Only 47% (n = 1112) of faculty indicated that a student could access effective exposure management. CONCLUSIONS: Structured simulation activities in which faculty manage a student NSI would provide faculty with essential NSI exposure management experience. Integrating blood-borne pathogen exposure management simulation into faculty development activities would bring a level of realism to the training that a lecture or written policy cannot provide.

Underreporting of Bloodborne Pathogen Exposures in Nursing Students.

BACKGROUND: Although nursing students perform many of the same procedures as licensed nurses, students are less skillful when handling sharps and are at higher risk of injury. Low rates of bloodborne pathogen (BBP) exposure reporting are described among students in all health care disciplines. PURPOSE: This study describes reporting behaviors of undergraduate nursing students who experienced a needlestick injury during a clinical practicum experience. METHODS: This study implemented a retrospective survey design to query the BBP exposure experience of nursing students in prelicensure nursing programs. RESULTS: Of the 4140 survey responses, 6.6% (n = 274) of respondents sustained a percutaneous BBP exposure during a clinical practicum experience, and 52% (n = 127) of these exposures were not reported. Reasons for nonreporting included fear the student would "get in trouble," that the incident would affect the student's clinical grade, and concern about being perceived as lacking clinical skill. CONCLUSIONS: Bridging communication gaps between students and faculty is essential to ensure that students report BBP exposures to permit access to timely triage and exposure management.

Aversive state processing in the posterior insular cortex.

Triggering behavioral adaptation upon the detection of adversity is crucial for survival. The insular cortex has been suggested to process emotions and homeostatic signals, but how the insular cortex detects internal states and mediates behavioral adaptation is poorly understood. By combining data from fiber photometry, optogenetics, awake two-photon calcium imaging and comprehensive whole-brain viral tracings, we here uncover a role for the posterior insula in processing aversive sensory stimuli and emotional and bodily states, as well as in exerting prominent top-down modulation of ongoing behaviors in mice. By employing projection-specific optogenetics, we describe an insula-to-central amygdala pathway to mediate anxiety-related behaviors, while an independent nucleus accumbens-projecting pathway regulates feeding upon changes in bodily state. Together, our data support a model in which the posterior insular cortex can shift behavioral strategies upon the detection of aversive internal states, providing a new entry point to understand how alterations in insula circuitry may contribute to neuropsychiatric conditions.

Diglycolic acid induces HepG2/C3A liver cell toxicity in vitro.

Carboxymethyl starches are added to food products for thickening or tablet binding/filling purposes. Although they lack toxicity, their synthesis creates the chemical byproduct diglycolic acid (DGA), which is difficult to eliminate and whose toxicity is in question. A rare case of an accidental direct exposure to extremely high concentrations of DGA in a person revealed that DGA has the potential to be toxic to several organs, with the kidneys and liver being the most affected organs. Given that DGA is present in our food supply as a chemical byproduct of carboxymethyl starch food additives, we sought to perform in vitro testing of its potential hepatotoxicity to help complement a recent in vivo rat acute dose-response study that also tested for the potential hepatotoxic effects of daily DGA ingestion by oral gavage over a period of 28 days. Using the HepG2/C3A cellular in vitro model, we tested how escalating doses of DGA exposure over 24 h could induce hepatotoxicity. Both in vitro and in vivo testing systems revealed that DGA is indeed a hepatotoxin once a certain exposure threshold is reached. The concordance of these models highlights the utility of in vitro testing to support and help predict in vivo findings.

Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo.

Diglycolic acid (DGA) is present in trace amounts in our food supply and is classified as an indirect food additive linked with the primary GRAS food additive carboxymethyl cellulose (CMC). Carboxymethyl starches are used as a filler/binder excipient in dietary supplement tablets and a thickening ingredient in many other processed foods. We sought to utilize the human proximal tubule HK-2 cell line as an in vitro cellular model system to evaluate its acute nephrotoxicity of DGA. We found that DGA was indeed toxic to HK-2 cells in all in vitro assays in our study, including a highly sensitive Luminex assay that measures levels of an in vitro biomarker of kidney-specific toxicity, Kidney Injury Molecule 1 (KIM-1). Interestingly, in vitro KIM-1 levels also correlated with in vivo KIM-1 levels in urine collected from rats treated with DGA by daily oral gavage. The use of in vitro and in vivo models towards understanding the effectiveness of an established in vitro system to predict in vivo outcomes would be particularly useful in rapidly screening compounds that are suspected to be unsafe to consumers. The merit of the HK-2 cell model in predicting human toxicity and accelerating the process of food toxicant screening would be especially important for regulatory purposes. Overall, our study not only revealed the value of HK-2 in vitro cell model for nephrotoxicity evaluation, but also uncovered some of the mechanistic aspects of the human proximal tubule injury that DGA may cause.

Assessing the effect of oral exposure to Paenibacillus alvei, a potential biocontrol agent, in male, non-pregnant, pregnant animals and the developing rat fetus.

Paenibacillus alvei, a naturally occurring soil microorganism, may be used in the control and/or elimination of human/animal pathogens present on/within produce commodities associated with human consumption. The safety of oral exposure to P. alvei in male, nulliparous females, the pregnant dam and developing fetus was assessed. Adult male and female rats received a single oral dose (gavage) of P. alvei and tissues were collected at post exposure days 0, 3 and 14. To evaluate the effect of the test organism on fetal development, sperm positive female rats received the test organism every 3 days thereafter throughout gestation. As human exposure would be no more than 1 × 103 CFU/ml the following dose levels were evaluated in both study phases: 0 CFU/ml tryptic soy broth (negative control); 1 × 108 CFU/ml; 1 × 104 CFU/ml or 1 × 102 CFU/ml. Neither sex specific dose-related toxic effects (feed or fluid consumption, body weight gain, and histopathology) nor developmental/reproductive effects including the number of implantations, fetal viability, fetal weight, fetal length and effects on ossification centers were observed. The test organism did not cross the placenta and was not found in the amniotic fluid.

28-day repeated dose response study of diglycolic acid: Renal and hepatic effects.

The acute oral toxicity of diglycolic acid (DGA) was evaluated. Groups of female rats (n = 8 rats/group) received 28 consecutive daily single doses of 0.3, 1.0, 3.0, 10.0, 30.0, 100.0 or 300.0 mg DGA/kg body weight by gastric intubation. One group of animals served as vehicle control. Tissues and blood serum were collected at necropsy on day 29. Select organs were weighed and fixed in formalin for histopathological analysis. Animals from the 300 mg/kg bw dose group were removed from the study after 5 consecutive days of treatment as a consequence of adverse treatment related effects. The animals in the remaining treatment groups survived the exposure period. No adverse clinical signs were observed throughout the exposure period in the surviving animals. No significant differences from controls were observed for feed and fluid consumption or body weight gain in the surviving animals. Lesions were observed in the kidneys, liver, stomach, intestine, thymus, spleen and bone marrow in rats from the 300 mg/kg dose group and signs of renal tubular regeneration were observed only in the 100 mg/kg dose group. These results suggest that high levels of pure DGA would need to be consumed before renal and other forms of organ toxicity are observed.

Silver acetate exposure: Effects on reproduction and post natal development.

Effects of oral silver acetate exposure were assessed in P generation and F generation post-natal day 26 rats. Male and female Sprague Dawley rats (n = 20 each) were exposed to silver acetate at 0.4, 4.0 or 40.0 mg/kg bw in their drinking water for 10 weeks prior to and during mating. Females were exposed to silver acetate throughout gestation and lactation. Clinical signs, body weight, feed and fluid consumption were recorded regularly. Decreased mean daily fluid consumption was observed in male and female animals during the 10 week pre mating period and during gestation in the 40 mg/kg bw dose group. Decreased fertility was observed in the 40 mg/kg bw dose group. Decreased feed consumption was observed across all dose groups and decreased mean daily fluid consumption was observed in the 4.0 mg/kg dose group during lactation. Decreased implant numbers, mean numbers of pups born/litter and numbers of live pups born/litter was observed in the 40 mg/kg bw dose group. Pup weight was reduced on lactation days 0, 4 and 7 (males) and 4, 7 and 21 (females) in the 4.0 mg/kg bw dose group and in males at lactation day 21 (40 mg/kg bw dose group). Runting was observed in males (Lactation Day; LD 4) and female (LD 4 and 7) animals in the 4.0 mg/kg bw dose group. Reduced postnatal-day 26 pup weight was observed in male pups in the 40 mg/kg bw dose group and female pups in the 4.0 mg/kg bw dose group.

Effects of maternal silver acetate exposure on immune biomarkers in a rodent model.

Male and female rats (26-day old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc) in drinking water for 10 weeks prior to and during mating. Sperm positive females remained within their dose groups and were exposed to AgAc during gestation and lactation. Splenic and thymic lymphocyte subsets from F1 generation PD (postnatal day) 4 and 26 pups were assessed by flow cytometry for changes in phenotypic markers. Spleens from PD4 pups had lower percentages of CD8+ lymphocytes in 4 and 40 mg/kg AgAc exposed groups and reduced Concanavalin A (Con A) response at all AgAc exposure groups. Splenic maturation increased in PD26 pups compared to PD4 pups. Con A and lipopolysaccharide (LPS) mediated splenic responses were lower in PD26 pups exposed to 40 mg/kg AgAc. Changes in PD 26 pup splenocyte phenotypic markers included lower TCR + cells at 4 and 40 mg/kg AgAc exposure and higher B cell population in the 40 mg/kg AgAc. PD26 pup splenic natural killer cell (NK) activity was higher in the 0.4 AgAc group and unchanged in 4 and 40 mg/kg AgAc groups. In conclusion, maternal exposure to AgAc had a significant impact on rat splenic development during the early lactation period.

Toxicogenomic study in rat thymus of F1 generation offspring following maternal exposure to silver ion.

Male and female rats (26-day-old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc) in drinking water for 10 weeks prior to and during mating. Sperm-positive females remained within their dose groups and were exposed to silver acetate during gestation and lactation. At postnatal day 26, the effect of silver ions on the developing F1 generation rat thymus was evaluated at the transcriptional level using whole-genome microarrays. Gene expression profiling analyses identified a dozen differentially expressed genes (DEGs) in each dose group using a loose criterion of fold change (FC) >1.5 and unadjusted p < 0.05, regardless of whether the analysis was conducted within each gender group or with both gender groups combined. No dose-dependent effect was observed on the number of DEGs. In addition, none of these genes had a false discovery rate (FDR) <0.05 after correction for multiple testing. These results in combination with the observation that thymus-to-body-weight ratios were not affected and no histopathological abnormalities were identified indicate that in utero exposure to silver ions up to 26.0 mg/kg (equivalent to 40.0 mg/kg silver acetate) did not have an adverse effect on the developing thymus.

Reproductive toxicity in rats with crystal nephropathy following high doses of oral melamine or cyanuric acid.

The industrial chemical melamine was used in 2007 and 2008 to raise the apparent protein content in pet feed and watered down milk, respectively. Because humans may be exposed to melamine via several different routes into the human diet as well as deliberate contamination, this study was designed to characterize the effect of high dose melamine or cyanuric acid oral exposure on the pregnant animal and developing fetus, including placental transfer. Clear rectangular crystals formed following a single triazine exposure which is a different morphology from the golden spherulites caused by combined exposure or the calculi formed when melamine combines with endogenous uric acid. Crystal nephropathy, regardless of cause, induces renal failure which in turn has reproductive sequelae. Specifically, melamine alone-treated dams had increased numbers of early and late fetal deaths compared to controls or cyanuric acid-treated dams. As melamine was found in the amniotic fluid, this study confirms transfer of melamine from mammalian mother to fetus and our study provides evidence that cyanuric acid also appears in the amniotic fluid if mothers are exposed to high doses.

Performance of urinary and gene expression biomarkers in detecting the nephrotoxic effects of melamine and cyanuric acid following diverse scenarios of co-exposure.

Although standard nephrotoxicity assessments primarily detect impaired renal function, KIM-1, clusterin, NGAL, osteopontin and TIMP-1 were recently identified biomarkers proposed to indicate earlier perturbations in renal integrity. The recent adulteration of infant and pet food with melamine (MEL) and structurally-related compounds revealed that co-ingestion of MEL and cyanuric acid (CYA) could form melamine-cyanurate crystals which obstruct renal tubules and induce acute renal failure. This study concurrently evaluated the ability of multiplexed urinary biomarker immunoassays and biomarker gene expression analysis to detect nephrotoxicity in F344 rats co-administered 60ppm each of MEL and CYA in feed or via gavage for 28days. The biomarkers were also evaluated for the ability to differentiate the effects of the compounds when co-administered using diverse dosing schedules (i.e., consecutive vs. staggered gavage) and dosing matrixes (i.e., feed vs. gavage). Our results illustrate the ability of both methods to detect and differentiate the severity of adverse effects in the staggered and consecutive gavage groups at much lower doses than previously observed in animals co-exposed to the compounds in feed. We also demonstrate that these urinary biomarkers outperform traditional diagnostic methods and represent a powerful, non-invasive indicator of chemical-induced nephrotoxicity prior to the onset of renal dysfunction.