Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.

Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-ß (CSF1R/CCR2/TGF-ß Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.

Hospital outcomes of acute COVID-19 infection among patients with neurological conditions: a single-center study.

Background: Coronavirus disease 2019 (COVID-19) infection has been associated with severe neurological consequences, including stroke or seizures, and less severe neurological sequelae, including headaches, dizziness, and anosmia. Earlier COVID-19 variants were associated with high morbidity and mortality; however, knowledge of the impact of neurological conditions in the setting of COVID-19 on healthcare outcomes is limited. We sought to determine the impact of acute neurological conditions and acute COVID-19 infection on inpatient hospitalization outcomes. Methods: This was a retrospective, observational study of adult patients who were admitted to a large academic medical center in the Southeastern US between April 2020 and December 2021 with acute COVID-19 infection and a neurological diagnosis. Patient demographics, medical history, neurological diagnoses, and hospitalization outcomes were obtained from the medical record. Descriptive statistics and unadjusted and adjusted logistic regression analyses were performed. Results: Of the 1,387 patients included in this study, 27% died and 23% were kept under ventilation during hospitalization. The mean +/- standard deviation (SD) age was 64.6+/-16.9 years, with 52.8% women and 30.1% identifying as Black/African American. The most common neurological conditions included ischemic stroke (35.0%), movement disorder (12.0%), and hemorrhagic stroke (10.7%). In-hospital death was most common among those with epilepsy (p = 0.024), headache (p = 0.026), and dementia (p < 0.0001) compared to individuals without those conditions. Ventilation support was given more commonly to dementia patients (p = 0.020). Age was a significant risk factor for death (p < 0.001) and hospital length of stay (LOS) for ventilation (p < 0.001), but no neurological condition was a significant factor in adjusted logistic regression analyses. Discussion: Mortality was high in this study, with more than one-quarter of patients dying in the hospital. Death was the most common among those with epilepsy, headache, or dementia, but no neurological condition increased the risk of in-hospital mortality or ventilation. Future studies would determine the long-term neurological sequelae of those discharged from the hospital with COVID-19 and a neurological condition.

The Role of Play in the Social Development of Grey Seal (Halichoerus grypus) Pups with Comparative Notes on the Harbour Seal (Phoca vitulina).

Juvenile grey seals are known to be highly social, interacting with contact behaviours interpreted as gentle play. However, minimal sociality of pups with their mothers and among weaned pups has been suggested. The present study aimed to observe the natural social interactions of pups to track the early ontogeny of their sociality. Pup behaviour at a salt marsh colony on the east coast of England was video-recorded. Pups interacted with their mothers around suckling bouts and after weaning as they gathered around pools. The records were transcribed to spreadsheets in 30 s time segments to estimate the frequency and co-occurrence of different behaviours. Mother-pup interaction comprised nosing contacts and sometimes contact play, involving one laying the head and fore-flipper over the other. Initial weaned pup encounters involved tentative nosing and defensive splashing, indicating contact shyness. However, socially orientated locomotor play, supine posturing, and exaggerated raising of fore- and hind-flippers led to reduced shyness and pups following one another towards the sea. Archive data on subadult interactions and on harbour seal behaviours were re-analysed. Gentle play-like contact between mother-pup, juvenile, and adult pairs is interpreted here as a universal mode of social bonding, underscoring the social structure of both grey and harbour seals.

Can Bees Detect Perfluorooctane Sulfonate (PFOS)?

The European honey bee (Apis mellifera) is an important crop pollinator threatened by multiple stressors, including exposure to contaminants. Perfluorooctane sulfonate (PFOS) is a persistent global contaminant that accumulates and biomagnifies in food chains and is detected in honey. Even sublethal exposure to PFOS is detrimental to bee health, but exposure routes are unclear and nothing is known about bee response (detection, avoidance, or attraction) to PFOS. Using Y-mazes, we studied the response of individual bees to PFOS-spiked sugar syrup at four concentrations, 0.02, 30, 61 and 103 µg L-1. Bee activity, choice behavior, and drink duration for unspiked and spiked sugar syrup was recorded for 10 min in the Y-maze system. Most bees (≥80%) tasted and then drank the sugar syrup solutions, including the PFOS-contaminated syrup. Only at 61 and 103 µg L-1 did bees significantly avoid drinking PFOS-spiked syrup, and only when given a choice with unspiked syrup. When the choice of consuming unspiked syrup was removed, the bees drank PFOS-spiked syrup at all the PFOS concentrations tested, and avoidance was not evident. Avoidance was not observed in any treatment at 0.02 or 30 µg L-1 PFOS, concentrations that are frequently reported in environmental waters in contaminated areas. These findings confirm that bees will access PFOS-contaminated resources at concentrations detrimental to the colony health, and provide evidence of potential exposure pathways that may threaten crop pollination services and also human health via food chain transfer in PFOS-contaminated areas. Environ Toxicol Chem 2024;43:1638-1647. © 2024 SETAC.

Impact of Beyond Fistula programming on economic, psychosocial and empowerment outcomes following female genital fistula repair: A retrospective study.

OBJECTIVE: To retrospectively assess changes in economic status, psychosocial status and empowerment among women who participated in Beyond Fistula reintegration programming following fistula repair. METHODS: We conducted a retrospective study among 100 Beyond Fistula program participants capturing sociodemographic characteristics, obstetric and fistula history, program participation, and our primary outcomes: economic status, psychosocial status, and empowerment via quantitative survey at two time points: before program participation and currently. Data were collected from November 2020 to July 2021 from 2013 to 2019 program participants. We compared outcomes across these two time points using paired t tests or McNemar's tests. RESULTS: The proportion of individuals owning property (28.0% vs. 38.0%, P = 0.006), having a current source of income (19.0% vs. 56.0%, P < 0.001), and saving or investing income (11.0% vs. 37.0%, P < 0.001) increased significantly from pre- to post-programming. We also identified statistically significant increases from pre- to post-programming in self-esteem (5.0 [IQR 4.0-5.0] vs. 5.0 [IQR 5.0-5.0], P < 0.001), reintegration (53.0 [IQR 43.0-69.0] vs. 65.0 [IQR 51.0-72.0], P < 0.001) and level of input into household economic decision making (2.0 [SD 1.0] vs. 2.3 [SD 1.0], P = 0.004). CONCLUSION: Beyond Fistula programming likely improved economic status, psychosocial status, and empowerment of participants. Post-surgical interventions incorporating a holistic approach can advance recovery through supporting psychosocial and economic wellbeing and should be offered to women undergoing genital fistula repair.

Fertility desires and sexual behaviours among women recovering from genital fistula repair in Eldoret, Kenya.

OBJECTIVES: The reproductive desire of women following genital fistula repair surgery is complex, varied and often not addressed, although it carries significant consequences. The aim of this study was to better understand the fertility desires and sexual behaviours of women who recently underwent surgical repair of a genital fistula. METHODS: This is a secondary analysis of a retrospective cohort study designed to assess the effectiveness of Beyond Fistula, a reintegration programme for women recovering from genital fistula surgery in Eldoret, Kenya. One hundred women who participated in the Beyond Fistula programme between 2013 and 2019 were interviewed in person regarding future fertility desire, current sexual behaviour and contraceptive use. RESULTS: Among the 79 reproductive-aged women included in this study, 63.3% reported no future desire for pregnancy. Those that desired another pregnancy were significantly younger (48.3% were 18-29 years old vs. 66.0% were 35 years old or more, p = 0.004), had fewer living children (70% had 0-2 children vs. 56% had 3 or more children, p < 0.001), and a lower level of food insecurity (27.6% reported no to marginal insecurity vs. 14%, p = 0.014). Current sexual activity was marginally different between women who did and did not desire future pregnancy (82.8% vs. 66.0%, p = 0.053). Of the 50 women in our study who did not desire pregnancy, 62.0% were sexually active and of these, only 38.7% were preventing pregnancy. Lack of knowledge and access to methods were most commonly cited as barriers to use. CONCLUSIONS: Many women recovering from genital fistula surgery do not desire pregnancy and are sexually active but are not using a method to prevent pregnancy. The potential for post-surgical reintegration programmes to address education and access to contraception is a vital and unmet need to promote reproductive empowerment in this population of women as they reestablish their lives.

Effectiveness and cost-effectiveness of an electronic mindfulness-based intervention to improve maternal mental health in the peripartum: study protocol for a randomised controlled trial.

BACKGROUND: Perinatal women are highly vulnerable to developing mental health issues and particularly susceptible to a recurrence of psychiatric illness. Poor mental health during the perinatal period can have long-term impacts on the physical and psychiatric health of both mother and child. A potentially useful strategy to improve women's mental health is through a mobile application teaching mindfulness, an evidence-based technique helping individuals focus on the present moment. METHODS: A mixed method, prospective randomised controlled trial. The study group comprise women aged 18 years and over, who are attending the public and private maternity clinics at Mater Mothers' Hospital. A sample of 360 prenatal women will be randomised into the intervention group (with the use of the mindfulness app) or usual care. Participants will remain in the study for 11 months and will be assessed at four timepoints for changes in postnatal depression, mother-infant bonding, and quality of life. A cost-effectiveness evaluation will also be conducted using quality-adjusted life year (QALY) calculations. A random selection of intervention participants will be invited to attend focus groups to give feedback on the mindfulness app. DISCUSSION: Previous studies have found mindfulness interventions can reduce stress, anxiety, depression, and sleep disturbances in a prenatal population. The risks of the intervention are low, but could be of significant benefit for women who are unable to attend face-to-face appointments due to geographical, financial, or time barriers; during endemic or pandemic scenarios; or due to health or mobility issues. TRIAL REGISTRATION: This study was approved by the Mater Misericordiae Human Research Ethics Committee (83,589). Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622001581752 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385107&isReview=true ). Registered on 22 Dec. 2022.

Stroke: Hospital Nursing Management Within the First 24 Hours.

Within the United States, someone will have a stroke approximately every 40 seconds. Eighty-five percent of strokes are ischemic, with 15% classified as either intracranial or subarachnoid hemorrhage. Stroke care is complex, and nurses play a critical role in identification, assessment, management, and coordination throughout the stroke continuum of care. This article will explore the nursing care of the patient with ischemic and hemorrhagic stroke during the first 24 hours.

Weathering alters the profile of trace metals and organic compounds in leachates and bioavailability extracts from microplastics of trail running shoes.

Microplastics (MPs) from rubber outsoles of trail running shoes may contribute significantly to contamination in protected areas. In the natural environment, weathering processes can damage MP molecular structure and alter the mobility of inorganic and organic compounds used as additives in rubber. In this study, we characterised changes in the surface morphology, functional groups, and thermal stability of MPs weathered on and below the soil surface over 12 weeks, and analysed inorganic and organic additives in leachates (0.01M CaCl2) and bioaccessibility extracts (ethyl acetate). Weathering conditions included UVC irradiation at 25 °C and 80% soil moisture. Microplastics on the soil surface exhibited cracking, fragmentation, and increased extractability of zinc, sulphur, titanium and fatty acids. Microplastics below the soil surface were not significantly physically or chemically altered, however zinc leachability increased following extended weathering by up to 155%. Bioaccessibility of thiol, aromatic and cyclic organic additives decreased from both surface and sub-surface MPs over the 12 week weathering period, but there was evidence of an increase in transformation by-products. Microplastic toxicity may be significantly altered by environmental conditions and MP weathering. It is critical ecotoxicological studies use weathered MPs to assess impacts on rare and endemic species found in protected spaces.

Exploring the gap between refugee-background communities' needs and existing community-based physical activity programs in Australia.

Physical activity programs run by local government, public health and not-for-profit sectors are a key public health strategy for improving rates of physical activity within local communities. However, these programs are underutilized. This is especially the case among members of refugee-background communities whose participation could have far-ranging and multilevel benefits. To explore how greater engagement among refugee-background communities with these programs could be fostered in Brisbane, Queensland, Australia, a qualitative study was undertaken from the perspectives of both community-based physical activity program providers and agencies involved in delivering services to refugee-background communities. This study involved a series of semi-structured interviews with a purposive sample of personnel from agencies that work with individuals and families from refugee-background communities and organizations that provide low-cost or no-cost physical activity programs and initiatives. Reflexive thematic analysis was used to interpret meaning from these data. Three themes relating to how participation in community-based physical activity programs could be improved among refugee-background communities were identified: improving cultural safety through intersectoral collaboration; confronting constraints imposed by the broader public health policy environment; and building capacity and empowering the community to diversify the sector. The findings highlight the importance of localized, deep-level intersectoral collaborations in bridging the gap between the health and social care needs of refugee-background communities and existing physical activity programs. However, a range of systems-produced barriers to the creation of such collaborations must be addressed to enable local actors to help mitigate and address the systemic exclusion of marginalized populations from participation in broader society.

This qualitative study explored how participation in community-based physical activity programs could be improved among refugee-background communities. To do this, community-based physical activity program providers and agencies involved in delivering services to refugee-background communities in Brisbane, Queensland, Australia, were invited to participate in a semi-structured interview. Reflexive thematic analysis was then used to identify patterns and themes within the interview data. This analysis found that the cultural safety of community-based physical activity programs needs to be improved. From participants' perspectives, a good way to do this is through genuine collaboration between services providing community-based physical activity programs and those working directly with refugee-background communities. Relatedly, however, participants experienced the broader public health policy environment as increasingly bureaucratic and market orientated, where top-down models are adopted and funding is ad hoc and insecure. This environment was identified as constraining the ability of service providers and agencies to collaborate on the level required to improve cultural safety for members of refugee-background communities. Relatedly, the analysis also identified the importance of building the capacity and empowering members of refugee-background communities for diversifying the sector and increasing the participation rates of refugee-background communities in community-based physical activity programs.

Behavior Skills Training with Zoological Staff to Increase Killer Whale Attending Behavior.

Attending is a requisite behavior for interactions between animals in zoological care and their care specialist (trainers). Head-dropping behavior (HDB) is incompatible with attending and was observed with two killer whales during whale-trainer interactions (WTI). Initial observations also noted inconsistencies in the trainers' application of shaping procedures during WTI. A three-part plan was developed to address trainers procedural fidelity, increase whale attending during WTI, and program for the behavioral generalization and maintenance of the whale-trainer dyads (dyad). First, behavior skills training (BST) was used to instruct trainers on discrete trial training (DTT). Second, the trainers' applied their acquired skill of DTT, targeting attending behavior, with their whale during WTI. Third, behavioral generalization was programed by switching the dyad pairs in an additional DTT generalization phase. The findings demonstrated a strong positive correlation between trainer DTT fidelity and whale attending. Finally, the results suggest that future assessments of behavioral management programs with zoological trainers and animals are warranted.

Improving Stroke Measure Compliance and Outcomes Through Hospital Collaboration.

Globally, national stroke registries have been shown to improve the quality of patient care and outcomes. However, registry utilization and implementation vary by country. In the United States, stroke-specific performance measures must be met to achieve and maintain stroke center certification awarded by the state or nationally accredited certifying bodies. The 2 stroke registries available in the United States are the American Heart Association Get With The Guidelines-Stroke registry, which is voluntary, and the Paul Coverdell National Acute Stroke Registry, funded competitively to states by the Centers for Disease Control and Prevention. Compliance with stroke processes of care is variable, and quality improvement initiatives among organizations have been shown to have an impact on improving stroke care delivery. However, the effectiveness of interorganizational continuous quality improvement approaches, especially among competing institutions, to improving stroke care is ambiguous, and no uniform governance for successful interhospital collaboration has been identified. The purpose of this article is to review national initiatives focused on interorganizational collaboration to improve stroke care delivery with a focus on interhospital collaboration in the United States to improve stroke performance measures specific to stroke center certification. The state of Kentucky's experience and utilization of the Institute for Healthcare Improvement Breakthrough Series model with key strategies for success will be discussed to serve as a foundation and empower novice stroke leaders in learning health systems. The models may be adapted internationally for application to stroke-specific care process improvement locally, regionally, and nationally; among organizations within the same health system or competing systems; and among organizations with funding or without funding to improve stroke performance measures.

Urinary glucocorticoids in harbour seal (Phoca vitulina) pups during rehabilitation.

The glucocorticoid (GC) hormone cortisol is often measured in seals to indicate their stress levels, although other endogenous GCs are usually overlooked. We investigated concentrations of four endogenous GCs in the urine of "orphan" harbour seal pups in rehabilitation. We hypothesised that the GC levels would be elevated if pups were socially isolated, without water access, and with low body mass. Ninety-six samples were collected from 32 pups at four different rehabilitation centres and were analysed by Ultra Performance Liquid Chromatography and Tandem Mass Spectrometry. Median urinary creatinine (Cr) concentrations of endogenous prednisolone (31.6 ng/mg/Cr) and prednisone (31.1 ng/mg/Cr) occurred in similar magnitude to cortisol (37.0 ng/mg/Cr), while median cortisone concentrations were higher (390 ng/mg/Cr). Prednisolone and prednisone concentrations were more strongly inversely related to pup growth rate and pup mass than cortisol and cortisone. Concentrations of all four GCs decreased with mass gain for pups with water access but did not decrease for pups without water; linear mixed models indicated the interaction between these trends was significant for cortisol and cortisone, but not for prednisolone or prednisone. These results indicate the potential value of measuring all four of these endogenous GC hormones in phocid seal pups.

Microplastic pollution on hiking and running trails in Australian protected environments.

Microplastics (MPs) are ubiquitous worldwide, present even in remote areas of the natural environment. Hiking and trail running are a source of MPs on recreational trails in protected environments, which are characterised by high biodiversity and natural, ecological or cultural significance. Our understanding of the risks of microplastic pollution is impeded however by a lack of information on MPs present in the soil environment in such areas. This study characterised the quantity and physicochemical characteristics of MPs in two conservation areas in south-eastern Australia: 1) the adjacent Duval Nature Reserve and Dumaresq Dam Reserve, and 2) the Washpool and Gibraltar Range National Parks. We measured atmospheric deposition over a six-month period in the Reserves, and baseline amounts of MPs on recreational trails in the Reserves and National Parks. Atmospheric deposition averaged 17.4 MPs m-2 day-1 and was dominated by fibres, comprising 84 % of MPs. Microplastics detected on trail surfaces ranged from 162.5 ± 41.6 MPs/linear metre to 168.7 ± 18.5 MPs/linear metre and exhibited a very wide range of physical and chemical characteristics. The majority of MPs on the trail surfaces comprised polyurethane, polyethylene terephthalate and polystyrene, and 47-71 % were fibres. Microplastics were attributed to clothing, footwear, litter, and diffuse sources. Minimising and preventing MP pollution, however, is complex given there are multiple direct and diffuse sources, and several factors influencing increased MP deposition and retention in the environment.

Trail running events contribute microplastic pollution to conservation and wilderness areas.

Clothing and footwear designed for trail running shed microplastics (MPs) during use. Trail running events may therefore present a significant source of MP pollution in conservation and wilderness areas. Microplastics may present long-term risks to biodiversity and endemic plant and animal species in such areas. In this study, we used a before-after-control-impact approach to quantify and characterise MP emissions from clothing and shoe outsoles during trail running events. Microplastic deposition on trail surfaces was assessed using both a controlled study and during two public trail running events in New South Wales, Australia (the Duval Dam Buster and the Washpool World Heritage Trail Race). Microplastics were present on trails after all events and included fibres and rubber fragments. Microplastic counts varied considerably depending on trail surface hardness and gradient, and clothing and footwear properties. The controlled study showed running tights (leggings) and shoes with soft rubber outsoles produced more MPs than shirts and hard rubbers. In the trail running events, abrasive wear to shoe outsoles produced an average of 0.3 ± 0.1 to 0.9 ± 0.2 MPs/linear metre/runner, and clothing produced 0.7 ± 0.3 to 2.0 ± 0.3 fibres/linear metre/runner, with fibres accounting for 63-69% of MPs. Microplastic deposition from both footwear and clothing was higher on sloped and rock trail surfaces than flat and soil surfaces. Laser Direct Infrared (LDIR) Imaging indicated the main types of MPs present on trails were polyurethane, polyethylene terephthalate and polyamide. Trail running is increasing in popularity and large-scale events may cause a rapid and significant input of MPs in protected areas. Land managers, event coordinators and outdoor apparel manufacturers could mitigate MP impacts however, by diverting foot traffic around ecologically sensitive areas, capping participant numbers, and developing abrasion resistant clothing and footwear.

Microplastic surface retention and mobility on hiking trails.

Hiking and trail running are a source of microplastic (MP) pollution on recreational trails in wilderness and conservation areas; however, the fate of MPs deposited on trails is poorly understood as MP mobility on such surfaces has not yet been examined. In this study, we simulated heavy rainfall (100 mm/h) on trail surfaces with existing MP pollution (in situ MPs) and spiked with 99 ± 2 rubber MPs (100-940 µm). Runoff was collected for 15 min and spiked and in situ MPs were quantified. Hydrological, erosional and microplastic responses were evaluated in relation to slope, bulk density, soil moisture and surface condition indicators, including amounts and types of surface cover and soil physical attributes. The MPs were largely immobile, with 85-100% of spiked MPs retained on trail surfaces. In situ MPs were detected in the trail runoff, with the majority being polyurethane, polypropylene and polyester. Microplastic movement was primarily influenced by hydrological effects, and analysis indicated the main explanatory variable was total runoff volume, followed by soil slaking. Trail sections with at least 15% herbaceous cover or a layer of loose alluvium had higher MP retention. Areas of resource accrual may be preferentially enriched, suggesting MPs from outdoor recreation may be concentrated on and adjacent to recreational trails. Microplastics deposited on trails may have long term implications for biodiversity and ecosystem functioning in wilderness and conservation areas, particularly around the trail corridor.

Breastfeeding Perceptions and Behavior Among Postpartum Women Initiating Different Hormonally Systemic Contraceptive Methods.

BACKGROUND: There continues to be controversy regarding the simultaneous encouragement of both breastfeeding and immediate postpartum contraception. RESEARCH AIM: To explore postpartum women's perspectives about breastfeeding and their breastfeeding behaviors, while using one of three different hormonally systemic contraceptive methods immediately postpartum over a 6 month period of time. METHODS: This was a retrospective, longitudinal, three group comparative, secondary analysis of a prospective cohort study (N = 471) of immediate postpartum contraception. Breastfeeding, for this study, was defined as providing any human milk to the infant. Participants who chose one of three different hormonally systemic forms of contraception immediately postpartum (a long-acting hormonal reversible contraceptive (n = 200), depot medroxyprogesterone acetate 150 mg (n = 98), or a non-hormonal method (n = 173)) were compared at hospital discharge, 6 weeks, 3 months, and 6 months postpartum. The primary outcome was any breastfeeding at 6 months. Secondary outcomes included any and exclusive breastfeeding, concerns about breastfeeding while using contraception, and reasons for breastfeeding discontinuation. RESULTS: There was no significant difference in the rate of any breastfeeding between the two hormonal and the non-hormonal contraceptive groups at 6 months postpartum (long-acting hormonal 20.1%, non-hormonal 21.7%, depot medroxyprogesterone acetate 13.9%, p = .77, 0.28, respectively). The number of participants who reported stopping breastfeeding due to decreased milk supply was not significantly different between any groups at all time points (total number who discontinued at 6 months postpartum was long-acting hormonal 24.7%, non-hormonal 25.1%, depot medroxyprogesterone acetate 19.3%, p = .30). CONCLUSIONS: Breastfeeding perspectives and behavioral outcomes over the first 6 months postpartum were not influenced by participants chosen form of immediate postpartum contraception.

Arsenic and cadmium leaching in co-contaminated agronomic soil and the influence of high rainfall and amendments.

Arsenic (As) and cadmium (Cd) co-contaminate agricultural systems worldwide and threaten water resources, food security and human health. This column leaching study examined As and Cd mobility in an acidic sandy loam Alfisol soil collected from the dry zone of Sri Lankafor four co-contaminant concentration combinations (spiked and 1 year aged As at 20 & 100 mg kg-1 with co-added Cd at 3 & 20 mg kg-1) i, and under the influence of high rainfall (RF), phosphorus fertilizer (P) and lime amendments. In almost all treatments a synergistic co-contaminant adsorption effect was evident which reduced leaching of both elements, significantly in the higher spiked soil concentration treatments. The magnitude of leaching decrease varied with treatment but was greater for As due to its weaker retention in the soil. The co-sorbing effects, evident even under RF, were attributed to electrostatic sorption interactions, the formation of ternary bridging complexes and surface precipitation at higher concentrations. Liming significantly retarded mobilisation of both elements in all treatments, whereas P enhanced As leaching but suppressed Cd leaching, and both amendments moderated co-contaminant effects. An antagonistic effect of Cd on As sorption was evident in two treatments which showed increased As leaching with added Cd: the RF low spike concentration treatment, accredited to washout of stable As-Cd soluble complexes; the P high concentration treatment considered due to P disruption of As-Cd bridging complexes. This work is important for effective risk mitigation in these widely occurring co-contaminated agronomic systems, and demonstrates a strong system effect on synergistic or antagonistic co-contaminant interactions.

Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus.

BACKGROUND: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient). METHODS: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L). RESULTS: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection. CONCLUSIONS: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.