Mechanisms underlying episodic nitrate and phosphorus leaching from poorly drained agricultural soils.

Poorly drained depressions within tile-drained croplands can have disproportionate environmental and agronomic impacts, but mechanisms controlling nutrient leaching remain poorly understood. We monitored nitrate and soluble reactive phosphorus (SRP) leaching using zero-tension soil lysimeters across a depression to upland gradient over 2 years in a corn-soybean (Zea mays L.-Glycine max [L.] Merr.) field in Iowa. We also measured stable isotopes (δ15N and δ18O) of nitrate to examine its sources and transformations. SRP concentrations peaked during winter and early spring after phosphorus (P) fertilization (mean = 3 mg P L-1), with highest values in the depression, and SRP was relatively stable thereafter (mean = 0.3 mg P L-1) irrespective of periods of high soil moisture that led to widespread iron (Fe) reduction across the field. During a near-average precipitation year, nitrate stable isotopes indicated direct leaching of fertilizer nitrate within days of application, followed by nitrification of fertilizer ammonium and several weeks of denitrification in depressional soils. Nevertheless, nitrate concentrations remained high (mean = 28 mg N L-1) in the depression despite strong isotopic evidence for denitrification (>48% N removal). During a wet year, nitrate concentrations were lower in the depression than upland and nitrate isotopes were highly variable, consistent with nearly complete nitrate removal by denitrification in the depression and significant denitrification in upland soils. We conclude that poorly drained depressional soils can potentially decrease nitrate leaching via denitrification under sustained wet conditions, but they inconsistently denitrify and are vulnerable to high nitrate and SRP losses when soils are not saturated, especially following fertilization.

Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming.

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including EXT1, B4GALT7, EXT2, EXTL3, XYLT2, NDST1, and SLC35B2, which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration-approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming.

Fluoride-related changes in the fetal cord blood proteome; a pilot study.

BACKGROUND: Fluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA. OBJECTIVE: To identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women. METHODS: The proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes. RESULTS: Pathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation. CONCLUSION: Maternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration.

Insights on agricultural nitrate leaching from soil block mesocosms.

Quantifying nitrate leaching in agricultural fields is often complicated by inability to capture all water draining through a specific area. We designed and tested undisturbed soil monoliths (termed "soil block mesocosms") to achieve complete collection of drainage. Each mesocosm measures 1.5 m × 1.5 m × 1.2 m and is enclosed by steel on the sides and bottom with a single outlet to collect drainage. We compared measurements from replicate mesocosms planted to corn (Zea mays L.) with a nearby field experiment with tile-drained plots ("drainage plots"), and with drainage from nearby watersheds from 2020 through 2022 under drought conditions. Annual mesocosm drainage volumes were 6.5-24.6 cm greater than from the drainage plots, likely because the mesocosms were isolated from the subsoil and could not store groundwater below the drain depth, whereas the drainage plots accumulated infiltration as groundwater. Thus, we obtained consistent nitrate leaching measurements from the mesocosms even when some drainage plots yielded no water. Despite drainage volume differences, mean flow-weighted nitrate concentrations were similar between mesocosms and drainage plots in 2 of 3 years. Mesocosm annual drainage volume was 8.7 cm lower to 16.7 cm higher than watershed drainage, likely due to lagged influences of groundwater. Corn yields were lower in mesocosms than drainage plots in 2020, but with irrigation, yields were similar in subsequent years. Mean 2020 surface soil moisture and temperature were similar between the mesocosms and nearby fields. Based on these comparisons, the mesocosms provide a robust method to measure nitrate leaching with lower variability than field plots.

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib.

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the etiological venom toxins in Naja nigricollis venom responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A2-inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a therapeutic strategy that may effectively prevent life-changing morbidity caused by snakebite in rural Africa.

Fluoride-related changes in the fetal cord blood proteome; a pilot study.

Background: Fluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride affects human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in Northern California with either high or low fluoride exposure, as identified by maternal serum fluoride concentrations. Objective: To identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women living in Northern California. Methods: The proteomes of 19 archived second-trimester cord blood samples representing highest and lowest serum fluoride concentrations from a cohort of 48 women living in Northern California, previously analyzed for serum, urine and amniotic fluoride concentrations, were characterized by mass spectrometry. Proteins highly correlated to maternal serum fluoride concentrations were identified, and further compared in a group of samples from women with the highest serum fluoride to the group with the lowest maternal serum fluoride concentrations. Results: Nine cord blood proteins were significantly correlated with maternal serum fluoride concentrations. Six of these proteins, including apolipoprotein B-100, delta homolog 1, coagulation factor X, mimecan, plasma kallikrein, and vasorin, were significantly decreased in the cord blood from women with the highest serum fluoride levels. Conclusion: Changes in the relative amounts of second trimester cord blood proteins included proteins associated with the development of the fetal hematopoetic system.

Potential of Synechococcus elongatus UTEX 2973 as a feedstock for sugar production during mixed aquaculture and swine wastewater bioremediation.

The demand for protein is increasing with an expanding world population and is influencing the rapid growth of fish and animal agriculture. These sectors are becoming a significant source of water pollution and need to develop environmentally sustainable techniques that are cost-effective, ideally with potential for downstream value-added production. This study investigated the potential of one of the fastest-growing cyanobacterial species, Synechococcus elongatus UTEX 2973, for bioremediation of mixed wastewater (combination of sturgeon and swine wastewater). Three different mixing ratios (25:75, 50:50, and 75:25 sturgeon:swine) were compared to find a suitable combination for the growth of S. elongatus as well as carbohydrate accumulation in biomass. The final biomass production was found to be 0.65 ± 0.03 g Dry cell Weight (DW)/L for 75%-25 %, 0.90 ± 0.004 g DW/L for 50%-50 %, and 0.71 ± 0.04 g DW/L for 25%-75 % sturgeon-swine wastewater combination. Cyanobacteria cultivated in 50%-50 % sturgeon-swine wastewater also accumulated 70 % total carbohydrate of DW, whereas 75%-25 % sturgeon-swine and 25%-75 % sturgeon-swine accumulated 53 % and 45 %, respectively. Subsequently, the S. elongatus cells were grown in a separate batch of 50%-50 % sturgeon-swine wastewater and compared with cells grown in BG11 synthetic growth media. Cultivation in BG11 resulted in higher biomass production but lower carbohydrate accumulation than 50%-50 % mixed wastewater. Final biomass production was 0.85 ± 0.08 g DW/L for BG11 and 0.65 ± 0.04 g DW/L for 50%-50 % sturgeon-swine wastewater. Total carbohydrate accumulated was 75 % and 64 % of DW for 50%-50 % sturgeon-swine mixed wastewater and BG11 growth media, respectively, where glycogen was the main carbohydrate component (90 %). The nutrient removal efficiencies of S. elongatus were 67.15 % for orthophosphate, 93.39 % for nitrate-nitrite, and 97.98 % for ammonia. This study suggested that S. elongatus is a promising candidate for enabling simultaneous bioremediation of mixed wastewater and the production of value-added biochemicals.

Is the Papez circuit the location of the elusive episodic memory engram?

All of the brain structures and white matter that make up Papez' circuit, as well as the circuit as a whole, are implicated in the literature in episodic memory formation and recall. This paper shows that Papez' circuit has the detailed structure and connectivity that is evidently required to support the episodic memory engram, and that identifying Papez' circuit as the location of the engram answers a number of long-standing questions regarding the role of medial temporal lobe structures in episodic memory. The paper then shows that the process by which the episodic memory engram may be formed is a network-wide Hebbian potentiation termed "racetrack potentiation", whose frequency corresponds to that observed in vivo in humans for memory functions. Further, by considering the microcircuits observed in the medial temporal lobe structures forming Papez' circuit, the paper establishes the neural mechanisms behind the required functions of sensory information storage and recall, pattern completion, pattern separation, and memory consolidation. The paper shows that Papez' circuit has the necessary connectivity to gather the various elements of an episodic memory occurring within Pöppel's experienced time or "quantum of experience". Finally, the paper shows how the memory engram located in Papez' circuit might be central to the formation of a duplicate engram in the cortex enabling consolidation and long-term storage of episodic memories.

Mapping the Caregiver Experience in a Canadian Province: Research Methodology for the Saskatchewan Caregiver Experience Study.

BACKGROUND: Policies and services for older adults are increasingly focused on living in the community, rather than relying on institutions. A total of 70-80% of community care for older adults is provided by family and friend caregivers. With Canada's aging population, the number of caregivers to older adults is growing. PURPOSE: The purpose of this paper is to describe the research methodology that was employed in the Saskatchewan Caregiver Experience Study. The methodology was used to map the experiences and gather perspectives of caregivers in Saskatchewan and to identify their priority support needs. METHODS: Qualitative description was the approach in this study. An online qualitative survey was administered via SurveyMonkey and distributed via Facebook and community newsletters. The survey collected caregiver demographics and asked three open-ended questions regarding: (1) the challenges that caregivers experience; (2) the positive aspects of caregiving; and (3) the support needs and priorities of Saskatchewan caregivers. A fourth question where caregivers could freely express any other experiences or perspectives was included. Content analysis was the method used for data analysis. RESULTS: 355 individuals met the inclusion criteria for this study. Participants were evenly distributed amongst urban-large, urban-small/medium, and rural settings in Saskatchewan. The average age of caregivers and care recipients were 61 and 83 respectively. CONCLUSION: This study has implications for research, practice, and policy. By gathering the full spectrum of the caregiver experience in Saskatchewan, this study can help to inform how communities, governments, and our healthcare system can best support caregivers in their role.

Machine-learning guided Venom Induced Dermonecrosis Analysis tooL: VIDAL.

Snakebite envenoming is a global public health issue that causes significant morbidity and mortality, particularly in low-income regions of the world. The clinical manifestations of envenomings vary depending on the snake's venom, with paralysis, haemorrhage, and necrosis being the most common and medically relevant effects. To assess the efficacy of antivenoms against dermonecrosis, a preclinical testing approach involves in vivo mouse models that mimic local tissue effects of cytotoxic snakebites in humans. However, current methods for assessing necrosis severity are time-consuming and susceptible to human error. To address this, we present the Venom Induced Dermonecrosis Analysis tooL (VIDAL), a machine-learning-guided image-based solution that can automatically identify dermonecrotic lesions in mice, adjust for lighting biases, scale the image, extract lesion area and discolouration, and calculate the severity of dermonecrosis. We also introduce a new unit, the dermonecrotic unit (DnU), to better capture the complexity of dermonecrosis severity. Our tool is comparable to the performance of state-of-the-art histopathological analysis, making it an accessible, accurate, and reproducible method for assessing dermonecrosis in mice. Given the urgent need to address the neglected tropical disease that is snakebite, high-throughput technologies such as VIDAL are crucial in developing and validating new and existing therapeutics for this debilitating disease.

Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms.

Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by current antivenoms. Repurposed small molecule drugs that inhibit specific snake venom toxins show considerable promise for tackling this neglected tropical disease. Using human skin cell assays as an initial model for snakebite-induced dermonecrosis, we show that the drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat, and varespladib, alone or in combination, inhibit the cytotoxicity of a broad range of medically important snake venoms. Thereafter, using preclinical mouse models of dermonecrosis, we demonstrate that the dual therapeutic combinations of DMPS or marimastat with varespladib significantly inhibit the dermonecrotic activity of geographically distinct and medically important snake venoms, even when the drug combinations are delivered one hour after envenoming. These findings strongly support the future translation of repurposed drug combinations as broad-spectrum therapeutics for preventing morbidity caused by snakebite.

Resolving the influence of lignin on soil organic matter decomposition with mechanistic models and continental-scale data.

Confidence in model estimates of soil CO2 flux depends on assumptions regarding fundamental mechanisms that control the decomposition of litter and soil organic carbon (SOC). Multiple hypotheses have been proposed to explain the role of lignin, an abundant and complex biopolymer that may limit decomposition. We tested competing mechanisms using data-model fusion with modified versions of the CN-SIM model and a 571-day laboratory incubation dataset where decomposition of litter, lignin, and SOC was measured across 80 soil samples from the National Ecological Observatory Network. We found that lignin decomposition consistently decreased over time in 65 samples, whereas in the other 15 samples, lignin decomposition subsequently increased. These "lagged-peak" samples can be predicted by low soil pH, high extractable Mn, and fungal community composition as measured by ITS PC2 (the second principal component of an ordination of fungal ITS amplicon sequences). The highest-performing model incorporated soil biogeochemical factors and daily dynamics of substrate availability (labile bulk litter:lignin) that jointly represented two hypotheses (C substrate limitation and co-metabolism) previously thought to influence lignin decomposition. In contrast, models representing either hypothesis alone were biased and underestimated cumulative decomposition. Our findings reconcile competing hypotheses of lignin decomposition and suggest the need to precisely represent the role of lignin and consider soil metal and fungal characteristics to accurately estimate decomposition in Earth-system models.

Contrasting geochemical and fungal controls on decomposition of lignin and soil carbon at continental scale.

Lignin is an abundant and complex plant polymer that may limit litter decomposition, yet lignin is sometimes a minor constituent of soil organic carbon (SOC). Accounting for diversity in soil characteristics might reconcile this apparent contradiction. Tracking decomposition of a lignin/litter mixture and SOC across different North American mineral soils using lab and field incubations, here we show that cumulative lignin decomposition varies 18-fold among soils and is strongly correlated with bulk litter decomposition, but not SOC decomposition. Climate legacy predicts decomposition in the lab, and impacts of nitrogen availability are minor compared with geochemical and microbial properties. Lignin decomposition increases with some metals and fungal taxa, whereas SOC decomposition decreases with metals and is weakly related with fungi. Decoupling of lignin and SOC decomposition and their contrasting biogeochemical drivers indicate that lignin is not necessarily a bottleneck for SOC decomposition and can explain variable contributions of lignin to SOC among ecosystems.

Extreme low-flow conditions in a dual-chamber denitrification bioreactor contribute to pollution swapping with low landscape-scale impact.

Denitrification bioreactors are an effective edge-of-field conservation practice for nitrate (NO3) reduction from subsurface drainage. However, these systems may produce other pollutants and greenhouse gases during NO3 removal. Here a dual-chamber woodchip bioreactor system experiencing extreme low-flow conditions was monitored for its spatiotemporal NO3 and total organic carbon dynamics in the drainage water. Near complete removal of NO3 was observed in both bioreactor chambers in the first two years of monitoring (2019-2020) and in the third year of monitoring in chamber A, with significant (p < 0.01) reduction of the NO3-N each year in both chambers with 8.6-11.4 mg NO3-N L-1 removed on average. Based on the NO3 removal observed, spatial monitoring of sulfate (SO4), dissolved methane (CH4), and dissolved nitrous oxide (N2O) gases was added in the third year of monitoring (2021). In 2021, chambers A and B had median hydraulic residence times (HRTs) of 64 h and 39 h, respectively, due to varying elevations of the chambers, with drought conditions making the differences more pronounced. In 2021, significant production of dissolved CH4 was observed at rates of 0.54 g CH4-C m-3 d-1 and 0.07 g CH4-C m-3 d-1 in chambers A and B, respectively. In chamber A, significant removal (p < 0.01) of SO4 (0.23 g SO4 m-3 d-1) and dissolved N2O (0.21 mg N2O-N m-2 d-1) were observed, whereas chamber B produced N2O (0.36 mg N2O-N m-2 d-1). Considering the carbon dioxide equivalents (CO2e) on an annual basis, chamber A had loads (~12,000 kg CO2e ha-1 y-1) greater than comparable poorly drained agricultural soils; however, the landscape-scale impact was small (<1 % change in CO2e) when expressed over the drainage area treated by the bioreactor. Under low-flow conditions, pollution swapping in woodchip bioreactors can be reduced at HRTs <50 h and NO3 concentrations >2 mg N L-1.

Poorly drained depressions can be hotspots of nutrient leaching from agricultural soils.

Much of the US Corn Belt has been drained with subsurface tile to improve crop production, yet poorly drained depressions often still flood intermittently, suppressing crop growth. Impacts of depressions on field-scale nutrient leaching are unclear. Poor drainage might promote denitrification and physicochemical retention of phosphorus (P), but ample availability of water and nutrients might exacerbate nutrient leaching from cropped depressions. We monitored nitrate, ammonium, and reactive P leaching across multiple depression-to-upland transects in north-central Iowa, using resin lysimeters buried and retrieved on an annual basis. Crops included conventional corn/soybean (Zea mays/Glycine max) rotations measured at fields with and without a winter rye (Secale cereale) cover crop, as well as juvenile miscanthus (Miscanthus × giganteus), a perennial grass. Leaching of nitrogen (N) and P was greater in depressions than in uplands for most transects and years. The median difference in nutrient leaching between paired depressions and uplands was 56 kg N ha-1 year-1 for nitrate (p = 0.0008), 0.6 kg N ha-1 year-1 for ammonium (p = 0.03), and 2.4 kg P ha-1 year-1 for reactive P (p = 0.006). Transects managed with a cover crop or miscanthus tended to have a smaller median difference in nitrate (but not ammonium or P) leaching between depressions and uplands. Cropped depressions may be disproportionate sources of N and P to downstream waters despite their generally poor drainage characteristics, and targeted management with cover crops or perennials might partially mitigate these impacts for N, but not necessarily for P.

Championing Dementia Education: Adapting an Effective Scottish Dementia Education Program for Canadian Acute Health Care Providers.

With increasing numbers of persons living with dementia and their higher rates of hospitalizations, it is necessary to ensure they receive appropriate and effective acute care; yet, acute care environments are often harmful for persons with dementia. There is a lack of dementia education for acute health care providers in Canada. Scotland presently delivers a dementia education program for health care providers, known as the Scottish National Dementia Champions Programme. The objective of this Policy and Practice Note is to present the collaborative work of Scottish experts and Canadian stakeholders to adapt the Dementia Champions Programme for use in Canada. This work to date includes: (a) an environmental scan of Canadian dementia education for acute health care providers; (b) key informant interviews; and, (c) findings from a two-day planning meeting. The results of this collaborative work can and are being used to inform the next steps to develop and pilot a Canadian dementia education program.

Caregivers to older adults require support: A scoping review of their priorities.

The vast majority of older adults who are chronically ill rely on informal caregivers for support. Caregivers often require additional support to facilitate their role. To the best of our knowledge, there has yet to be a collation of caregiver-identified priorities for support. Using existing research, this scoping review provides a comprehensive picture of what caregivers have indicated as priorities for support. Arksey and O'Malley's scoping review framework guides this review. We searched MEDLINE, CINAHL and PsycINFO databases on July 2, 2021. We selected databases based on their relevance to nursing, health and social science. Inclusion criteria were peer-reviewed research of any design, a sample population of caregivers to older adults (>55 years), manuscripts published in English and the priorities for caregiver support identified by caregivers themselves. We screened a total of 3591 records, and 33 articles met the inclusion criteria. These studies were from geographic settings across the globe and used various quantitative, qualitative and mixed-method study designs. In our synthesis, we quantified the identified priorities within the studies using coding and content analysis. We present the following list of caregiver-identified priorities: (1) orientation to the caregiving role; (2) self-care and respite; (3) adapting healthcare; (4) improved supports; (5) information needs; (6) access to resources; (7) financial assistance. Policymakers, healthcare professionals and non-profit organisations can use evidence from this review to guide decisions when developing support services and interventions for caregivers.