Viral Threats to Fruit and Vegetable Crops in the Caribbean.

Viruses pose major global challenges to crop production as infections reduce the yield and quality of harvested products, hinder germplasm exchange, increase financial inputs, and threaten food security. Small island or archipelago habitat conditions such as those in the Caribbean are particularly susceptible as the region is characterized by high rainfall and uniform, warm temperatures throughout the year. Moreover, Caribbean islands are continuously exposed to disease risks because of their location at the intersection of transcontinental trade between North and South America and their role as central hubs for regional and global agricultural commodity trade. This review provides a summary of virus disease epidemics that originated in the Caribbean and those that were introduced and spread throughout the islands. Epidemic-associated factors that impact disease development are also discussed. Understanding virus disease epidemiology, adoption of new diagnostic technologies, implementation of biosafety protocols, and widespread acceptance of biotechnology solutions to counter the effects of cultivar susceptibility remain important challenges to the region. Effective integrated disease management requires a comprehensive approach that should include upgraded phytosanitary measures and continuous surveillance with rapid and appropriate responses.

Evaluation of a Novel Mechanical Venous Thromboembolism Compression Device in Trauma Patients: A Pilot Study.

BACKGROUND: Venous thromboembolism (VTE) is the fourth most common preventable hospital-acquired complication for hospitalized trauma patients. Mechanical prophylaxis, using sequential compression or intermittent pneumatic compression (IPC) devices, is recommended alongside pharmacologic prophylaxis for VTE prevention. However, compliance with device use is a barrier that reduces the effectiveness of mechanical prophylaxis. OBJECTIVE: This study aimed to determine whether using the Movement and Compressions (MAC) system compared with an IPC device impacts compliance with mechanical VTE prophylaxis in trauma patients. METHODS: This study used a before-and-after design with historical control at a Level II trauma center with a convenience sample of adult trauma patients admitted to the intensive care unit or acute care floor for at least 24 h. We trialed the MAC device for 2 weeks in November and December 2022 with prospective data collection. Data collection for the historical control group occurred retrospectively using patients from a point-in-time audit of IPC device compliance from August and September of 2022. RESULTS: A total of 51 patients met inclusion criteria, with 34 patients in the IPC group and 17 patients in the MAC group. The mean (SD) prophylaxis time was 17.2 h per day (4.0) in the MAC group and 7.5 h per day (8.8) in the IPC group, which was statistically significant (p < .001). CONCLUSION: Our findings suggest that the MAC device can improve compliance with mechanical prophylaxis.

First report of cucurbit yellow stunting disorder virus infecting cucurbit crops in Jamaica.

The increasing prevalence of whitefly-transmitted viruses affecting cucurbit crops has emerged as a significant concern for global cucurbit production. Two of the most widely prevalent threats in the Americas are cucurbit yellow stunting disorder virus (CYSDV) and cucurbit chlorotic yellows virus (CCYV) (Crinivirus, Closteroviridae). These viruses induce similar foliar symptoms on cucurbit crops (Mondal et al., 2023) leading to loss of photosynthetic capability and decreased yields. Cantaloupe (Cucumis melo), watermelon (Citrullus lanatus), and cucumber (Cucumis sativus) are major cucurbit crops in St. Elizabeth, Jamaica, which is the principal fruit and vegetable producing region of the country. In August 2018, foliar symptoms were observed on cantaloupe, watermelon, and cucumber plants in several commercial farms in St. Elizabeth. These symptoms, mainly on the older leaves, consisted of severe yellowing or interveinal mottle and they appeared more pronounced on cantaloupe and cucumber plants compared to watermelon. Growers noticed the production of smaller than normal fruit. Disease incidence ranged from 10 to 100% and whiteflies (Bemisia tabaci Gennadius) were observed in the fields. To identify virus(es) associated with the disease, six plants (cantaloupe [n = 3], cucumber [n = 1] and watermelon [n = 2) exhibiting symptoms were sampled from four fields for preliminary screening. Total RNA was extracted from leaf tissues as described in Tamang et al. (2021) and samples tested by a multiplex reverse transcription RT-PCR method that targeted the RNA-dependent RNA polymerase (RdRp) of the whitefly transmitted viruses, CYSDV, CCYV, squash vein yellowing virus (SqVYV), and the aphid- transmitted cucurbit aphid-borne yellows virus (CABYV) (Mondal et al. 2023). RT-PCR amplified the expected 494-bp fragment of the CYSDV RdRp gene (Mondal et al., 2023) from two symptomatic plants; one cantaloupe, one cucumber, as well as from CYSDV-infected control plants but not from healthy controls. Further testing was conducted during the June-August 2020 growing season after similar symptoms were observed on additional farms in St. Elizabeth and two regions, Manchester and Clarendon, located to the east of St. Elizabeth. Twenty-one cucurbit leaf samples (11 cantaloupe, seven watermelon and two cucumber from St. Elizabeth and one cantaloupe from Clarendon) exhibiting foliar yellowing progressing from the crown outward, and mottling were collected. Whiteflies (5) from these fields in St. Elizabeth and 20 asymptomatic weed samples were also collected and sent to the USDA-ARS laboratory at Salinas, CA. Total RNA from leaf samples was extracted as described above and tested for CYSDV, CCYV, and CABYV. Total leaf DNA was also extracted (Mondal et al. 2016) and assayed with PCR (Gilbertson 2001) to detect the presence of the whitefly-transmitted cucurbit leaf crumple virus (CuLCrV), a begomovirus, commonly found in the southeastern United States (Gadhave et al., 2018; Keinath et al., 2018). Nineteen of the 21 cucurbit samples tested positive for the presence of CYSDV by RT-PCR (Mondal et al. 2023). Of the 19 CYSDV-positive samples, 13 cantaloupe, one cucumber, and five watermelon samples were singly infected with CYSDV, and one cantaloupe sample was infected with both CYSDV and CABYV. Amplicons of the Jamaica isolate from cantaloupe were sequenced (OR399555) and a 494 nt section of the RdRp gene was found to share 100% sequence identity to the Arizona 1 isolate (EF547827.1). The presence of CYSDV, was further confirmed using a second set of primers that amplified a 394-nt portion of the CYSDV coat protein gene (Polston et al., 2008). Among the weed samples, CABYV was detected in one sample from a Leonotis nepetifolia plant (Lamiaceae) and two Cleome sp. (Capparaceae) collected from St. Elizabeth. None of the crop and weed samples tested positive for CCYV or CuLCrV. DNA from whiteflies was extracted and assayed with PCR using species specific primers (Chen et al. 2016). All whiteflies were identified as B. tabaci cryptic species MEAM1, which is widely known an efficient vector of CYSDV (Berdiales, et al. 1999). This is the first report of CYSDV in Jamaica and its first known occurrence in these hosts within the country. Further monitoring of cucurbit crops and the whitefly vector is warranted to better understand the epidemiology.

Autism and Mental Health: The Role of Occupational Therapy.

Research has indicated a high prevalence of mental health problems among autistic people, with elevated rates of depression, anxiety, and suicidality. The profession of occupational therapy has its roots in mental health and can offer a unique focus on occupation to support the mental health needs of autistic clients. In this Guest Editorial we introduce articles for this special issue of the American Journal of Occupational Therapy related to autism and mental health and use the Person-Environment-Occupation Model. The articles offer insights into how interactions among person, environment, and occupation factors affect the mental health of autistic populations and demonstrate ways that mental health can be supported through occupational engagement. Opportunities to support the mental health of autistic people include promoting engagement in meaningful activities, supporting individual strengths, and bolstering clients' sense of self and identification with their autistic identity. Future research is needed to uncover and test interventions to support autistic clients and should reflect cultural humility and participatory approaches. We chose to use identity-first language (rather than person-first language) to describe the autistic community in this Guest Editorial out of respect for common community member preferences and in accordance with recommendations for anti-ableist language use (Bottema-Beutel et al., 2021). Decisions about language for each article in this special issue were made by the respective authors.

Geolocator-tracking seabird migration and moult reveal large-scale, temperature-driven isoscapes in the NE Atlantic.

RATIONALE: By combining precision satellite-tracking with blood sampling, seabirds can be used to validate marine carbon and nitrogen isoscapes, but it is unclear whether a comparable approach using low-precision light-level geolocators (GLS) and feather sampling can be similarly effective. METHODS: Here we used GLS to identify wintering areas of northern gannets (Morus bassanus) and sampled winter grown feathers (confirmed from image analysis of non-breeding birds) to test for spatial gradients in δ13 C and δ15 N in the NE Atlantic. RESULTS: By matching winter-grown feathers with the non-breeding location of tracked birds we found latitudinal gradients in δ13 C and δ15 N in neritic waters. Moreover, isotopic patterns were best explained by sea surface temperature. Similar isotope gradients were found in fish muscle sampled at local ports. CONCLUSIONS: Our study reveals the potential of using seabird GLS and feathers to reconstruct large-scale isotopic patterns.

Introduction of a Protocol for Structured Follow-Up and Texting of Inadequate and Borderline-Positive Newborn Metabolic Screening Results.

A national protocol for structured follow-up and texting of repeat newborn bloodspot screening (NBS) sample requests was introduced. Repeat samples are needed where the initial sample is inadequate or the result borderline-positive. This protocol aimed to improve the timeliness and completeness of receipt of repeat NBS samples. Under the structured protocol, all repeat sample requests were phoned or texted to the lead maternity carer (LMC), in addition to the standard written report issued. Weekly text reminders were sent until 4 weeks or the sample was received. National data were monitored following implementation of the protocol. The proportion of repeat samples received within 10 days of request improved after the introduction of the protocol, from 35.0% in 2013 to 81.4% in 2020 (p < 0.001). The proportion of requests lost to follow-up decreased, from 4.1% in 2013 to 1.3% in 2020 (p < 0.001). A structured NBS follow-up protocol that included SMS text messaging led to an earlier and more complete receipt of repeat samples. This is likely due to practitioners receiving the request more quickly, as well as the laboratory adopting a consistent approach to repeated reminders. SMS text messages are a useful adjunctive method for screening programmes to communicate with health care providers.

In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.

Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high-throughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients.

Census data aggregation decisions can affect population-level inference in heterogeneous populations.

Conservation and population management decisions often rely on population models parameterized using census data. However, the sampling regime, precision, sample size, and methods used to collect census data are usually heterogeneous in time and space. Decisions about how to derive population-wide estimates from this patchwork of data are complicated and may bias estimated population dynamics, with important implications for subsequent management decisions.Here, we explore the impact of site selection and data aggregation decisions on pup survival estimates, and downstream estimates derived from parameterized matrix population models (MPMs), using a long-term dataset on grey seal (Halichoerus grypus) pup survival from southwestern Wales. The spatiotemporal and methodological heterogeneity of the data are fairly typical for ecological census data and it is, therefore, a good model to address this topic.Data were collected from 46 sampling locations (sites) over 25 years, and we explore the impact of data handling decisions by varying how years and sampling locations are combined to parameterize pup survival in population-level MPMs. We focus on pup survival because abundant high-quality data are available on this developmental stage.We found that survival probability was highly variable with most variation being at the site level, and poorly correlated among sampling sites. This variation could generate marked differences in predicted population dynamics depending on sampling strategy. The sample size required for a confident survival estimate also varied markedly geographically.We conclude that for populations with highly variable vital rates among sub-populations, site selection and data aggregation methods are important. In particular, including peripheral or less frequently used areas can introduce substantial variation into population estimates. This is likely to be context-dependent, but these choices, including the use of appropriate weights when summarizing across sampling areas, should be explored to ensure that management actions are successful.

CD30 and ALK combination therapy has high therapeutic potency in RANBP2-ALK-rearranged epithelioid inflammatory myofibroblastic sarcoma.

BACKGROUND: Epithelioid inflammatory myofibroblastic sarcoma (eIMS) is characterised by perinuclear ALK localisation, CD30 expression and early relapse despite crizotinib treatment. We aimed to identify therapies to prevent and/or treat ALK inhibitor resistance. METHODS: Malignant ascites, from an eIMS patient at diagnosis and following multiple relapses, were used to generate matched diagnosis and relapse xenografts. RESULTS: Xenografts were validated by confirmation of RANBP2-ALK rearrangement, perinuclear ALK localisation and CD30 expression. Although brentuximab-vedotin (BV) demonstrated single-agent activity, tumours regrew during BV therapy. BV resistance was associated with reduced CD30 expression and induction of ABCB1. BV resistance was reversed in vitro by tariquidar, but combination BV and tariquidar treatment only briefly slowed xenograft growth compared with BV alone. Combining BV with either crizotinib or ceritinib resulted in marked tumour shrinkage in both xenograft models, and resulted in prolonged tumour-free survival in the diagnosis compared with the relapse xenograft. CONCLUSIONS: CD30 is a therapeutic target in eIMS. BV efficacy is limited by the rapid emergence of resistance. Prolonged survival with combination ALK and CD30-targeted-therapy in the diagnosis model provides the rationale to trial this combination in eIMS patients at diagnosis. This combination could also be considered for other CD30-positive, ALK-rearranged malignancies.

Listening to the autistic voice: Mental health priorities to guide research and practice in autism from a stakeholder-driven project.

LAY ABSTRACT: Autistic adults commonly experience mental health conditions. However, research rarely involves autistic adults in deciding priorities for research on mental healthcare approaches that might work for them. The purpose of this article is to describe a stakeholder-driven project that involved autistic adults in co-leading and designing research about priorities to address mental health needs. Through a large online survey, two large meetings, and three face-to-face focus group discussions involving over 350 stakeholders, we identified five priorities for mental health research desired by autistic adults. These priorities and preferred outcomes should be used to guide research and practice for autistic adults.

Interventions to address health outcomes among autistic adults: A systematic review.

LAY ABSTRACT: Autistic adults have more health problems then their same-aged peers. Yet little research has been conducted that focuses on addressing these health problems. In order to guide future research, it is important to know what intervention studies have been done to improve health outcomes among autistic adults. The project team and student assistants read studies that were published between 2007 and 2018 in the online research database, PubMed. We looked for studies published in English, which were peer-reviewed and included (1) an intervention, (2) an outcome that was related to health, and (3) a study group that included autistic adults. We did not include studies that had outcomes about employment (unless there was a health outcome), studies about caregivers or caregiving, or expert opinions about interventions. Of 778 reviewed articles, 19 studies met all of the criteria above. Within these studies, two approaches were found to have emerging evidence for their use in autistic adults: cognitive behavioral interventions and mindfulness-based approaches for improved mental health outcomes. The remaining intervention approaches did not have enough articles to support their use. Many of the outcomes were about reduced symptoms of co-occurring mental health diagnoses (e.g. reduced anxiety, depression). Most of the participants in these studies were male and did not have intellectual disability. Most study participants were adults younger than 40. There are not many intervention studies that address health outcomes among autistic adults. More research is needed on interventions which are desired by the adult autism community and address preferred health outcomes such as increased quality of life or well-being.

Randomized Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Topical Daprodustat in Healthy Volunteers and in Patients With Diabetic Foot Ulcers.

Daprodustat, a small-molecule inhibitor of prolyl hydroxylases, prevents breakdown of hypoxia-inducible factor (HIF), leading to increased transcription of HIF-responsive genes. This randomized, placebo-controlled study evaluated the safety, tolerability, and pharmacokinetics of a topical formulation of daprodustat in healthy volunteers (intact skin) and in patients with diabetic foot ulcers (DFUs) following single and/or 14-day repeat-dose administration. In the diabetic patients, exploratory assessments of wound area, volume, and depth were made to qualitatively assess effectiveness. Systemic absorption via topical application was limited across doses up to 1.0% at 100 mg/cm2 for 14 days. Systemic pharmacokinetics were quantifiable in a few samples from a few patients. Because only sporadic concentrations were observed versus pharmacokinetic profiles, pharmacokinetic parameters were not determined. Wound area, depth, and volume showed consistent but weak improvements in the treatment arm; however, the variability in response and small sample size of the standard-of-care and placebo arms limited the ability to assess trends in wound healing compared with the daprodustat arm. Overall, topically applied daprodustat was well tolerated, raised no safety concerns, and provided limited to nonquantifiable systemic exposures. The healing of DFUs will need to be evaluated in studies designed to test this hypothesis over a longer treatment duration.

Discovery of renin inhibitors containing a simple aspartate binding moiety that imparts reduced P450 inhibition.

Discovery of potent renin inhibitors which contain a simplified alkylamino Asp-binding group and exhibit improved selectivity for renin over Cyp3A4 is described. Structure-function results in this series are rationalized based on analysis of selected compounds bound to renin, and the contribution of each molecular feature leading to the reduced P450 inhibition is quantified.

Screening and Management of Substance Use in Pregnancy: A Review.

Substance use during pregnancy has important implications for health care providers, policy makers, and can negatively impact a woman's health and the health of her children. Understanding trends, patterns of use and outcomes are critical to prevention campaigns, building awareness, and providing effective care. This review will discuss the current therapeutic approaches and recommendations for screening and patient management for substance use in pregnancy and during the postpartum period, and it is geared towards any care providers who care for patients or those who may care for patients who may be at risk for substance use during pregnancy.

A Randomized, Placebo- and Positive-Controlled, Single-Dose, Crossover Thorough QT/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in Healthy Subjects.

Daprodustat (GSK1278863) is a prolyl hydroxylase inhibitor in phase 3 clinical studies for the treatment of anemia associated with chronic kidney disease. This study was conducted to evaluate the effect of daprodustat on cardiac repolarization and enrolled 55 healthy adult male (29) and female (26) subjects who received single-dose 75 and 500 mg daprodustat, 400 mg moxifloxacin, and placebo. Mean placebo-corrected change from baseline QT interval for daprodustat showed no statistically significant increase. However, statistically significant decreases in the ΔΔQTcF were observed for both doses of daprodustat, reaching a lowest value of -2.74 milliseconds for 75 mg and -5.93 milliseconds for 500 mg daprodustat; this minor shortening effect is not considered clinically significant. The moxifloxacin group showed a statistically significant increase in the ΔΔQTcF value, reaching a maximal increase of 11.47 milliseconds at 4 hours. Forty subjects (73%) reported at least 1 adverse event, with the highest incidence with 500 mg daprodustat. This group had a higher incidence of gastrointestinal adverse events compared to the other treatment groups. These results suggest that 500 mg daprodustat was not well tolerated; however, daprodustat at 75 mg was generally well tolerated. No new safety concerns were identified in subjects who received 500 mg daprodustat.

Deconstructing Clinical Workflow: Identifying Teaching-Learning Principles for Barcode Electronic Medication Administration With Nursing Students.

The purpose of this quality improvement project was to better understand how to teach medication administration underpinned by an electronic medication administration record (eMAR) system used in simulated, prelicensure nursing education. Methods included a workflow and integration analysis and a detailed process mapping of both an oral and a sublingual medication administration. Procedural and curriculum development considerations related to medication administration using eMAR technology are presented for nurse educators.