Health and development-related priorities and challenges of adolescents and young people: findings from South Africa and Kenya prior to and during COVID-19 pandemic.

Growing evidence documents the effects of the COVID-19 pandemic on adolescents in East and Southern Africa. We present and explore the longitudinal health and development-related priorities and challenges of adolescent advisors in South Africa and Kenya, including prior to, and during the COVID-19 pandemic. Findings were co-generated with adolescent advisors in the Eastern Cape Province of South Africa (n=15, ages 18-22 in 2019) and Kisumu, Kenya (n=16, ages 10-14 in 2020). Prior to COVID-19, adolescent advisors engaged in a participatory exercise to share and explore their health and development-related priorities and challenges in 2019 and 2020. During the COVID-19 pandemic in 2020 and 2021, members of the same groups shared their experiences, challenges and coping strategies in semi-structured telephone interviews (Eastern Cape: n=14, aged 19-23; Kisumu n=12, aged 11-16) and group-based remote participatory social media activities (n=27 activities with n=12 advisors, Eastern Cape). We thematically analysed COVID-19 activities, considering them alongside pre-pandemic priorities and challenges. Many of the health and development-related priorities and challenges identified prior to COVID-19 remained issues of concern during COVID-19. These included education; victimization and violence; teenage pregnancy; substance use; household tension, conflict and inadequate family and caregiver support; health and medication concerns (South Africa) and water and food shortages (Kenya). Other issues such as financial insecurity, mental health, and crime were strong themes that emerged during COVID-19, which were not directly reported as priorities prior. Although almost all of adolescent advisors' most pressing pandemic-related challenges were also priorities for them prior to COVID-19, these issues were often discussed as new, and caused by the onset of COVID-19. While demonstrating how COVID-19 has exacerbated pre-existing vulnerabilities, we also suggest that the pandemic may have brought about a new way for adolescents to make sense of, and articulate pre-existing challenges.

HIV and SRH healthcare delivery experiences of South African healthcare workers and adolescents and young people during COVID-19.

While substantial research has emerged from the frontlines of the COVID-19 pandemic, as well as from studies with adolescent populations, there has been a dearth of research focused in South Africa on the context-specific experiences of healthcare workers (HCWs) and the adolescents and young people (AYP) to whom they provide services. This article documents the experiences of provision and receipt of HIV and sexual and reproductive health (SRH) services during the COVID-19 pandemic from the perspective of South African HCWs (n = 13) and AYP (n = 41, ages 17-29). Findings highlight several barriers to accessing comprehensive HIV and SRH services during the pandemic including lockdown-related mobility restrictions (reported by HCWs), prioritisation of COVID-19 above other healthcare needs, longer health facility waiting times, poor treatment by HCWs (reported by AYP), discomfort and perceived stigma from having to queue outside health facilities, and fear of contracting COVID-19 (reported by both groups). While HCWs reported that HIV and SRH services continued to be available during the pandemic, AYP described seeking these services - such as long-acting reversible contraception, check-ups for their babies and medical refills - and being told that because they were not considered emergency cases, they should return on a different date. By capturing diverse experiences and perspectives from both groups, our findings reiterate the growing call for health system investments to strengthen the delivery of adolescent services, including investing in appropriate channels of communication between young people and their healthcare providers (for example, through adolescent peer supporters or community healthcare workers) and differentiated models of service delivery (for example, multi-month ART refills and community pick-ups). Closing the gap between the experiences and needs of adolescents and the healthcare workers who serve them may support young people and HCWs in buffering against changes brought about by the COVID-19 pandemic.

Development and Refinement of the American Occupational Therapy Association's Knowledge Translation Toolkit.

IMPORTANCE: Occupational therapy practitioners are expected to translate promising discoveries from empirical research into routine practice with their clients. However, complex barriers can influence practitioners' knowledge translation (KT) efforts, leading the American Occupational Therapy Association's Evidence-Based Practice (EBP) group to develop the KT Toolkit tailored to the perceived needs of occupational therapists and occupational therapy assistants. OBJECTIVE: To identify common barriers to implementing EBPs and potential strategies to support EBP uptake. DESIGN: Cross-sectional survey. SETTING: United States. PARTICIPANTS: Occupational therapy practitioners. OUTCOMES AND MEASURES: Data underwent descriptive and directed content analysis, the latter of which was guided by the Consolidated Framework for Implementation Research. RESULTS: Occupational therapy survey respondents (N = 818) identified common EBP implementation barriers (e.g., lack of time and resources, difficulty understanding research findings). Initial KT Toolkit content was developed to address these barriers and included resources for searching for, analyzing, and applying evidence in practice. CONCLUSIONS AND RELEVANCE: Survey findings have informed the development of the KT Toolkit, which includes resources designed to support occupational therapy practitioners' EBP implementation efforts. This KT Toolkit is available at AOTA.org and will be continuously revised and updated on an ongoing basis. What This Article Adds: Several barriers limit the extent to which occupational therapy practitioners can implement evidence with their client populations. The KT Toolkit is directly informed by practitioner input and provides resources to support practitioners in their efforts to translate knowledge into real-world practice.

Feasibility pilot of an adapted parenting program embedded within the Thai public health system.

BACKGROUND: This feasibility pilot of the Parenting for Lifelong Health for Young Children program in Thailand aimed to: 1) explore the feasibility of study evaluation approaches; 2) assess the feasibility of delivering an adapted program; 3) report indicative effects on child maltreatment and related outcomes; and 4) examine intervention content associated with key mechanisms of change perceived by caregivers and facilitators. METHOD: Sixty primary caregivers of children aged 2-9 years were recruited for an 8-week parenting program embedded within the local health system. Mixed-methods approaches included quantitative caregiver-report and observational data from standardized instruments, and qualitative data from individual and group interviews with caregivers and program facilitators. Analyses involved Wilcoxon signed-rank tests, paired t-tests, Friedman's ANOVA, and thematic analysis. RESULTS: Participants reported that most (65%) were grandparents or great-grandparents. Study retention and response rates were high, and enrolled caregivers attended an average of 93% of sessions. Primary outcomes showed caregiver-reported pre-post reductions in overall child maltreatment (d = - 0.58, p < 0.001), as well as reductions in physical (d = - 0.58, p < 0.001) and emotional abuse (d = - 0.40, p < 0.001). Combined caregiver report and observational assessments using the HOME Inventory showed reductions in abusive and harsh parenting (d = - 0.52, p < 0.001). Secondary outcomes demonstrated decreases in child neglect; dysfunctional parenting; poor child monitoring and supervision; parental sense of inefficacy; child behavior problems; daily report on child problem behavior; parent overall depression, anxiety, and stress; and attitudes supporting physical punishment and harsh discipline. There were increases in overall positive parenting, daily positive parenting behavior, as well as HOME Inventory assessments on parent-child relationships. Thematic analyses from interviews and focus group data identified six key program themes associated with strengthened parent-child relationships, reduced child behavior problems, improved attitudes and strategies toward discipline, and improved management of parental stress. CONCLUSIONS: This study represents one of few evaluations to test the feasibility of an evidence-based parenting program embedded within routine public health service delivery in a low- or middle-income country. Findings show preliminary effectiveness in reducing child maltreatment, improvements on 22 of 24 secondary outcomes, and perceived mechanisms of change that support quantitative findings. Prospects are promising for program scalability, pending randomized controlled trial results. TRIAL REGISTRATION: 11/01/2019, ClinicalTrials.gov, ID# NCT03539341 .

Unsymmetrical Bisquinolines with High Potency against P. falciparum Malaria.

Quinoline-based scaffolds have been the mainstay of antimalarial drugs, including many artemisinin combination therapies (ACTs), over the history of modern drug development. Although much progress has been made in the search for novel antimalarial scaffolds, it may be that quinolines will remain useful, especially if very potent compounds from this class are discovered. We report here the results of a structure-activity relationship (SAR) study assessing potential unsymmetrical bisquinoline antiplasmodial drug candidates using in vitro activity against intact parasites in cell culture. Many unsymmetrical bisquinolines were found to be highly potent against both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum parasites. Further work to develop such compounds could focus on minimizing toxicities in order to find suitable candidates for clinical evaluation.

ELQ-331 as a prototype for extremely durable chemoprotection against malaria.

BACKGROUND: The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and pharmacokinetic profiles after oral dosing, ELQ-331, a prodrug of the parasite mitochondrial electron transport inhibitor ELQ-300, was selected for study of pharmacokinetics and efficacy as LAI-C in mice. METHODS: Four trials were conducted in which mice were injected with a single intramuscular dose of ELQ-331 or other ELQ-300 prodrugs in sesame oil with 1.2% benzyl alcohol; the ELQ-300 content of the doses ranged from 2.5 to 30 mg/kg. Initial blood stage challenges with Plasmodium yoelii were used to establish the model, but the definitive study measure of efficacy was outcome after sporozoite challenge with a luciferase-expressing P. yoelii, assessed by whole-body live animal imaging. Snapshot determinations of plasma ELQ-300 concentration ([ELQ-300]) were made after all prodrug injections; after the highest dose of ELQ-331 (equivalent to 30 mg/kg ELQ-300), both [ELQ-331] and [ELQ-300] were measured at a series of timepoints from 6 h to 5½ months after injection. RESULTS: A single intramuscular injection of ELQ-331 outperformed four other ELQ-300 prodrugs and, at a dose equivalent to 30 mg/kg ELQ-300, protected mice against challenge with P. yoelii sporozoites for at least 4½ months. Pharmacokinetic evaluation revealed rapid and essentially complete conversion of ELQ-331 to ELQ-300, a rapidly achieved (< 6 h) and sustained (4-5 months) effective plasma ELQ-300 concentration, maximum ELQ-300 concentrations far below the estimated threshold for toxicity, and a distinctive ELQ-300 concentration versus time profile. Pharmacokinetic modeling indicates a high-capacity, slow-exchange tissue compartment which serves to accumulate and then slowly redistribute ELQ-300 into blood, and this property facilitates an extremely long period during which ELQ-300 concentration is sustained above a minimum fully-protective threshold (60-80 nM). CONCLUSIONS: Extrapolation of these results to humans predicts that ELQ-331 should be capable of meeting and far-exceeding currently published duration-of-effect goals for anti-malarial LAI-C. Furthermore, the distinctive pharmacokinetic profile of ELQ-300 after treatment with ELQ-331 may facilitate durable protection and enable protection for far longer than 3 months. These findings suggest that ELQ-331 warrants consideration as a leading prototype for LAI-C.

A systematic review of the South African work on the well-being of young people (2000-2016).

Burgeoning research on the well-being of young people in recent years has made it difficult to identify conceptual gaps in the literature. We conducted a review of South African research in this area to better understand the use and measurement of the construct, as well as factors associated with it. The search of multiple databases identified 28 studies published in academic journals between 2000 and 2016. Within this period, studies that referred to well-being and its related subjective components varied significantly in terms of how they defined and operationalised these constructs, resulting in a fragmented body of work. The review highlights the need for a coherent research agenda in this area given the centrality of well-being research in promoting optimal outcomes in young people. Recommendations for strengthening South African research in this area are provided.

Tuberculosis Incidence Among Populations at High Risk in California, Florida, New York, and Texas, 2011-2015.

OBJECTIVES: To illustrate the magnitude of between-state heterogeneities in tuberculosis (TB) incidence among US populations at high risk for TB that may help guide state-specific strategies for TB elimination. METHODS: We used data from the National Tuberculosis Surveillance System and other public sources from 2011 to 2015 to calculate TB incidence in every US state among people who were non-US-born, had diabetes, or were HIV-positive, homeless, or incarcerated. We then estimated the proportion of TB cases that reflected the difference between each state's reported risk factor-specific TB incidence and the lowest incidence achieved among 4 states (California, Florida, New York, Texas). We reported these differences for the 4 states and also calculated and aggregated across all 50 states to quantify the total percentage of TB cases nationally that reflected between-state differences in risk factor-specific TB incidence. RESULTS: On average, 24% of recent TB incidence among high-risk US populations reflected heterogeneity at the state level. The populations that accounted for the greatest percentage of heterogeneity-reflective cases were non-US-born individuals (51%) and patients with diabetes (24%). CONCLUSIONS: State-level differences in TB incidence among key populations provide clues for targeting state-level interventions.

Simplified Reversed Chloroquines To Overcome Malaria Resistance to Quinoline-Based Drugs.

Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data from in vitro heme binding and ß-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against Plasmodium falciparum similar to those of CQ, although other mechanisms of action may be relevant to their activities.

Continuous Retention and Viral Suppression Provide Further Insights Into the HIV Care Continuum Compared to the Cross-sectional HIV Care Cascade.

BACKGROUND: The human immunodeficiency virus (HIV) care continuum has become an important tool for evaluating HIV care. Current depictions of the care continuum are often cross-sectional and evaluate retention and viral suppression (VS) in a single year, yet the National HIV/AIDS Strategy calls for programs with long-lasting outcomes. METHODS: Retrospective chart review of HIV-infected patients enrolled in a large, urban clinic in 2010 followed longitudinally for 36 months. McNemar comparisons and logistic regression analyses were conducted to evaluate covariate association with continuous retention and VS. Generalized estimating equation log-linear models were used to integrate time into the model. RESULTS: Among 655 patients (77% male, 83% black, 54% men who have sex with men (MSM), 78% uninsured) continuous retention/VS at 12 months (84%/64%), 24 months (60%/48%), and 36 months (49%/39%) showed significant attrition (P < .0001) over time. Continuous retention was associated with prevalent VS at the end of 36 months (adjusted prevalence ratio 3.12; 95% confidence interval [CI], 2.40, 4.07). 12-month retention for black (84%) and nonblack (85%) patients was equivalent, yet fewer blacks (46%) than nonblacks (63%) achieved 36-month continuous retention due to a significant interaction between race and time (aOR 0.75, 95% CI, .59, .95). CONCLUSIONS: Continuous retention is a critically important measure of long-term success in HIV treatment and the crucial component of successful treatment-as-prevention but is infrequently evaluated. Single cross-sections may overestimate successful retention and virologic outcomes. A longitudinal HIV care continuum provides greater insight into long-term outcomes and exposes disparities not evident with traditional cross-sectional care continua.

Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria.

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV-resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV.

Interrogating the Tailoring Steps of Pactamycin Biosynthesis and Accessing New Pactamycin Analogues.

Pactamycin is a bacteria-derived aminocyclitol antibiotic with a wide-range of biological activity. Its chemical structure and potent biological activities have made it an interesting lead compound for drug discovery and development. Despite its unusual chemical structure, many aspects of its formation in nature remain elusive. Using a combination of genetic inactivation and metabolic analysis, we investigated the tailoring processes of pactamycin biosynthesis in Streptomyces pactum. The results provide insights into the sequence of events during the tailoring steps of pactamycin biosynthesis and explain the unusual production of various pactamycin analogues by S. pactum mutants. We also identified two new pactamycin analogues that have better selectivity indexes than pactamycin against malarial parasites.

ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.

ELQ-300 is a preclinical candidate that targets the liver and blood stages of Plasmodium falciparum, as well as the forms that are crucial to transmission of disease: gametocytes, zygotes, and ookinetes. A significant obstacle to the clinical development of ELQ-300 is related to its physicochemical properties. Its relatively poor aqueous solubility and high crystallinity limit absorption to the degree that only low blood concentrations can be achieved following oral dosing. While these low blood concentrations are sufficient for therapy, the levels are too low to establish an acceptable safety margin required by regulatory agencies for clinical development. One way to address the challenging physicochemical properties of ELQ-300 is through the development of prodrugs. Here, we profile ELQ-337, a bioreversible O-linked carbonate ester prodrug of the parent molecule. At the molar equivalent dose of 3 mg/kg of body weight, the delivery of ELQ-300 from ELQ-337 is enhanced by 3- to 4-fold, reaching a maximum concentration of drug in serum (C max) of 5.9 µM by 6 h after oral administration, and unlike ELQ-300 at any dose, ELQ-337 provides single-dose cures of patent malaria infections in mice at low-single-digit milligram per kilogram doses. Our findings show that the prodrug strategy represents a viable approach to overcome the physicochemical limitations of ELQ-300 to deliver the active drug to the bloodstream at concentrations sufficient for safety and toxicology studies, as well as achieving single-dose cures.

Depsipeptide companeramides from a Panamanian marine cyanobacterium associated with the coibamide producer.

Two new cyclic depsipeptides, companeramides A (1) and B (2), have been isolated from the phylogenetically characterized cyanobacterial collection that yielded the previously reported cancer cell toxin coibamide A (collected from Coiba Island, Panama). The planar structures of the companeramides, which contain 3-amino-2-methyl-7-octynoic acid (Amoya), hydroxy isovaleric acid (Hiva), and eight α-amino acid units, were established by NMR spectroscopy and mass spectrometry. The absolute configuration of each companeramide was assigned using a combination of Marfey's methodology and chiral-phase HPLC analysis of complete and partial hydrolysis products compared to commercial and synthesized standards. Companeramides A (1) and B (2) showed high nanomolar in vitro antiplasmodial activity but were not overtly cytotoxic to four human cancer cell lines at the doses tested.

Discovery of dual function acridones as a new antimalarial chemotype.

Preventing and delaying the emergence of drug resistance is an essential goal of antimalarial drug development. Monotherapy and highly mutable drug targets have each facilitated resistance, and both are undesirable in effective long-term strategies against multi-drug-resistant malaria. Haem remains an immutable and vulnerable target, because it is not parasite-encoded and its detoxification during haemoglobin degradation, critical to parasite survival, can be subverted by drug-haem interaction as in the case of quinolines and many other drugs. Here we describe a new antimalarial chemotype that combines the haem-targeting character of acridones, together with a chemosensitizing component that counteracts resistance to quinoline antimalarial drugs. Beyond the essential intrinsic characteristics common to deserving candidate antimalarials (high potency in vitro against pan-sensitive and multi-drug-resistant Plasmodium falciparum, efficacy and safety in vivo after oral administration, inexpensive synthesis and favourable physicochemical properties), our initial lead, T3.5 (3-chloro-6-(2-diethylamino-ethoxy)-10-(2-diethylamino-ethyl)-acridone), demonstrates unique synergistic properties. In addition to 'verapamil-like' chemosensitization to chloroquine and amodiaquine against quinoline-resistant parasites, T3.5 also results in an apparently mechanistically distinct synergism with quinine and with piperaquine. This synergy, evident in both quinoline-sensitive and quinoline-resistant parasites, has been demonstrated both in vitro and in vivo. In summary, this innovative acridone design merges intrinsic potency and resistance-counteracting functions in one molecule, and represents a new strategy to expand, enhance and sustain effective antimalarial drug combinations.

Prevalence and indicators of viral suppression among persons with diagnosed HIV infection retained in care - Georgia, 2010.

Advances in treatment have led to dramatic improvements in the health of persons infected with human immunodeficiency virus (HIV). Moreover, treatment can reduce HIV transmission because suppressed levels of circulating virus makes HIV-infected persons less infectious. Until recently, antiretroviral therapy (ART) was recommended only for HIV patients with advanced disease (stages 2 and 3), and was optional for patients with early disease (stage 1). In March 2012, national HIV treatment guidelines were changed to recommend ART at all disease stages. To establish a baseline for care and treatment outcomes among persons with HIV, the Georgia Department of Public Health (DPH) examined whether viral suppression among HIV patients in Georgia varied by disease stage at diagnosis before implementation of the new guidelines. Disease stage at diagnosis was assessed as an indicator of viral suppression several months after diagnosis, adjusting for age, sex, and race/ethnicity among patients who were reported to DPH with HIV infections newly diagnosed during 2010 and retained in care. This report describes the results of that analysis, which indicated that disease stage at diagnosis was a significant indicator of viral suppression; viral suppression was significantly less frequent among persons with earlier disease stage at diagnosis. Compared with viral suppression among 80.5% of persons with stage 3 HIV disease, only 72.3% with stage 2 disease (prevalence ratio [PR] = 0.9; 95% confidence interval [CI] = 0.8-1.0) and 64.5% with stage 1 disease (PR = 0.8; CI = 0.7-0.9) met criteria for viral suppression, likely resulting from lack of initiating treatment or inadequate adherence to treatment regimens, as suggested in previous studies. These data can serve as a baseline to determine the impact of the guideline change in the future, and can be used to emphasize the importance of implementing the guidelines by expanding treatment to persons at all disease stages to reach the goal of viral suppression for all persons with HIV, thus closing the gap in viral suppression among persons diagnosed at disease stages 1 and 2. Health-care providers and community-based organizations should inform patients of the recommendation for ART initiation at all disease stages.

Stereospecific synthesis of 23-hydroxyundecylprodiginines and analogues and conversion to antimalarial premarineosins via a Rieske oxygenase catalyzed bicyclization.

Facile and highly efficient synthetic routes for the synthesis of (S)- and (R)-23-hydroxyundecylprodiginines ((23S)-2, and (23R)-2), 23-ketoundecylprodiginine (3), and deuterium-labeled 23-hydroxyundecylprodiginine ([23-d]-2) have been developed. We demonstrated a novel Rieske oxygenase MarG catalyzed stereoselective bicyclization of (23S)-2 to premarineosin A (4), a key step in the tailoring process of the biosynthesis of marineosins, using a marG heterologous expression system. The synthesis of various A-C-ring functionalized prodiginines 32-41 was achieved to investigate the substrate promiscuity of MarG. The two analogues 32 and 33 exhibit antimalarial and cytotoxic activities stronger than those of the marineosin intermediate 2, against Plasmodium falciparum strains (CQ(S)-D6, CQ(R)-Dd2, and 7G8) and hepatocellular HepG2 cancer cell line, respectively. Feeding of 34-36 to Streptomyces venezuelae expressing marG led to production of novel premarineosins, paving a way for the production of marineosin analogues via a combinatorial synthetic/biosynthetic approach. This study presents the first example of oxidative bicyclization mediated by a Rieske oxygenase.

Japanese Yew (Taxus) poisoning of wild ungulates in Utah during the winter of 2022-2023.

Taxus is a genus of coniferous shrubs and trees, commonly known as the yews, in the family Taxaceae. All species of yew contain taxine alkaloids, which are ascribed as the toxic principles. Anecdotally, free ranging ruminants such as antelope, deer, elk, and moose have been regarded as tolerant to yew. Herein several cases of intoxication of deer, elk, and moose by yew from the state of Utah in the winter of 2022-2023 are documented. Ingestion of yew was documented by three means among the poisoned cervids; plant fragments consistent with yew were visually observed in the rumen contents, chemical analysis, and subsequent detection of the taxines from rumen and liver contents, and identification of exact sequence variants identified as Taxus species from DNA metabarcoding. Undoubtedly, the record snowfall in Utah during the winter of 2022-2023 contributed to these poisonings.