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Glioblastoma accounts for nearly half of all primary malignant brain tumors in adults, and despite an aggressive standard of care, including excisional surgery and adjuvant chemoradiation, recurrence remains universal, with an overall median survival of 14.6 months. Recent work has revealed the importance of passenger mutations as critical mediators of metabolic adaptation in cancer progression. In our previous work, we identified a role for the epigenetic modifier ID-1 in temozolomide resistance in glioblastoma. Here, we show that ID-1-mediated glioblastoma tumourigenesis is accompanied by upregulation of one-carbon (1-C) mediated de novo purine synthesis. ID-1 knockout results in a significant reduction in the expression of 1-C metabolism and purine synthesis enzymes. Analysis of glioblastoma surgical specimens at initial presentation and recurrence reveals that 1-C purine synthesis metabolic enzymes are enriched in recurrent glioblastoma and that their expression correlates with a shorter time to tumor recurrence. Further, we show that the 1-C metabolic phenotype underlies proliferative capacity and temozolomide resistance in glioblastoma cells. Supplementation with exogenous purines restores proliferation in ID-1-deficient cells, while inhibition of purine synthesis with AICAR sensitizes temozolomide-resistant glioblastoma cells to temozolomide chemotherapy. Our data suggest that the metabolic phenotype observed in treatment-resistant glioma cells is a potential therapeutic target in glioblastoma., (© 2024. The Author(s).)

Medical student-led walk and talk programs, such as Walk with a Future Doc (WWAFD) , provide a means for the medical community and community at-large to interact in a non-clinical setting. This environment can increase attendance accountability, enhance patient-provider relationships, and allow medical professionals to be leading examples of healthy, active living. We demonstrate the positive interest for this program, rationale of participants for joining, and the feasibility of its setup. As one of the only WWAFD programs in Canada, we encourage other medical schools to implement this program to promote continuity of hands-on, community-engaged learning amongst their students., Competing Interests: The authors have no conflicts of interest to report., (© 2024 Wilson, Theou, O’Brien; licensee Synergies Partners.)

The northern giant hornet Vespa mandarinia (NGH) is a voracious predator of other insect species, including honey bees. NGH's native range spans subtropical and temperate regions across much of east and southeast Asia and, in 2019, exotic populations of the species were discovered in North America. Despite this broad range and invasive potential, investigation of the population genomic structure of NGH across its native and introduced ranges has thus far been limited to a small number of mitochondrial samples. Here, we present analyses of genomic data from NGH individuals collected across the species' native range and from exotic individuals collected in North America. We provide the first survey of whole-genome population variation for any hornet species, covering this species' native and invasive ranges, and in doing so confirm likely origins in Japan and South Korea for the two introductions. We additionally show that, while this introduced population exhibited strongly elevated levels of inbreeding, these signatures of inbreeding are also present in some long-standing native populations, which may indicate that inbreeding depression alone is insufficient to prevent the persistence of NGH populations. As well as highlighting the importance of ongoing monitoring and eradication efforts to limit the spread of this species outside of its natural range, our data will serve as a foundational database for future genomic studies into introduced hornet populations., (© 2024. The Author(s).)

The aromatic compound ( E )-anethol is widely used in the flavor, fragrance, and medicinal industries. This compound is commonly produced through steam distillation of fennel, star anise, and anise seed. Given the cost of production, these natural and authentic essential oils are commonly adulterated with lower-cost natural materials or synthetic alternatives. The current study investigates essential oil profiles (gas chromatography/mass spectrometry) and stable isotope ratios (gas chromatography/isotope ratio mass spectrometry) of the abundant compound ( E )-anethol in both authentic reference standards ( n = 15) and commercially available samples ( n = 30). This multifaceted analytical approach establishes techniques for ensuring the authenticity of essential oil sources of ( E )-anethol and was then used to evaluate the current essential oil market sources of ( E )-anethol. These findings report that adulteration of ( E )-anethol-containing natural products takes various forms, and a multifaceted analytical approach is recommended for authentication. Of the commercial samples analyzed for this report, 27% were adulterated.

Background: Splanchnic vein thrombosis (SVT) is a well-recognized complication of acute pancreatitis. The question of whether or not to treat SVT with systemic therapeutic anticoagulation (STA) remains to be seen. The universal use of anticoagulation may lead to an increased risk of bleeding complications associated with acute pancreatitis. Literature on this subject is sparse and there is no clear guideline on how to treat SVT. Our research demonstrates local practice where therapeutic anticoagulation in SVT varies., Methods: A retrospective review of patients presenting with acute pancreatitis admitted over a five-year period to a single tertiary hospital with splanchnic vein thrombosis was performed., Results: Of the 1408 patients admitted with acute pancreatitis, 42 were diagnosed with splanchnic vein thrombosis, with a male dominance of 34 (81%). A total of 25 patients received anticoagulation. The use of anticoagulation was dependent on the location of the thrombus, P < 0.01. Anticoagulation use was most common in cases of combination mesenteric, splenic, and portal vein thrombus (100%), isolated mesenteric vein (100%), isolated portal vein (89%), combination portal and splenic vein (87%), and combination mesenteric and splenic vein (75%). The rate of anticoagulation use was lowest in isolated splenic vein thrombus (23%)., Conclusion: The early commencement of STA in patients with acute pancreatitis and triple-vessel SVT or with portal vein involvement is supported by our data. Isolated splenic vein thrombus does not require systemic therapy. Further research is needed to establish a clear clinical guideline., (© 2023 Royal Australasian College of Surgeons.)

Objective: Interstitial lung disease (ILD) is a leading cause of mortality in rheumatoid arthritis (RA), particularly in those with the usual interstitial pneumonia subtype (RA-UIP). Serum antibodies to peptidylarginine deiminase type 4 (anti-PAD4), particularly a subset that cross-react with PAD3 (PAD3/4XR), have been associated with imaging evidence of ILD. We aimed to determine the specificity of anti-PAD4 antibodies in RA-ILD and to examine associations with markers of ILD severity., Methods: 48 RA-ILD and 31 idiopathic pulmonary fibrosis (IPF) patients were identified from the National Jewish Health Biobank. RA-ILD subtype was defined by imaging pattern on high-resolution chest computed tomography (CT), and serum was tested for anti-PAD4 and anti-PAD3/4XR antibodies. Antibody prevalence, measures of ILD severity (% predicted forced vital capacity, FVC; % predicted diffusion capacity carbon monoxide, DLCO; quantitative CT fibrosis) and mortality were compared between groups., Results: Anti-PAD4 antibodies were present in 9/48 (19%) subjects with RA-ILD and no subjects with IPF. Within RA-ILD, anti-PAD4 antibodies were found almost exclusively in RA-UIP (89%). Within RA-UIP subjects, % predicted FVC was higher in anti-PAD4+ subjects, and this finding was most strongly associated with anti-PAD3/4XR antibodies. In addition, quantitative CT fibrosis score was lower in anti-PAD4+ RA-UIP subjects, including those with mono-reactive anti-PAD4 antibodies and anti-PAD3/4XR antibodies. Anti-PAD4+ RA-UIP subjects also exhibited decreased mortality., Conclusions: We demonstrate the presence of serum anti-PAD4 antibodies in a subset of patients with RA-UIP that were notably associated with better lung function, less fibrosis and decreased mortality., Competing Interests: Declaration of Competing Interest The authors disclose the following potential conflicts: ED and MKD have received research support from Pfizer Inc. on studies related to RA-related autoimmunity and ILD. ED has received research support from Bristol Myers Squibb and Celgene. SMH is an author on licensed patent no. 10,706,533, entitled “Systems and methods for automatic detection and quantification using dynamic feature classification”. ED is an author on licensed patent no. 8,975,033, entitled "Human autoantibodies specific for pad3 which are cross-reactive with pad4 and their use in the diagnosis and treatment of rheumatoid arthritis and related diseases”. All other authors have declared that no conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Screening for cognitive impairment following ICU discharge is recommended but not part of routine care. We sought to understand older adults' perspectives on screening for cognitive impairment following an ICU admission to inform the design and delivery of a cognitive screening intervention., Design: Qualitative study using semi-structured interviews., Subjects: Adults 60 years and older within 3 months of discharge from an ICU in an academic health system., Interventions: Interviews were conducted via telephone, audio recorded and transcribed verbatim. All transcripts were coded in duplicate. Discrepancies were resolved by consensus. Codes were organized into themes and subthemes inductively., Measurements and Main Results: We completed 22 interviews. The mean age of participants was 71 ± 6 years, 14 (63.6%) were men, 16 (72.7%) were White, and 6 (27.3%) were Black. Thematic analysis was organized around four themes: 1) receptivity to screening, 2) communication preferences, 3) information needs, and 4) provider involvement. Most participants were receptive to cognitive screening; this was influenced by trust in their providers and prior experience with cognitive screening and impairment. Participants preferred simple, direct, compassionate communication. They wanted to understand the screening procedure, the rationale for screening, and expectations for recovery. Participants desired input from their primary care provider to have their cognitive screening results placed in the context of their overall health, because they had a trusted relationship, and for convenience., Conclusions: Participants demonstrated limited understanding of and exposure to cognitive screening but see it as potentially beneficial following an ICU stay. Providers should use simple, straightforward language and place emphasis on expectations. Resources may be needed to assist primary care providers with capacity to provide cognitive screening and interpret results for ICU survivors. Implementation strategies can include educational materials for clinicians and patients on rationale for screening and recovery expectations., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Two species within the Lamiaceae (mint) family, Agastache urticifolia and Monardella odoratissima , are aromatic plants that are native to the Intermountain Region (USA). Essential oil produced through steam distillation was examined to establish the essential oil yield and both the achiral and chiral aromatic profiles of both plant species. The resulting essential oils were analyzed by GC/MS, GC/FID, and MRR (molecular rotational resonance). For A. urticifolia and M. odoratissima , achiral essential oil profiles were largely composed of limonene (71.0%, 27.7%), trans -β-ocimene (3.6%, 6.9%), and pulegone (15.9%, 4.3%), respectively. Between the two species, eight chiral pairs were analyzed and, interestingly, the dominant enantiomer (calculated as ee%) of limonene and pulegone switched between the two species. Where enantiopure standards were not commercially available, MRR was used as a reliable analytical technique for chiral analysis. This study verifies the achiral profile for A. urticifolia and, for the first time to the authors' knowledge, establishes the achiral profile for M. odoratissima and chiral profile for both species. Additionally, this study confirms the utility and practicality of using MRR for determining chiral profiles in essential oils.

Osmorhiza occidentalis Torr. is an essential-oil-bearing plant in the Apiaceae family. Volatile oil was produced through steam distillation ( n = 3) of the above ground plant parts and was analyzed by gas chromatography (GC/FID, GC/MS), and gas chromatography/isotope ratio mass spectrometry (GC/IRMS) to establish the essential oil composition and stable isotope profile. The resulting essential oils were found to be comprised of 33 volatile compounds. Prominent volatile compounds include methyl chavicol (avg. 61.6%), ( Z )-β-ocimene (avg. 14.7%), sabinene (avg. 10.5%), and γ-terpinene (avg. 2.8%). Stable isotope values were determined for prominent volatile compounds, including methyl chavicol, ( Z )-β-ocimene, sabinene, and γ-terpinene. Values for δ 2 H range from -393.479 (avg. sabinene) to -171.516 (avg. methyl chavicol). Those for δ 13 C range from -35.957 (avg. methyl chavicol) to -30.820 (avg. ( Z )-β-ocimene). The essential oil yield was 0.12% ( w/w ). The current study establishes for the first time, to the best knowledge of the authors, the essential oil yield, essential oil composition, and stable isotope profile of prominent volatile compounds extracted from the above-ground portions of O. occidentalis . These results provide insight into the volatile chemical composition produced by the plant and provide fundamental data for substantiation of ethnobotanical applications.

Background: Kangaroo-related motor vehicle collisions are common but there is limited literature on this topic. Drivers confronted by kangaroos may choose to swerve or to directly collide with the kangaroo. The effect of these differing crash mechanisms, along with the effect of vehicle type or time of day, has not yet been reported., Methods: A retrospective cohort study was performed, examining patients admitted to our tertiary trauma centre for kangaroo-related motor vehicle collisions between 2000 and 2020. Data on patient demographics, crash characteristics, and hospital stay were collected and analysed., Results: A total of 366 patients were included and were predominantly male (76%) with an median age of 40. Swerve crashes were more common (59%) than direct impact and swerving was a statistically significant predictor of reduced injury severity score on multivariable analysis (other significant factors were female sex and no rollover). Motor vehicle crashes and motorbike crashes had differing crash characteristics. Motor vehicle crashes were more likely the result of swerving, and swerving was less likely to cause ejection or require extrication but more likely to cause rollover. Motorbike crashes however, were more likely the result of head on collision and riders were more likely to be ejected from the vehicle, require extrication, or be involved in a rollover. In terms of time of day, there were more crashes at dawn and there was a trend towards higher injury severity score and length of stay for night-time crashes., Conclusion: For kangaroo-related motor vehicle crashes, predictors of increased injury severity score on multivariable analysis were male sex, direct impact, and rollover. Motorbikes and motor vehicles had differing crash mechanisms and characteristics, as did night-time crashes when compared to daytime or twilight crashes., Level of Evidence: IV, prognostic., (Copyright © 2022. Published by Elsevier Ltd.)

Vascular mineralization is a hallmark of enzootic calcinosis. Histopathological, ultrastructural, and immunohistochemical investigations were performed on the external carotid arteries of seven sheep naturally poisoned by Nierembergia veitchii . Histologically, moderate to marked hyperplasia of the tunica intima was observed without mineralization. The tunica media exhibited mild to severe mineralization and osteochondroid metaplasia. Sheep with enzootic calcinosis showed arterial overexpression of osteopontin and tissue-nonspecific alkaline phosphatase and immunolabeling for osteonectin and osteocalcin in both intima and media layers of the tested arteries. The main ultrastructural finding in the tunica media was a marked phenotypic change of vascular smooth muscle cells from a contractile phenotype (VSMC-C) into a synthetic phenotype (VSMC-S). In the tunica media, VSMC-S produced matrix and extracellular vesicles, forming mineralizable granules associated with arterial mineralization. VSMC-S were also present in the tunica intima, but matrix and extracellular vesicles and mineralization were not observed. The absence of matrix and extracellular vesicles in the intimal hyperplasia, even in the presence of noncollagenous bone proteins, tissue-nonspecific alkaline phosphatase, and vitamin D receptors, reinforces the hypothesis that the presence of matrix and extracellular vesicles are crucial for the development of vascular mineralization in enzootic calcinosis. It is proposed that the two different VSMC-S phenotypes in calcinosis are due to the expression of at least two genetically different types of these cells induced by the action of 1,25(OH) 2 D 3 .

Interstitial lung disease (ILD) is a common manifestation in connective tissue diseases (CTD), such as rheumatoid arthritis (RA), systemic sclerosis (SSc), and inflammatory myositis (IM). ILD is associated with significant morbidity and mortality in nearly all CTD highlighting the critical need for effective treatment strategies in this patient population. In this review, we will summarize the approach to treatment when there is concern for CTD-ILD and highlight recent advancements in therapeutics within various forms of CTD-ILD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

An outbreak of Ricinus communis poisoning in goats with neurological and digestive changes was related to the ingestion of different vegetative parts of the plant. Two poisoned animals died within 5 h of the plant intake showing necrotic gastroenteritis and hepatocytes degeneration and necrosis. Toxicological analysis by HPLC-DAD assay demonstrated 21.1-25.1 μg/g of ricinine in samples of ruminal fluids and 10.1-10.9 μg/g in the liver of poisoned goats., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans.

The early detection and diagnosis of deaths in free-ranging non-human primates (NHPs) are key points for the surveillance of Yellow Fever (YF) in Brazil. The histopathological identification of infectious diseases remains very useful and reliable in the screening and detection of emerging zoonotic diseases such as YF. We surveyed data records and liver slides stained with hematoxylin and eosin from the Epizootics Surveillance Network to control YF, Ministry of Health of Brazil, to evaluate histopathological hallmarks for the diagnosis of the YF virus infection. We selected natural fatal cases in NHPs from the genera Alouatta spp., Callithrix spp., and Sapajus spp. with a positive immunohistochemical assay for YF in liver samples. Our findings showed the full-spectrum YF-associated hepatic lesions in all NHPs, but some histopathological findings differed in the distribution and intensity between the three genera. In our study, South American NHPs showed significant differences in the YF-associated hepatic histopathological features compared to fatal cases reported in humans., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ocimum campechianum Mill. (Peruvian basil) is an essential oil-bearing plant of the Lamiaceae family. Volatile oil produced through steam distillation of Peruvian basil was examined to establish the aromatic and stable isotope profiles of samples ( n = 9) from three different cultivated plots in Peru. The resulting essential oils were analyzed by GC/FID, GC/MS, and GC/IRMS. In accordance with findings from other researchers, multiple chemotypes, defined by the most abundant aromatic compounds, exist within these populations. Overall, 55% of samples are the eugenol chemotype (values ranging 15.4-30.2%), 33% are the methyl eugenol chemotype (values ranging 68.1-68.7%), and a single sample is a mixture of both chemotypes, containing high levels of both eugenol (38.1%) and methyl eugenol (8.6%). Stable isotope ratios, δ 2 H and δ 13 C, performed on prominent compounds provide supporting data for distinguishing chemotypes. Complete aromatic profiles, stable isotope ratios, and essential oil yield are established for each sample. This study confirms the existence of multiple chemotypes and, for the first time, to the author's best knowledge, establishes stable isotope ratios for O. campechianum essential oil, which proves a useful tool in further investigating plant metabolism and determining essential oil authenticity.

Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals.

In collaboration with the American College of Veterinary Pathologists.

Leptospirosis is a zoonotic neglected disease of worldwide public health concern. Leptospira species can infect a wide range of wild and domestic mammals and lead to a spectrum of disease, including severe and fatal forms. Herein, we report for the first time a fatal Leptospira interrogans infection in a free-ranging nonhuman primate (NHP), a black-tufted marmoset. Icterus, pulmonary haemorrhage, interstitial nephritis, and hepatocellular dissociation were the main findings raising the suspicion of leptospirosis. Diagnostic confirmation was based on specific immunohistochemical and PCR assays for Leptospira species. Immunolocalization of leptospiral antigens and identification of pathogenic species (L. interrogans species) were important for better understanding the pathogenesis of the disease. One Health-related implications of free-ranging NHPs in anthropized areas and transmission dynamics of human and animal leptospirosis are discussed., (© 2021 Wiley-VCH GmbH. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: The COVID-19 pandemic has had a significant impact on the health system worldwide. The organ and tissue donation and transplantation (OTDT) system is no exception and has had to face ethical challenges related to the pandemic, such as risks of infection and resource allocation. In this setting, many Canadian transplant programs halted their activities during the first wave of the pandemic., Method: To inform future ethical guidelines related to the COVID-19 pandemic or other public health emergencies of international concern, we conducted a literature review to summarize the ethical issues., Results: This literature review identified three categories of ethical challenges. The first one describes the general ethical issues and challenges reported by OTDT organizations and transplantation programs, such as risks of COVID-19 transmission and infection to transplant recipients and healthcare professionals during the transplant process, risk of patient waitlist mortality or further resource strain where transplant procedures have been delayed or halted, and resource allocation. The second category describes ethical challenges related to informed consent in the context of uncertainty and virtual consent. Finally, the third category describes ethical issues related to organ allocation, such as social considerations in selecting transplant candidates., Conclusion: This literature review highlights the salient ethical issues related to OTDT during the current COVID-19 pandemic. As medical and scientific knowledge about COVID-19 increases, the uncertainties related to this disease will decrease and the associated ethical issues will continue to evolve., (© 2021. The Author(s).)

The coronavirus 2019 (COVID-19) pandemic has disrupted health systems worldwide, including solid organ donation and transplantation programs. Guidance on how best to screen patients who are potential organ donors to minimize the risks of COVID-19 as well as how best to manage immunosuppression and reduce the risk of COVID-19 and manage infection in solid organ transplant recipients (SOTr) is needed., Methods: Iterative literature searches were conducted, the last being January 2021, by a team of 3 information specialists. Stakeholders representing key groups undertook the systematic reviews and generation of recommendations using a rapid response approach that respected the Appraisal of Guidelines for Research and Evaluation II and Grading of Recommendations, Assessment, Development and Evaluations frameworks., Results: The systematic reviews addressed multiple questions of interest. In this guidance document, we make 4 strong recommendations, 7 weak recommendations, 3 good practice statements, and 3 statements of "no recommendation.", Conclusions: SOTr and patients on the waitlist are populations of interest in the COVID-19 pandemic. Currently, there is a paucity of high-quality evidence to guide decisions around deceased donation assessments and the management of SOTr and waitlist patients. Inclusion of these populations in clinical trials of therapeutic interventions, including vaccine candidates, is essential to guide best practices., Competing Interests: The authors have no relevant conflicts of interest to disclose., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

In this paper, we describe poisoning outbreaks of Xanthium strumarium in cattle on the borders of the Araguari River, Southeastern Brazil. In this region, several hydroelectric plants promote transient flooding, which creates a favorable environment for the invasion of X. strumarium in extensive areas, often as the predominant species in those areas. The outbreaks occurred between July and September (dry season). Bovines of all ages were affected, including suckling animals. Mortality varied from 2% to 5.5%. The animals exhibited ataxia, weakness, loss of balance, recumbency, and the majority were found dead. Laboratory results showed a marked increase in the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase. Histological and ultrastructural changes in the liver consisted of centrilobular necrosis and hemorrhage. On toxicological evaluation, the dicotyledons contained 0.30 μg/mg of atractyloside and 0.37 μg/mg of carboxyatractyloside. Considerable economic loss has occurred in this region due to the lack of knowledge regarding X. strumarium as a toxic plant and its adaptation to the environmental and climatic conditions of the region, which have made the condition endemic., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The present report describes the clinical and pathological changes induced by the consumption of oats contaminated with Crotalaria spectabilis seeds by horses. Eighty horses were exposed to oats containing 10 g/kg of C. spectabilis seeds with 0.46% pyrrolizidine alkaloids, and 21 horses died within a 6-month period. Clinical signs included jaundice, apathy, a hypotonic tongue, ataxia, hyporexia, weight loss, aimless wandering, violent behavior, and proprioceptive deficits. Pathological findings were predominant in the liver and included periportal bridging fibrosis, megalocytosis, centrilobular necrosis, and bile stasis. Other findings were Alzheimer's type II astrocytes in the cortex, midbrain, basal nuclei, brainstem and pons; multifocal edema and hemorrhage in the lungs; and degeneration and necrosis of the tubular epithelium of kidneys. Horses are highly sensitive to pyrrolizidine alkaloid-containing plants, and the observed clinical and pathological findings are typical of this poisoning. The seeds were planted, and botanical identification of the adult plants confirmed the diagnosis of C. spectabilis poisoning., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: The use of online platforms for pediatric healthcare research is timely, given the current pandemic. These platforms facilitate trial efficiency integration including electronic consent, randomization, collection of patient/family survey data, delivery of an intervention, and basic data analysis., Methods: We created an online digital platform for a multicenter study that delivered an intervention for sleep disorders to parents of children with autism spectrum disorder (ASD). An advisory parent group provided input. Participants were randomized to receive either a sleep education pamphlet only or the sleep education pamphlet plus three quick-tips sheets and two videos that reinforced the material in the pamphlet (multimedia materials). Three measures - Family Inventory of Sleep Habits (FISH), Children's Sleep Habits Questionnaire modified for ASD (CSHQ-ASD), and Parenting Sense of Competence (PSOC) - were completed before and after 12 weeks of sleep education., Results: Enrollment exceeded recruitment goals. Trial efficiency was improved, especially in data entry and automatic notification of participants related to survey completion. Most families commented favorably on the study. While study measures did not improve with treatment in either group (pamphlet or multimedia materials), parents reporting an improvement of ≥3 points in the FISH score showed a significantly improved change in the total CSHQ ( P = 0.038)., Conclusion: Our study demonstrates the feasibility of using online research delivery platforms to support studies in ASD, and more broadly, pediatric clinical and translational research. Online platforms may increase participant inclusion in enrollment and increase convenience and safety for participants and study personnel., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2021.)

The mammalian sex chromosome system (XX female/XY male) is ancient and highly conserved. The sex chromosome karyotype of the creeping vole ( Microtus oregoni ) represents a long-standing anomaly, with an X chromosome that is unpaired in females (X0) and exclusively maternally transmitted. We produced a highly contiguous male genome assembly, together with short-read genomes and transcriptomes for both sexes. We show that M. oregoni has lost an independently segregating Y chromosome and that the male-specific sex chromosome is a second X chromosome that is largely homologous to the maternally transmitted X. Both maternally inherited and male-specific sex chromosomes carry fragments of the ancestral Y chromosome. Consequences of this recently transformed sex chromosome system include Y-like degeneration and gene amplification on the male-specific X, expression of ancestral Y-linked genes in females, and X inactivation of the male-specific chromosome in male somatic cells. The genome of M. oregoni elucidates the processes that shape the gene content and dosage of mammalian sex chromosomes and exemplifies a rare case of plasticity in an ancient sex chromosome system., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shares common clinicopathologic features with other severe pulmonary illnesses. Hantavirus pulmonary syndrome was diagnosed in 2 patients in Arizona, USA, suspected of dying from infection with SARS-CoV-2. Differential diagnoses and possible co-infections should be considered for cases of respiratory distress during the SARS-CoV-2 pandemic.

Lavandula angustifolia Mill. (lavender) is an essential-oil-bearing plant in the Lamiaceae family. Volatile oil produced through the steam distillation of lavender was examined to establish the essential oil yield and aromatic profile from each portion of the plant-namely, the corolla, calyx, leaf, and whole flowering top. The resulting essential oils were analyzed by GC-FID and GC-MS. The different plant parts generally shared similar compounds but in varying relative percentages. Aromatic profiles of the whole flowering top and calyx were similar, with prominent compounds being linalool acetate (34.3%, 32.0%), linalool (26.5%, 32.9%), lavandulyl acetate (5.6%, 4.9%), terpinen-4-ol (5.3%, 7.0%), and ( Z )-β-ocimene (4.5%, 5.4%), respectively. Aromatic profiles for the corolla and leaf were unique. Prominent aromatic compounds of the corolla included linalool acetate (18.4%), linalool (10.8%), epi-α-cadinol (10.0%), borneol (7.3%), and lavandulyl acetate (6.3%). Prominent aromatic compounds of the leaf included epi-α-cadinol (19.8%), γ-cadinene (11.0%), borneol (6.0%), caryophyllene oxide (4.9%), and bornyl acetate (4.8%). Complete profiles and essential oil yields of corolla, calyx, leaf, and whole flowering top were established. This study establishes the influence the corolla, calyx, and leaf exert on the aromatic profile of the whole flowering top and provides insight into authentication of lavender essential oil.

Pancreatic eurytrematosis (PE) is an under diagnosed and neglected parasitosis in goats and sheep in the Americas. Clinical and pathological features of PE are not well defined in small ruminants worldwide. Natural cases of PE in small ruminants were detected in the Federal District, Brazil. A survey of necropsy records, including epidemiological and clinicopathological data, in goats and sheep was conducted. Most cases of PE occurred during the rainy season in adult females, with an incidence of 12.9% in goats and 0.8% in sheep. Clinical signs varied from asymptomatic infections to anorexia, lethargy, weakness, marked weight loss and death in some goats. Overall, most cases of PE in goats and sheep were incidental necropsy findings with minor pancreatic lesions. Three goats, however, showed severe chronic pancreatitis, dilation of major pancreatic ducts with numerous trematodes present and marked abdominal fat necrosis. Morphological and molecular characterization of flukes detected Eurytrema coelomaticum. Our findings shed light on the prevalence of E. coelomaticum infections in small ruminants in the region and highlight the possibility of severe and lethal cases in goats. PE must be further investigated in small ruminant populations in relevant livestock production regions of the Americas.

Squamous cell carcinomas (SCC) are one of the most common tumors of the tegument that can have a misdiagnosis of chronic skin wounds. An adult captive crowned solitary eagle presented an indolent wound-like ulcer on the footpad and a fatal outcome. An infiltrating tumoral mass in the foot and multiple tumoral metastatic nodules in visceral organs were detected. The neoplasm was composed of atypical squamous cells with strong positivity for cytokeratin, "keratin pearl" structures, and marked invasion of tissues confirming a diagnosis of metastatic SCC. This might be the first report of an SSC with metastasis on the footpad in a captive Chaco eagle, which is one of the endangered species of birds of prey.

Purpose of Review: This review will summarize recent data defining the relationship between rheumatoid arthritis (RA) and the microbiome at mucosal sites throughout the body. It will highlight what is known, what is speculated, and current knowledge gaps regarding the microbiome in RA., Recent Findings: An extensive relationship between the microbiome and immune cell function can influence RA-related inflammation and T cell and B cell biology. Studies are beginning to characterize microbial changes in individuals who are at risk for RA, which is a critical element needed to understand the influence of the microbiome on RA pathogenesis. Expanding our understanding of the microbiome in RA beyond the bacteria at the gut and oral mucosae into the lung and urogenital surfaces, including viral and fungal components, and establishing the relationship across mucosal sites will be critical in future work. Importantly, approaches to manipulate the microbiome could lead to novel therapeutic and preventive strategies.

Uraemic encephalopathy (UE) is rarely associated with acute kidney injury or chronic kidney disease in domestic animals, and we now report the first case in a cat. The animal presented with hypothermia, apathy, lethargy, depression, severe dehydration, uraemic breath, elevated serum urea nitrogen and creatine concentrations, and eventual seizures and coma prior to death. Gross necropsy findings included severe bilateral renal scarring, ulcerative stomatitis and glossitis, and uraemic gastropathy. Microscopic lesions of diffuse interstitial fibrosis, multifocal mineralization and lymphoplasmacytic interstitial nephritis were seen in the kidneys. There was symmetrical, bilateral spongy vacuolation of the white matter of the basal nuclei and cerebellum and Alzheimer type II astrocytes in the cerebral cortex and hippocampus. Glial fibrillary acid protein immunolabelling was absent or faint in astrocytes of the cerebral grey matter. UE should be included in the differential diagnosis in animals with chronic kidney disease and neurological signs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Four formulations of an investigational tetravalent dengue purified inactivated vaccine, administered as two doses one month (M) apart, were previously shown to be immunogenic and well-tolerated up to M13 of the phase I study NCT01702857. Here, we report results of the follow-up from M14 to year (Y) 3. One hundred healthy Puerto Rican adults, predominantly dengue virus (DENV)-primed, were randomized 1:1:1:1:1 to receive placebo or vaccine formulations: 1 μg/serotype/dose adjuvanted with aluminum, AS01 E or AS03 B , or aluminum-adjuvanted 4 μg/serotype/dose. No serious adverse events occurred. Two medically-attended potential immune-mediated disease cases, vaccination unrelated, were reported (groups 1 µg+Alum and 1 µg+AS03 B ). Of 14 instances of suspected dengue, none were laboratory confirmed. Geometric mean neutralizing antibody titers against DENV 1-4 waned from M14, but remained above pre-vaccination levels for DENV 1-3, with the highest values for group 1 µg+AS03 B : 1220.1, 920.5, 819.4, and 940.5 (Y2), and 1329.3, 1169.2, 1219.8, and 718.9 (Y3). All formulations appeared to be safe and immunogenic during the 3-year follow-up.

Shrinking natural habitats exposes some non-human primates to the risk of accidents associated with electrical transmission lines. We examined dead marmosets (Callithrix penicillata) collected in the region from January 2015 to April 2018 to determine the animals' cause of death and for electrocuted animals we examined the locations the animals had died as well as the configuration of the power lines at these sites. We also recorded the sex of the animal, the body region affected, and characteristics of the injuries. We diagnosed electrocutions in 11% (n = 34) of the marmosets studied. Most of the affected animals were male (n = 22) with single or double sites of injury on the limbs. Animals were injured in urban (n = 26) and peri-urban (n = 8) areas on lower-voltage alternate current lines, and we detected no seasonality or hotspots of electrocution. Our findings suggest that movement along transmission lines composed of bundled conductors is a major factor in electrocutions of marmosets in the Federal District and surrounding areas. The planning of electrical power grid infrastructure should consider arboreal primates to prevent electrocutions.

The primary manifestation of rheumatoid arthritis (RA) is articular disease; however, extra-articular disease can also occur. In particular, pulmonary disease is a leading cause of morbidity and mortality in individuals with RA. Herein, we will review the types, prevalence, risk factors, and potential pathophysiology of lung disease in individuals with established RA. We will also discuss the emerging understanding of potential role of the lung in the generation of RA-related autoantibodies during a period of disease development termed "pre-RA." Finally, we will discuss a research agenda outlining the next steps to improve our understanding and management of lung inflammation and lung disease throughout the natural history of RA., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)