Search Results (43)

A previously buried paleosol was found on the continental shelf during a study of sea floor scour, nucleated by large artificial reef structures such as vessel hulks, barges, train cars, military vehicles, etc., called “scour nuclei”. It is a relic paleo-land surface of sapling-sized tree stumps, root systems, and fossil animal bone exhumed by scour processes active adjacent to the artificial reef structure. Over the span of five research cruises to the site in 2022–2024, soil samples were taken using hand excavation, PONAR grab samplers, split spoon, hollow tube auger, and a modified Shelby-style push box. High-definition (HD) video was taken using a Remotely Operated Vehicle (ROV) and diver-held cameras. Radiocarbon dating of wood samples returned ages of 42,015–43,417 calibrated years before present (cal yrBP). Pollen studies, together with the recovered macrobotanical remains, support our interpretation of the site as a freshwater forested wetland whose keystone tree species was Taxodium distichum—bald cypress. The paleosol was identified as an Aquult, a sub-order of Ultisols where water tables are at or near the surface year-round. A deep (0.25 m+) argillic horizon comprised the bulk of the preserved soil. Comparable Ultisols found in Georgia wetlands include Typic Paleaquult (Grady and Bayboro series) soils. Full article

Background/Objectives: Parkinson’s disease (PD) is a complex neurodegenerative disorder that presents significant challenges for care home residents and staff. This scoping review aimed to synthesize evidence on PD education and training available to care home staff, examine existing programs and their effectiveness, and identify gaps in current educational approaches. Methods: A scoping review (ScR) was conducted and guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for ScR (PRISMA-ScR) checklist. A comprehensive search of six electronic databases was conducted in September 2024. Studies focusing on PD education and training for care home staff were included. Data extraction and quality appraisal were performed, followed by thematic analysis to identify key patterns and themes. Results: Seven studies met the inclusion criteria. The thematic analysis revealed four main themes: improvements in PD knowledge and confidence, improvements in care practices and outcomes, the need for increased specialist education, and the incorporation of communication training. Educational interventions led to significant improvements in staff knowledge, confidence, and care practices. However, these studies also highlighted a critical need for more specialized PD training among care home staff. Conclusions: This review provides evidence of promise regarding the potential impact of PD-specific education on care home staff knowledge and practices. Future research should focus on developing and evaluating comprehensive, tailored educational programs to enhance the quality of care for people with PD in care home settings. Full article

Technological developments have allowed helicopter airborne laser scanning (HALS) to produce high-density point clouds below the forest canopy. We present a tree stem classification method that combines linear shape detection and model-based clustering, using four discrete methods to estimate stem diameter. Stem horizontal size was estimated every 25 cm below the living crown, and a cubic spline was used to estimate where there were gaps. Individual stem diameter at breast height (DBH) was estimated for 77% of field-measured trees. The root mean square error (RMSE) of DBH estimates was 7–12 cm using stem circle fitting. Adapting the approach to use an existing stem taper model reduced the RMSE of estimates (<1 cm). In contrast, estimates that were produced from a previously existing DBH estimation method (PREV) could be achieved for 100% of stems (DBH RMSE 6 cm), but only after location-specific error was corrected. The stem classification method required comparatively little development of statistical models to provide estimates, which ultimately had a similar level of accuracy (RMSE < 1 cm) to PREV. HALS datasets can measure broad-scale forest plantations and reduce field efforts and should be considered an important tool for aiding in inventory creation and decision-making within forest management. Full article

Kojic acid is a secondary metabolite with strong chelating and antioxidant properties produced by Aspergillus flavus and A. oryzae. Although antioxidants and chelators are important virulence factors for plant pathogens, the ecological role of kojic acid remains unclear. We previously observed a greater gene expression of antioxidants, especially kojic acid, by non-aflatoxigenic A. flavus when co-cultured with aflatoxigenic A. flavus. Aflatoxin production was also reduced. In this study, we investigated kojic acid production in 22 A. flavus isolates from Louisiana and compared them to four common A. flavus strains in liquid medium and on corn kernels. Corn kernel infection was assessed by quantifying the maize beta tubulin DNA content of the kernels using drop digital PCR (ddPCR). Maize beta tubulin DNA content decreased with increased corn kernel infection. Greater kojic acid production by A. flavus isolates coincided with greater levels of corn kernel infection. All isolates produced 60 and 700 times more kojic acid than aflatoxin and cyclopiazonic acid (a known virulence factor), respectively, which varied among sclerotial size categories. A. flavus strains with small sclerotia, which were rarely isolated from corn, produced the least kojic acid and infected corn kernels the least, while medium and large sclerotia strains—mainly isolated from corn—produced the most kojic acid and were more infectious. Non-aflatoxigenic isolates from Louisiana produced the most kojic acid. These results suggest that kojic acid is a potential virulence factor and may increase the pathogenic success of medium and large sclerotia-producing A. flavus, which could ultimately lead to more effective A. flavus biocontrol strains. Further studies are required to determine the effects that kojic acid has on the redox environment during corn infection and how the altered redox environment decreases aflatoxin production. Full article

The binding of small molecules to sarcomeric myosin can elicit powerful effects on the chemomechanical cycle, making them effective therapeutics in the clinic and research tools at the benchtop. However, these myotropes can have complex effects that act on different phases of the crossbridge cycle and which depend on structural, dynamic, and environmental variables. While small molecule binding sites have been identified crystallographically and their effects on contraction studied extensively, small molecule-induced dynamic changes that link structure–function are less studied. Here, we use molecular dynamics simulations to explore how omecamtiv mecarbil (OM), a cardiac myosin-specific myotrope, alters the coordinated dynamics of the lever arm and the motor domain in the pre-powerstroke state. We show that the lever arm adopts a range of orientations and find that different lever arm orientations are accompanied by changes in the hydrogen bonding patterns near the converter. We find that the binding of OM to myosin reduces the conformational heterogeneity of the lever arm orientation and also adjusts the average lever arm orientation. Finally, we map out the distinct conformations and ligand–protein interactions adopted by OM. These results uncover some structural factors that govern the motor domain–tail orientations and the mechanisms by which OM primes the pre-powerstroke myosin heads. Full article

Aspergillus flavus, a fungus known for producing aflatoxins, poses significant threats to agriculture and global health. Flavonoids, plant-derived compounds, inhibit A. flavus proliferation and mitigate aflatoxin production, although the precise molecular and physical mechanisms underlying these effects remain poorly understood. In this study, we investigated three flavonoids—apigenin, luteolin, and quercetin—applied to A. flavus NRRL 3357. We determined the following: (1) glycosylated luteolin led to a 10% reduction in maximum fungal growth capacity; (2) quercetin affected cell wall integrity by triggering extreme mycelial collapse, while apigenin and luteolin caused peeling of the outer layer of cell wall; (3) luteolin exhibited the highest antioxidant capacity in the environment compared to apigenin and quercetin; (4) osmotic stress assays did not reveal morphological defects; (5) flavonoids promoted cell adherence, a precursor for biofilm formation; and (6) RNA sequencing analysis revealed that flavonoids impact expression of putative cell wall and plasma membrane biosynthesis genes. Our findings suggest that the differential effects of quercetin, luteolin, and apigenin on membrane integrity and biofilm formation may be driven by their interactions with fungal cell walls. These insights may inform the development of novel antifungal additives or plant breeding strategies focusing on plant-derived compounds in crop protection. Full article

Finding prehistoric sites, on the sea floor off the United States, has proven to be a difficult task. Over four decades of innovative attempts have produced few discoveries. This discussion outlines the difficulties in finding submerged prehistory on the sea floor, examines current methodology(ies), and presents a new methodology that demonstrates promise based on research conducted over the past decade. The purpose of this discussion is to outline the problems facing archaeologists searching the sea floor for archaeological sites. It is less of a critique of past efforts and methodologies used in those attempts. Without those efforts, a reason for developing a different methodological approach would be unnecessary. Any “one size fits all” methodology is limiting, and the scant number of marine archaeological sites located off the shores of the United States can attest to the need for practitioners to continue refining their methods. This is especially the case on the continental shelf of the eastern United States, where sediment cover is often meters, or several meters, thick. This opportunistic methodology developed on the continental shelf of the Georgia Bight, western Atlantic Ocean, has located intact paleo-landforms with in situ, palaeoecological remains thereby offering promise for future archaeological discoveries. Full article

Background: Incidence of disability secondary to Parkinson’s disease is increasing faster globally than any other neurological condition. The diverse appearance of symptomatology associated with Parkinson’s, and the degenerative nature and subsequent functional decline, often increase dependence on caregivers for assistance with daily living, most commonly within a care home setting. Yet, primary literature and evidence synthesis surrounding these unique and complex care needs, challenges and the lived experiences of this population living in long-term nursing or residential facilities remains sparce. The aim of this review is to synthesize qualitative literature about the lived experience of people with Parkinson’s disease living in care home settings. Methods: A systematic search of the literature was conducted in October 2023 across six different databases (CINAHL, Medline, EMBASE, PsycINFO, Scopus and Cochrane Library). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to guide this review. Results: Five articles met the inclusion criteria. Four themes were identified following evidence synthesis: (1) Unique pharmacological challenges. (2) Transitioning and adapting to care home life and routines. (3) Dignified care within care homes. (4) Multidisciplinary care vacuum in care homes. Conclusion: This review revealed the significant and unique challenges for people with Parkinson’s disease when transitioning into care homes. These are exacerbated by wider social care challenges such as staffing levels, skill mixes and attitudes as well as a lack of disease-specific knowledge surrounding symptomatology and pharmacology. The lack of multi-disciplinary working and risk-adverse practice inhibited person-centred care and autonomy and reduced the quality of life of people living with Parkinson’s disease in care homes. Recommendations for practice highlight training gaps, the need for consistent and improved interdisciplinary working and better person-centred assessment and care delivery. Full article

Cutaneous wound healing consists of four stages: hemostasis, inflammation, proliferation/repair, and remodeling. While healthy wounds normally heal in four to six weeks, a variety of underlying medical conditions can impair the progression through the stages of wound healing, resulting in the development of chronic, non-healing wounds. Great progress has been made in developing wound dressings and improving surgical techniques, yet challenges remain in finding effective therapeutics that directly promote healing. This review examines the current understanding of the pro-healing effects of targeted pharmaceuticals, re-purposed drugs, natural products, and cell-based therapies on the various cell types present in normal and chronic wounds. Overall, despite several promising studies, there remains only one therapeutic approved by the United States Food and Drug Administration (FDA), Becaplermin, shown to significantly improve wound closure in the clinic. This highlights the need for new approaches aimed at understanding and targeting the underlying mechanisms impeding wound closure and moving the field from the management of chronic wounds towards resolving wounds. Full article

Shakespeare’s Henry VI trilogy is jam-packed with spectacle: heads are severed and made to kiss, women dress as men and lead armies, ghosts predict the future, and a plethora of miracles take place all over the various locales we visit across fifteen acts. In fact, if “faith is… the evidence of things not seen,” as asserted by the author of Hebrews, then the Henry VI plays are entirely devoid of faith, by the merit of bringing miraculous events from the realm of faith into the realm of observational knowledge. Of note, then, is the fact that the trilogy depicts Henry as a weak king whose main virtue is his commitment to his faith. Compared to other kings in Shakespearean history plays, Henry is almost-constantly referencing the spiritual world, and the world he lives in is so full of miraculous happenings that miracles themselves run the risk of becoming banal. Perhaps surprisingly, given the trilogy’s thematic investment in miracles and spirituality, the English are defined in the plays as destroying or debunking miraculous spectacles. From Gloucester outsmarting Simpcox in his feigned healing to the putting-down of two witches (Joan in 1 Henry VI and Margery Jourdain in 2 Henry VI), it seems that, despite Henry’s incredible devotion, his courtiers raise skepticism to the level of modus operandi. In this essay, I hope to examine the way that the second Henriad depicts a version of England that places logic and skepticism in the seat of faith, while its ruler’s faith is often both uninterrogated and misplaced. Shakespeare stages a teleology of spectacle that highlights English faithlessness as a source of internecine struggle and insurrection, while also cautioning against naivete in the face of canny nemeses. Full article

The brain is traditionally viewed as an immunologically privileged site; however, there are known to be multiple resident immune cells that influence the CNS environment and are reactive to extra-CNS signaling. Microglia are an important component of this system, which influences early neurodevelopment in addition to modulating inflammation and regenerative responses to injury and infection. Microglia are influenced by gut microbiome-derived metabolites, both as part of their normal function and potentially in pathological patterns that may induce neurodevelopmental disabilities or behavioral changes. This review aims to summarize the mounting evidence indicating that, not only is the Gut–Brain axis mediated by metabolites and microglia throughout an organism’s lifetime, but it is also influenced prenatally by maternal microbiome and diet, which holds implications for both early neuropathology and neurodevelopment. Full article

Objective: Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses. Methods: DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriber-related beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers’ dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines. Results: In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years’ experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk. Conclusions: Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing. Full article

Chorioamnionitis remains a major cause of preterm birth and maternal and neonatal morbidity. We reviewed the current evidence for the diagnostic tests of chorioamnionitis and how this relates to clinical practice today. A comprehensive literature search and review was conducted on chorioamnionitis and intra-uterine inflammation. Data from randomized control trials and systematic reviews were prioritized. This review highlights that sterile inflammation plays an important role in chorioamnionitis and that the current tests for chorioamnionitis including clinical criteria, maternal plasma and vaginal biomarkers lack diagnostic accuracy. Concerningly, these tests often rely on detecting an inflammatory response after damage has occurred to the fetus. Care should be taken when interpreting current investigations for the diagnosis of chorioamnionitis and how they guide obstetric/neonatal management. There is an urgent need for further validation of current diagnostic tests and the development of novel, accurate, minimally invasive tests that detect subclinical intra-uterine inflammation. Full article

A field biologist was bitten by a female Nikolsky’s viper (Vipera berus nikolskii) in Kharkiv Oblast, Ukraine. Two months later, the patient began to experience cold-induced vasospasm of the affected digit diagnosed as acquired Raynaud phenomenon. The patient had more than 30 occurrences during the single winter following the bite, but the signs and symptoms of Raynaud phenomenon disappeared with the end of winter. This report describes the case and puts it into context with the literature on the topic of toxin-induced peripheral vasospastic disorders and their potential importance in snakebite envenoming. Full article

Antivenom is currently the standard-of-care treatment for snakebite envenoming, but its efficacy is limited by treatment delays, availability, and in many cases, species specificity. Many of the rapidly lethal effects of envenoming are caused by venom-derived toxins, such as phospholipase A2 (sPLA2); therefore, small molecule direct toxin inhibitors targeting these toxins may have utility as initial and adjunct therapies after envenoming. Varespladib (intravenous, IV) and varespladib-methyl (oral) have been shown to potently inhibit sPLA2s from snake venoms in murine and porcine models, thus supporting their further study as potential treatments for snakebite envenoming. In this pilot study, we tested the ability of these compounds to reverse neurotoxic effects of venom from the Australian and Papuan taipan (Oxyuranus scutellatus) subspecies in juvenile pigs (Sus domesticus). The mean survival time for control animals receiving Australian taipan venom (0.03 mg/kg, n = 3) was 331 min ± 15 min; for those receiving Papuan taipan venom (0.15 mg/kg, n = 3) it was 178 ± 31 min. Thirteen pigs received Australian taipan venom and treatment with either IV or oral varespladib (or with IV to oral transition) and all 13 survived the duration of the study (≥96 h). Eight pigs received Papuan taipan venom followed by treatment: Briefly: Two animals received antivenom immediately and survived to the end of the study. Two animals received antivenom treatment delayed 45 min from envenoming and died within 4 h. Two animals received similarly delayed antivenom treatment and were rescued by varespladib. Two animals were treated with varespladib alone after a 45-min delay. Treatment with varespladib only was effective but required repeat dosing over the course of the study. Findings highlight both the importance of early treatment and, as well, a half-life for the investigational inhibitors now in Phase II clinical trials for snakebite. Varespladib rapidly reversed weakness even when administered many hours post-envenoming and, overall, our results suggest that varespladib and varespladib-methyl could be efficacious tools in the treatment of sPLA2-induced weakness from Oxyuranus envenoming. Further clinical study as initial therapy and as potential method of rescue from some types of antivenom-resistant envenomings are supported by these data. Full article