Search Results (447)

The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous leaf extracts from two plants commonly found in North America, Osage orange (M. pomifera) and spearmint (M. spicata). Both extracts exhibited no significant cytotoxic or morphologic impact on HEp-2 human cancer cells up to 25 mg/mL. However, both extracts demonstrated strong dose-dependent antibacterial activity, significantly inhibiting replication of E. coli and S. aureus at concentrations ≥ 1 mg/mL. Antiviral assays revealed that both extracts inhibited hRSV infectivity, with spearmint extract showing higher potency (EC₅₀ = 1.01 mg/mL) compared to Osage orange (EC₅₀ = 3.85 mg/mL). Gas chromatography–mass spectrometry (GC-MS) identified three major extract constituents: 3-hydroxybenzyl alcohol, 4-hydroxybenzyl alcohol (Osage orange), and R-(-)-carvone (spearmint). Among these, only carvone significantly inhibited hRSV in vitro, suggesting its key role in spearmint’s antiviral activity. These findings highlight the therapeutic potential of Osage orange and spearmint leaf extracts, particularly as sources of water-soluble compounds with antimicrobial properties, and support further investigation into their mechanisms of action and broader clinical relevance. Full article

The demand for land monitoring information continues to increase, but the range and diversity of the available products to date have made their integrated use challenging and, at times, counterproductive. There has therefore been a growing need to enhance and harmonise the practice of land monitoring on a pan-European level with the formulation of a more consistent and standardised set of modelling criteria. The outcome has been a paradigm shift away from a “paper map”-based world where features are given a single, fixed label to one where features have a rich characterisation which is more informative, flexible and powerful. The approach allows the characteristics to be dynamic so that, over time, a feature may only change part of its description (i.e., a forest can be felled, but it may remain as forestry if replanted) or it can have multiple descriptors (i.e., a forest may be used for both timber production and recreation). The concept proposed by the authors has evolved since 2008 from first drafts to a comprehensive and powerful tool adopted by the European Union’s Copernicus programme. It provides for the semantic decomposition of existing nomenclatures, as well as supports a descriptive approach to the mapping of all landscape features in a flexible and object-oriented manner. In this way, the key move away from classification towards the characterisation of the Earth’s surface represents a novel and innovate approach to handling complex land surface information more suited to the age of distributed databases, cloud computing and object-oriented data modelling. In this paper, the motivation for and technical approach of the EAGLE concept with its matrix and UML model implementation are explained. This is followed by an update of the latest developments and the presentation of a number of experimental and operational use cases at national and European levels, and it then concludes with thoughts on the future outlook. Full article

In vitro tissue models offer a flexible complementary study system for use alongside in vivo human tissue samples. Achieving accurate in vitro models relies on combining appropriate scaffolds, growth factors and cell populations to recreate human tissue complexity. Balancing a consistent cell supply with the creation of healthy tissue models can be challenging; established cell lines are often cancerous, with altered cellular function compared to healthy populations, and primary cells require repeated isolation, with associated batch-to-batch variation. Pluripotent stem cell-derived populations offer a consistent supply, as well as the ability to model disease phenotypes through cell reprogramming using patient-derived cells. In this study, we have used an induced pluripotent stem cell-derived fibroblast population to develop a dermal equivalent model. These cells form a consistent tissue construct with a structure and composition similar to primary fibroblast controls, which are able to support an overlying epidermis. The resultant full-thickness skin model demonstrates the expression of various key skin-related markers, correctly localised within the organised epidermis, notably improving on previous models of a similar nature. Providing proof of concept using an established in vitro protocol, this study paves the way for future work developing consistent, customised, full-thickness human skin equivalents using iPSC-derived populations. Full article

Youth sport has been recognized as a unique learning context for positive youth development (PYD); yet, as society’s critical consciousness continues to progress, limitations of PYD have been acknowledged. Thus, youth sport scholars have begun to embrace critical perspectives to interrogate the systems and institutions of sport and society that influence the healthy development of all youth. This has included researchers and practitioners alike, adopting critical PYD (CPYD) as a means to empower young people to question and challenge their histo-contemporary experiences and support collective action towards social change. Our article explores the concept of CPYD and social justice life skills within ‘non-traditional’ sport spaces, including practice examples from the fields of youth disability sport and sport in youth justice. The first practice example provides an in-depth discussion of the theoretical principles of CPYD and their applicability within youth disability sport. The second practice example outlines the practical use of social justice life skills in sport programs within the youth justice system. Together, the practice examples from the field highlight both the theoretical and practical applications of CPYD and social justice life skills within real-world settings, and valuable implications are identified for research and practice moving forward. Full article

Zika virus (ZIKV) infection during pregnancy can cause a broad range of neurological birth defects, collectively named Congenital Zika Syndrome (CZS). We have previously shown that infection with the Puerto Rican isolate PRVABC59 (ZIKV-PR) results in abnormal oxygen transport in the placenta due to villous damage and uterine vasculitis in a nonhuman primate model. To investigate whether this type of damage occurs with endemically circulating strains in Thailand, we investigated a CZS case isolate, MU1-2017 (ZIKV-TH), in pregnant rhesus macaques. Pregnant animals (n = 3 per group) were infected subcutaneously with either ZIKV-PR or ZIKV-TH at ~50 days gestation (GD) and monitored for 40 days post-infection (GD90). Similar courses of viremia and immune activation were observed for both viruses when compared to uninfected controls. In addition, both viruses induced changes to the placental architecture, including spiral artery remodeling and the development of infarctions. Similar levels of viral RNA were detected at necropsy in maternal and fetal tissues. Overall, our results show that the ZIKV-TH strain MU1-2017 behaves similarly to the ZIKV-PR strain, and, importantly, provide evidence of in-utero infection with an additional contemporary strain of ZIKV. Full article

The implementation and practice of palliative medicine have numerous boundaries in low- and middle-income countries (LMICs), stemming from various cultural, legal, and religious concerns. Additionally, professional education in palliative care medicine in these countries is severely lacking, especially when compared with developed countries. Background/Objectives: To enhance and demystify palliative medicine practice to health care providers in LMICs. Methods: We developed a novel and comprehensive course in palliative care medicine and end-of-life (EOL) care, specifically within the context of management of patients with traumatic brain injury (TBI). We performed both immediate pre-course and post-course analysis of course participant comprehension and feedback, as well as a one-year post-course analysis and small group discussion. Results: The comprehension of the course material was strong, as participants scored an average of 13.9 points better on the post-test compared to the pre-test (49.6% vs. 35.7%, p < 0.001). Participants in the one-year follow-up session reported long-term applicability of the course material in their respective practice settings, with all participants reporting that they utilize the course material often. Small group discussion responses indicated a strong level of comprehension of the course material. Conclusions: Providing education in palliative medicine to health care professionals in LMICs is feasible, and likely to be both well-received and strongly influential to local medical practice. Local cultural and religious practices may be less of a barrier to the provision of palliative medicine than previously considered. Practicing palliative medicine, particularly at EOL, may strengthen patient–provider relationships, improve job satisfaction among health care providers, and improve the perception of medical care provided in LMIC medical settings. Full article

Sclerotinia sclerotiorum is a devastating fungal pathogen that can colonize numerous crops. Despite its economic importance, the regulation of its development and pathogenicity remains poorly understood. From a forward genetic screen in S. sclerotiorum, six UV mutants were identified with loss-of-function mutations in SsATG1, SsATG2, SsATG4, SsATG5, SsATG9, and SsATG26. Functional validation through gene knockouts revealed that each ATG is essential for sclerotia formation, although the morphology of appressoria was not significantly altered in the mutants. Different levels of virulence attenuation were observed among these mutants. Autophagy, monitored using GFP-ATG8, showed dynamic activities during sclerotia development. These findings suggest that macroautophagy and pexophagy contribute to sclerotia maturation and virulence processes. Future work will reveal how autophagy controls target organelle or protein turnover to regulate these processes. Full article

The monitoring and assessment of forest conditions has traditionally relied on continuous forest inventory (CFI) plots, where all plot trees are regularly measured at discrete locations, then plots are grouped as representative samples of forested areas via stand-based inventory expectations. Remote sensing data acquisitions, such as airborne laser scanning (ALS), are becoming more widely applied to operational forestry to derive similar stand-based inventories. Although ALS systems are widely applied to assess forest metrics associated with crowns and canopies, limited studies have compared ALS-derived digital inventories to CFI datasets. In this study, we conducted an analysis of over 1000 CFI plot locations on ~611,000 acres and compared it to a single-tree derived inventory. Inventory metrics from CFI data were forward modeled from 2016 to 2019 using the USDA Forest Service Forest Vegetation Simulator (FVS) to produce estimates of trees per acre (TPA), basal area (BA) per tree or per plot, basal area per acre (BAA), and volume per acre (VPA) and compared to the ALS-derived Digital Inventory^® (DI) of 2019. The CFI data provided greater on-plot tree counts, BA, and volume compared to the DI when limited to trees ≥5 inches DBH. On-plot differences were less significant for taller trees and increasingly diverged for shorter trees (<20 feet tall) known to be less detectable by ALS. The CFI volume was found to be 44% higher than the ALS-derived DI suggesting mean volume per acre as derived from plot sampling methods may not provide accurate results when expanded across the landscape given variable forest conditions not captured during sampling. These results provide support that when used together, CFI and DI datasets represent a powerful set of tools within the forest management toolkit. Full article

Objective: Current interventions for anxiety, depression, and insomnia are efficacious, yet effectiveness may be limited by side effects and/or high withdrawal rates. Other desirable treatment options are needed. Many veterans and civilians are turning to acupuncture as an emerging therapy. Our objective was to conduct a more definitive study comparing verum with sham acupuncture (minimal needling). Methods: A two-arm, single-blinded randomized controlled trial (RCT) hypothesizing that both verum and sham acupuncture are effective and the effects of verum are superior to those of sham acupuncture. We recruited subjects from a single outpatient-based site, the Tibor Rubin VA Medical Center, Long Beach, CA, USA. A total of 93 treatment-seeking combat Veterans with posttraumatic stress disorder (PTSD), aged 18–55, were allocated to groups by adaptive randomization, and 71 participants completed the intervention protocols. Verum and sham were both offered as 1 h sessions, twice a week, and participants were allowed 15-weeks to complete up to 24 sessions. This was a secondary analysis from a larger study about the efficacy of acupuncture for PTSD. Outcomes for the current study were pre- to post-intervention change in the Hamilton Anxiety Rating Scale, Beck Depression Inventory, and Pittsburgh Sleep Quality Index. Outcomes were assessed pre-, mid-, and post-treatment. General Linear Models comparing within- and between-group results were analyzed in both intention-to-treat (ITT) and treatment completer models. Results: In total, 85 males and 8 females, with a mean age of 39.2 (median = 37.0), were randomized. For anxiety, the verum acupuncture showed a large treatment effect (d = 1.3), whereas sham acupuncture showed a moderate effect (d = 0.9). There was no statistical difference between the verum and sham acupuncture groups. Similar effects were found for depression and insomnia symptoms. Withdrawal rates were low. Conclusions: Both verum and sham acupuncture were efficacious in the treatment of anxiety, depression, and insomnia in a population of veterans with PTSD. However, there was no clinical difference between the verum and sham acupuncture groups. These data build on extant literature and suggest that further research on the clinical implementation and durability of acupuncture for anxiety, depression, and insomnia is warranted. Full article

The Oddy test is an accelerated metal corrosion test used extensively by cultural institutions to determine the suitability of a material for use in museums. Alternatively, the use of gas chromatography-mass spectrometry (GC-MS) to directly identify volatile organic compounds (VOCs) from construction materials is growing in popularity because of its comprehensiveness and speed. Interpreting the reactivity of these potential pollutants, however, relies on ‘chemical intuition’ based on observed functional groups since the reactivity of only a handful of common VOCs has been studied intensively with regard to artworks. While short chain organic acids are known to be deleterious to some metals, polymers, and other culturally relevant materials, the common observation of lower volatility acids as well as their complementary aldehydes and esters in these offgassing experiments do not have clear indicators of their potential for artwork damage. In this work, the lead coupon, known to be a sensitive indicator of damaging organic acids, was exposed to known concentrations of a homologous series of organic acids, aldehydes, and esters from C2 to C18. Analysis of the coupon surface by infrared and Raman spectroscopies, and of the headspace within an Oddy jar by GC-MS, provides insights into the corrosion processes of these potential pollutants. Humidity was identified as a necessary component for corrosion to occur, and very volatile and semi-volatile compounds up to C9 created the corresponding lead carboxylate on the coupon surface in addition to lead carbonate. For higher order acids, and to a far lesser extent the esters and aldehydes, a high concentration of the VOC was necessary to induce small amounts of corrosion. In some instances, the gas phase chemistry of the reactor was particularly complex, suggesting mixtures of pollutants may prove more problematic to artist materials than single offgassed species. Full article

Background: Pancreatoduodenectomy with venous resection (PDVR) may be performed to achieve tumour clearance in patients with a pancreatic ductal adenocarcinoma (PDAC) with venous involvement. This study aimed to evaluate the impact of PDVR on PDAC outcomes. Methods: In total, 435 PDAC patients with either R0 status (n = 322) or R1 status within the superior mesenteric vein groove (n = 113) were extracted from the Recurrence After Whipple’s (RAW) study dataset. PDVR patients were matched in a 1:2 ratio with standard PD patients. Comparisons were then made between the two groups (surgical radicality and survival). Results: A total of 81 PDVRs were matched with 162 PDs. Neoadjuvant chemotherapy (5.7% vs. 13.6%, p = 0.032) and R1 resection rates (17.9% vs. 42%, p < 0.001) were higher in the PDVR group. Risk factors for R1 resection included venous resection (p < 0.001 for sleeve and p = 0.034 for segmental resection), pT3 (p = 0.007), and pN1 stage (p = 0.045). PDVR patients had lower median overall survival (OS, 21 vs. 30 months (m), p = 0.023) and disease-free survival (DFS, 17 m vs. 24 m, p = 0.043). Among PDVR patients, R status did not impact on OS (R0: 23 m, R1: 21 m, p = 0.928) or DFS (R0: 18 m, R1: 17 m, p = 0.558). Irrespective of R status, systemic recurrence was higher in the PDVR group (p = 0.034). Conclusions: Independent of R status, the PDVR group had lower overall survival and higher systemic recurrence rates. Full article

Despite expanded mental health services and outreach within the military, most active-duty members who endorse mental health problems do not seek services. Little is known about why this is the case, but cognitions may play a key role. In this study, cognitions relevant to service seeking were compared among three subgroups of active-duty members: those who endorse one or more mental health problems and sought services, those who endorse problems and do not seek services, and those who do not endorse problems. To examine differences and similarities among these groups, a stratified random sample of 162,340 was drawn from all active-duty members of the U.S. Department of the Air Force serving at 91 installations around the world. Each selected member was invited to anonymously complete the Air Force Community Assessment, and 63,227 members (39% of those invited) participated. Of these, one in five reported at least one mental health problem, and one in three reported receiving services within the past two years. Participants reporting problems and who had not sought services perceived more peer and institutional stigma, reported more knowledge and logistic barriers, reported more negative attitudes towards mental health services, and reported fewer attractors to mental health services compared with those who did not report problems. Those who reported problems and sought services reported more problems and more negative attitudes than those reporting problems who had not sought services. Nine of ten who reported problems but had not received services indicated they had no intention to seek them. Full article

Preclinical evidence suggests that short chain fatty acids (SCFAs) produced by gut microbiota may impact body composition and muscle growth. While aging is implicated in negative alterations to the gut microbiome, exercise may mitigate these changes. Limited human evidence indicates that resistance training (RT) does not appreciably alter the gut microbiome in older adults, and no human study has examined whether resistance training differentially alters the gut microbiome and associated SCFAs between younger and older individuals. Therefore, we examined whether 10 weeks of RT differentially altered fecal microbiota composition, fecal and circulating SCFAs, and serum markers associated with gastrointestinal integrity in two cohorts of adults. Fecal and serum samples were obtained from untrained younger (22 ± 2 years, n = 12) and older (58 ± 8 years, n = 12) participants prior to and following 10 weeks of supervised twice-weekly full-body RT. Outcome measures immediately before (PRE) and after the intervention (POST) included dual X-ray absorptiometry for body composition, ultrasound for vastus lateralis (VL) thickness, 16S rRNA gene sequencing fecal microbiome data, serum and fecal SCFAs measured by gas chromatography, and serum intestinal fatty acid-binding protein 2 (FABP2), lipopolysaccharide-binding protein (LBP), and leucine-rich alpha-2 glycoprotein (LRG-1) quantified by enzyme-linked immunosorbent assays. Main effects and interactions were measured by repeated measures analysis of variance (group × time; G × T) for all dependent variables, and Spearman correlations were used to explore relationships among changes in relevant outcomes. The intervention significantly increased VL thickness and lean body mass (p < 0.05) equally in both groups. Although group differences in microbiome beta diversity were identified, no effects of age, time, or their interaction were observed for the alpha diversity measures. Seven SCFAs were detected in the fecal samples, albeit no significant age, time, or interaction effects were evident. In serum, acetic acid was the only SCFA detected, with no significant age, time, or interaction effects. Serum LRG1 decreased for all participants (p = 0.007) with higher levels in younger adults (p = 0.015), but no G × T interactions were observed for this marker, serum FABP2, or LBP. No significant correlations were observed among RT-induced changes in muscle mass-related outcomes and changes in fecal microbiome diversity, total or individual SCFAs, or serum FABP2/LBP/LRG-1. These results highlight that 10 weeks of RT largely does not affect fecal microbiota, associated SCFAs, or select markers of gastrointestinal integrity in untrained younger or older adults. Full article

Agents that target the amyloid-β (Aβ) peptide associated with Alzheimer’s disease have seen renewed interest following the clinical success of antibody therapeutics. Small molecules, specifically metal-based complexes, are excellent candidates for advancement, given their relative ease of preparation and modular scaffold. Herein, several ruthenium–arene complexes containing 2,2-bipyridine (bpy) ligands were prepared and evaluated for their respective ability to modulate the aggregation of Aβ. This was carried out using the three sequential methods of thioflavin T (ThT) fluorescence, dynamic ligand scattering (DLS), and transmission electron microscopy (TEM). Overall, it was observed that RuBA, the complex with a 4,4-diamino-2,2-bipyridine ligand, had the greatest impact on Aβ aggregation. Further evaluation of the complexes was performed to determine their relative affinity for serum albumin and biocompatibility towards two neuronal cell lines. Ultimately, RuBA outperformed the other Ru complexes, where the structure–activity relationship codified the importance of the amino groups on the bpy for anti-Aβ activity. Full article

Background/Objectives: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. Methods: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample t-testing was used to identify mutations statistically associated with iBMV (p < 0.1). A value of +1 was assigned to each mutation with a positive association (“deleterious genes”), and a value of −1 to each with an inverse association (“protective genes”). The sum of these values was calculated to define iBMV risk scores of −1, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. Results: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. “Deleterious genes” included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; “protective genes” included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and −1, predicted an 88%, 61% and 65% likelihood of developing a BM (p < 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. −1, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and −1 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (p < 0.02). Conclusions: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules. Full article