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Abstract In recent years, pharmaceutical counterfeiting has become an increasingly dangerous situation. A patient who unknowingly consumes a counterfeit drug is at a serious health risk. To address this problem, a low-cost and robust approach for authentication that can be administered at the point-of-care is required. Our proposed solution uses Optical Physical Unclonable Functions (PUFs); patterns formed by a stochastic process that can be used for authentication. We create edible PUFs (ePUFs) using electrospray deposition, which utilizes strong electric fields to atomize a liquid suspension into a plume of micro-scale droplets that are delivered to the target. The ePUFs are electrospray-deposited from an edible ink directly onto the surface of the drug tablets. The process parameters (flow rate, translation speed, and suspension concentration) govern the characteristics of the ePUF to provide highly stochastic patterns. To evaluate our approach, 200 ePUFs were deposited onto tablets at various conditions, followed by imaging and storage of the patterns in a database. For ePUF authentication, a machine vision approach was created using the open source SIFT pattern matching algorithm. Using optimized pattern-matching constraints, our algorithm was shown to be 100% successful in authenticating the cellphone images of the ePUFs to the database. Additionally, the algorithm was found to be robust against changes in illumination and orientation of the cellphone images.

ABSTRACTFungal infections cause a large health burden but are treated by only a handful of antifungal drug classes. Chromatin factors have emerged as possible targets for new antifungals. These targets include the reader proteins, which interact with posttranslationally modified histones to influence DNA transcription and repair. The YEATS domain is one such reader recognizing both crotonylated and acetylated histones. Here, we performed a detailed structure/function analysis of the Candida albicans YEATS domain reader Yaf9, a subunit of the NuA4 histone acetyltransferase and the SWR1 chromatin remodeling complex. We have previously demonstrated that the homozygous deletion mutant yaf9Δ/Δ displays growth defects and is avirulent in mice. Here we show that a YEATS domain mutant expected to inactivate Yaf9’s chromatin binding does not display strong phenotypes in vitro, nor during infection of immune cells or in a mouse systemic infection model, with only a minor virulence reduction in vivo. In contrast to the YEATS domain mutation, deletion of the C-terminal domain of Yaf9, a protein–protein interaction module necessary for its interactions with SWR1 and NuA4, phenocopies the null mutant. This shows that the C-terminal domain is essential for Yaf9 roles in vitro and in vivo, including C. albicans virulence. Our study informs on the strategies for therapeutic targeting of Yaf9, showing that approaches taken for the mammalian YEATS domains by disrupting their chromatin binding might not be effective in C. albicans, and provides a foundation for studying YEATS proteins in human fungal pathogens.IMPORTANCEThe scarcity of available antifungal drugs and rising resistance demand the development of therapies with new modes of action. In this context, chromatin regulation may be a target for novel antifungal therapeutics. To realize this potential, we must better understand the roles of chromatin regulators in fungal pathogens. Toward this goal, here, we studied the YEATS domain chromatin reader Yaf9 in Candida albicans. Yaf9 uses the YEATS domain for chromatin binding and a C-terminal domain to interact with chromatin remodeling complexes. By constructing mutants in these domains and characterizing their phenotypes, our data indicate that the Yaf9 YEATS domain might not be a suitable therapeutic drug target. Instead, the Yaf9 C-terminal domain is critical for C. albicans virulence. Collectively, our study informs how a class of chromatin regulators performs their cellular and pathogenesis roles in C. albicans and reveals strategies to inhibit them.

Abstract Circadian disruption increases cardiovascular disease (CVD) risk, through poorly understood mechanisms. Given that small RNA species are critical modulators of cardiac physiology/pathology, we sought to determine the extent to which cardiomyocyte circadian clock (CCC) disruption impacts cardiac small RNA species. Accordingly, we collected hearts from cardiomyocyte-specific Bmal1 knockout (CBK; a model of CCC disruption) and littermate control (CON) mice at multiple times of the day, followed by small RNA-seq. The data reveal 47 differentially expressed miRNAs species in CBK hearts. Subsequent bioinformatic analyses predict that differentially expressed miRNA species in CBK hearts influence processes such as circadian rhythmicity, cellular signaling, and metabolism. Of the induced miRNAs in CBK hearts, 7 are predicted to be targeted by the transcriptional repressors REV-ERBα/β (integral circadian clock components that are directly regulated by BMAL1). Similar to CBK hearts, cardiomyocyte-specific Rev-erbα/β double knockout (CM-RevDKO) mouse hearts exhibit increased let-7c-1-3p, miR-23b-5p, miR-139-3p, miR-5123, and miR-7068-3p levels. Importantly, 19 putative targets of these 5 miRNAs are commonly repressed in CBK and CM-RevDKO heart (of which 16 are targeted by let-7c-1-3p). These observations suggest that disruption of the circadian BMAL1–REV-ERBα/β regulatory network in the heart induces distinct miRNAs, whose mRNA targets impact critical cellular functions.

Despite their ubiquity, few have used traffic camera networks for social science research. Using 1,312,977 images collected from 768 London-based cameras leading up to the 2015 UK general election, this study not only demonstrates how traffic camera data can be used to effectively measure same-day turnout, but we also provide ways such data can be used to assess political behavior more broadly. Such automated enumeration is especially important in countries where official results are only returned for the current election, making it difficult for those interested in assessing turnout at lower levels of aggregation, even when those elections are next on the calendar. Although we are not the first to suggest the value of images-as-data, this study hopes to underline the importance of video-as-data, while simultaneously offering an important foundation for future research.

ObjectiveDuring the early stages of the COVID-19 pandemic, medical students were abruptly removed from clinical rotations and transitioned to virtual learning. This study investigates the impact of this shift on students’ wellbeing and preparedness for advanced training.MethodsThrough qualitative research methods, including semi-structured interviews, the experiences of medical students working on the COVID-19 frontline were explored.ResultsThe comprehensive findings of the study shed light on the profound emotional journey that medical students embarked upon during the relentless public health crisis. Within the chaos and overwhelming demands of the pandemic, medical students discovered a profound sense of purpose and fulfillment in their contributions to the welfare of the community. Despite the personal sacrifices they had to make, such as long hours, limited social interactions, and potentially risking their own health, students reported feelings of relief and gratitude.ConclusionTailored support systems for medical students’ wellbeing are crucial for improving healthcare delivery during crises. Medical schools should adopt a holistic curriculum approach, integrating interdisciplinary learning and prioritizing student wellbeing. Recognizing the pandemic’s impact on students and implementing targeted support measures ensures resilience and contributes to an improved healthcare system.

Abstract Background The radiometal gallium-68 (68Ga) is increasingly used in diagnostic positron emission tomography (PET), with 68Ga-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional 99mTc agents. In precision medicine, PET applications of 68Ga are widespread, with 68Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin. Main body These 68Ga radiopharmaceuticals include agents such as [68Ga]Ga-macroaggregated albumin for myocardial perfusion evaluation, [68Ga]Ga-PLED for assessing renal function, [68Ga]Ga-t-butyl-HBED for assessing liver function, and [68Ga]Ga-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (68Ge) generators and cyclotron production routes strongly positions 68Ga for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the 68Ga radiopharmaceutical community, and recommendations for centers interested in establishing 68Ga radiopharmaceutical production. Conclusion This review outlines important aspects of 68Ga radiopharmacy, including 68Ga production routes using a 68Ge/68Ga generator or medical cyclotron, standardized 68Ga radiolabeling methods, quality control procedures for clinical 68Ga radiopharmaceuticals, and suggested best practices for centers with established or upcoming 68Ga radiopharmaceutical production. Finally, an outlook on 68Ga radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community.

This article highlights recent developments of SPECT and PET diagnostic imaging surrogates for targeted alpha particle therapy (TAT) radiopharmaceuticals. It outlines the rationale for using imaging surrogates to improve diagnostic-scan accuracy and facilitate research, and the properties an imaging-surrogate candidate should possess. It evaluates the strengths and limitations of each potential imaging surrogate. Thirteen surrogates for TAT are explored: 133La, 132La, 134Ce/134La, and 226Ac for 225Ac TAT; 203Pb for 212Pb TAT; 131Ba for 223Ra and 224Ra TAT; 123I, 124I, 131I and 209At for 211At TAT; 134Ce/134La for 227Th TAT; and 155Tb and 152Tb for 149Tb TAT.

Many SARS-CoV-2 variants have emerged during the course of the COVID-19 pandemic. These variants have acquired mutations conferring phenotypes such as increased transmissibility or virulence, or causing diagnostic, therapeutic, or immune escape. Detection of Alpha and the majority of Omicron sublineages by PCR relied on the so-called S gene target failure due to the deletion of six nucleotides coding for amino acids 69–70 in the spike (S) protein. Detection of hallmark mutations in other variants present in samples relied on whole genome sequencing. However, whole genome sequencing as a diagnostic tool is still in its infancy due to geographic inequities in sequencing capabilities, higher cost compared to other molecular assays, longer turnaround time from sample to result, and technical challenges associated with producing complete genome sequences from samples that have low viral load and/or high background. Hence, there is a need for rapid genotyping assays. In order to rapidly generate information on the presence of a variant in a given sample, we have created a panel of four triplex RT-qPCR assays targeting 12 mutations to detect and differentiate all five variants of concern: Alpha, Beta, Gamma, Delta, and Omicron. We also developed an expanded pentaplex assay that can reliably distinguish among the major sublineages (BA.1–BA.5) of Omicron. In silico, analytical and clinical testing of the variant panel indicate that the assays exhibit high sensitivity and specificity. This panel can help fulfill the need for rapid identification of variants in samples, leading to quick decision making with respect to public health measures, as well as treatment options for individuals. Compared to sequencing, these genotyping PCR assays allow much faster turn-around time from sample to results—just a couple hours instead of days or weeks.

The COVID-19 pandemic caused complex and enduring challenges for healthcare providers and medical educators. The rapid changes to the medical education landscape forced universities across the world to pause traditional medical training. In Basel, Switzerland, however, medical students had the opportunity to work on the COVID-19 frontlines. Our purpose was to understand how they perceived both learning and professional identity development in this novel context. We conducted semi-structured interviews with 21 medical students who worked in a COVID-19 testing facility at the University Hospital of Basel. Using constructivist grounded theory methodology, we collected and analyzed data iteratively using the constant comparative approach to develop codes and theoretical themes. Most participants perceived working on the pandemic frontlines as a positive learning experience, that was useful for improving their technical and communication skills. Participants particularly valued the comradery amongst all team members, perceiving that the hierarchy between faculty and students was less evident in comparison to their usual learning environments. Since medical students reported that their work on the pandemic frontlines positively affected their learning, the need to create more hands-on learning opportunities for medical students challenges curriculum developers. Medical students wish to feel like full-fledged care team members rather than observing sideliners. Performing simple clinical tasks and collaborative moments in a supportive learning environment may promote learning and professional development and should be encouraged in the post-pandemic era.

Abstract This study reports the high-yield production of a novel 133/135La theranostic pair at a 22 MeV proton beam energy as an attractive alternative to the recently introduced 132/135La pair, demonstrating over an order of magnitude production increase of 133/135La (231 ± 8 MBq 133La and 166 ± 5 MBq 135La at End of Bombardment (EOB)) compared to 11.9 MeV production of 132/135La (0.82 ± 0.06 MBq 132La and 19.0 ± 1.2 MBq 135La) for 500 µA·min irradiations. A new sealed solid cyclotron target is introduced, which is fast to assemble, easy to handle, storable, and contains reusable components. Radiolabeling with macrocyclic chelators DOTA and macropa achieved full incorporation, with respective apparent 133La molar activites of 33 ± 5 GBq/µmol and 30 ± 4 GBq/µmol. PET centers with access to a 22 MeV capable cyclotron could produce clinically-relevant doses of 133/135La, via natBa irradiation, as a standalone theranostic agent for PET imaging and Auger electron therapy. With lower positron energies and less energetic and abundant gamma rays than 68Ga, 44Sc and 132La, 133La appears to be an attractive radiometal candidate for PET applications requiring a higher scanning resolution, a relatively long isotopic half-life, ease of handling, and a low patient dose.

BackgroundFunctional recovery in psychosis remains a challenge despite current evidence-based treatment approaches. To address this problem, innovative interventions using virtual reality (VR) have recently been developed. VR technologies have enabled the development of realistic environments in which individuals with psychosis can receive psychosocial treatment interventions in more ecological settings than traditional clinics. These interventions may therefore increase the transfer of learned psychosocial skills to real-world environments, thereby promoting long-term functional recovery. However, the overall feasibility and efficacy of such interventions within the psychosis population remain unclear. ObjectiveThis systematic review aims to investigate whether VR-based psychosocial interventions are feasible and enjoyable for individuals with psychosis, synthesize current evidence on the efficacy of VR-based psychosocial interventions for psychosis, and identify the limitations in the current literature to guide future research. MethodsThis research followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Literature searches were conducted in PubMed and PsycINFO in May 2021. We searched for peer-reviewed English articles that used a psychosocial intervention with a VR component. Participants in the included studies were diagnosed with schizophrenia, schizoaffective disorder, or another psychotic disorder. The included studies were divided into four categories as follows: cognitive remediation interventions, social skills interventions, vocational skills interventions, and auditory verbal hallucinations and paranoia interventions. The risk of bias assessment was performed for each study. ResultsA total of 18 studies were included in this systematic review. Of these 18 studies, 4 (22%) studies used a cognitive remediation intervention, 4 (22%) studies used a social skills intervention, 3 (17%) studies used a vocational skills intervention, and 7 (39%) studies implemented an intervention aimed at improving auditory verbal hallucinations or paranoia. A total of 745 individuals with psychosis were included in the study. All the studies that evaluated feasibility showed that VR-based psychosocial interventions were feasible and enjoyable for individuals with psychosis. The preliminary evidence on efficacy included in this review suggests that VR-based psychosocial interventions can improve cognitive, social, and vocational skills in individuals with psychosis. VR-based interventions may also improve the symptoms of auditory verbal hallucinations and paranoia. The skills that participants learned through these interventions were durable, transferred into real-world environments, and led to improved functional outcomes, such as autonomy, managing housework, and work performance. ConclusionsVR-based interventions may represent a novel and efficacious approach for improving psychosocial functioning in psychosis. Therefore, VR-based psychosocial interventions represent a promising adjunctive therapy for the treatment of psychosis, which may be used to improve psychosocial skills, community functioning, and quality of life.

The synthesis and structural properties of a series of chromium tricarbonyl `piano-stool' complexes bearing substituted pentafulvene ligands were studied. The complexes, tricarbonyl(1,3,6-triphenylfulvene)chromium(0) benzene hemisolvate, [Cr(C24H18)(CO)3]·0.5C6H6 (I), tricarbonyl[1,3-diphenyl-6-(3-vinylphenyl)fulvene]chromium(0), [Cr(C26H20)(CO)3] (II), and tricarbonyl[1,3-diphenyl-6-(pyren-1-yl)fulvene]chromium(0), [Cr(C34H22)(CO)3] (III), each have a distorted octahedral geometry, with the fulvene coordinated in a π–η2:π–η2:π–η2 fashion. Significant deviation of the exocyclic fulvene double bond from the cyclopentadiene plane accompanies coordination. Evidence of non-covalent π–π interactions was observed in both (I) and (III), with centroid-to-centroid distances ranging from 3.330 (8) to 3.494 (8) Å.

This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinical trials; and an outlook on the future of TAT.

Spinal cord injury (SCI) initiates a severe, destructive inflammation with pro-inflammatory, CD68+/CD163−, phagocytic macrophages infiltrating the area of necrosis and hemorrhage by day 3 and persisting for the next 16 weeks. Inhibition of macrophage infiltration of the site of necrosis that is converted into a cavity of injury (COI) during the first week post-SCI, should limit inflammatory damage, shorten its duration and result in neuroprotection. By sustained subdural infusion we administered Serp-1, a Myxoma virus-derived immunomodulatory protein previously shown to improve neurologic deficits and inhibit macrophage infiltration in the COI in rats with the balloon crush SCI. Firstly, in a 7 day long study, we determined that the optimal dose for macrophage inhibition was 0.2 mg/week. Then, we demonstrated that a continuous subdural infusion of Serp-1 for 8 weeks resulted in consistently accelerated lowering of pro-inflammatory macrophages in the COI and in their almost complete elimination similar to that previously observed at 16 weeks in untreated SCI rats. The macrophage count in the COI is a quantitative test directly related to the severity of destructive inflammation initiated by the SCI. This test has consistently demonstrated anti-inflammatory effect of Serp-1 interpreted as neuroprotection, the first and necessary step in a therapeutic strategy in neurotrauma.

Faba bean (Vicia faba Roth) and pea (Pisum sativum L.) are grown worldwide as protein sources for food and feed and can be used as cover crops after wheat (Triticum aestivum L.). However, faba bean is underutilized in upper Midwest farming systems. This study was conducted to determine how faba bean relates to pea as a forage, cover crop, and in cycling of nutrients to maize (Zea mays L.) in the following season. Five faba bean cultivars and two pea cultivars, a forage pea and a field pea, were established after wheat harvest in North Dakota, in 2017 and 2018. Faba bean and pea cultivars averaged 1.3 Mg ha−1 of biomass, enough to support 1.5 animal unit month (AUM) ha−1 for a 450 kg cow (Bos taurus L.) with calf, at 50% harvest efficiency. Crude protein content was highest in faba bean cv. Boxer (304 g kg−1), with faba bean cv. Laura and forage pea cv. Arvika having similar content, and field pea having the least (264 g kg−1). Cover crop treatments did not affect maize in the following year, indicating no nutrient cycling from faba bean and pea to maize. Both cover crop species tested provided high protein forage, suitable for late grazing, with a more fibrous crop residue. Faba bean has potential as a cover crop in the upper Midwest while providing greater quality forage than pea.

Twelve wild North American porcupines (Erethizon dorsatum) out of a total of 44 of this species examined in an 8-year period were diagnosed with dermatopathies while being cared for at two wildlife rehabilitation clinics. Biopsy and necropsy were performed on seven and five animals, respectively. Atypical dermatophytosis was diagnosed in all cases. Lesions consisted of diffuse severe epidermal hyperkeratosis and mild hyperplasia with mild lymphoplasmacytic dermatitis and no folliculitis. Dermatophytes were noted histologically as hyphae and spores in hair shafts, and follicular and epidermal keratin. Trichophyton sp. was grown in 5/6 animals where culture was performed, with a molecular diagnosis of Arthroderma benhamiae/Trichophyton mentagrophytes in these five cases. Metagenomic analysis of formalin-fixed paraffin-embedded tissue samples from three cases identified fungi from 17 orders in phyla Basidiomycota and Ascomycota. Alteration of therapy from ketaconazole, which was unsuccessful in four out of five early cases, to terbinafine or nitraconazole led to the resolution of disease and recovery to release in four subsequent animals. In all, six animals were euthanized or died due to dermatopathy, no cases resolved spontaneously, and six cases were resolved with therapy. The work we present demonstrates an atypical lesion and anatomical distribution due to dermatophytosis in a series of free-ranging wild porcupines and the successful development of novel techniques for extracting and sequencing nucleic acids from fungus in archival formalin-fixed paraffin-embedded animal tissue.

M Bauer,1 J Bryce,2 P Hadji11University of Marburg, Marburg, Germany; 2National Cancer Institute, Naples, ItalyAbstract: Postmenopausal women have an increased risk of osteopenia and osteoporosis due to loss of the bone-protective effects of estrogen. Disease-related processes may also contribute to the risk of bone loss in postmenopausal women with breast cancer. One of the most common and severe safety issues associated with cancer therapy for patients with breast cancer is bone loss and the associated increase in risk of fractures. This paper reviews the recent literature pertaining to aromatase inhibitor (AI)-associated bone loss, and discusses suggested management and preventative approaches that may help patients remain on therapy to derive maximum clinical benefit. A case study is presented to illustrate the discussion. We observed that AIs are in widespread use for women with hormone receptor-positive breast cancer and are now recommended as adjuvant therapy, either as primary therapy or sequential to tamoxifen, for postmenopausal women. AIs target the estrogen biosynthetic pathway and deprive tumor cells of the growth-promoting effects of estrogen, and AI therapies provide benefits to patients in terms of improved disease-free survival. However, there is a concern regarding the increased risk of bone loss with prolonged AI therapy, which can be managed in many cases with the use of bisphosphonates and other interventions (eg, calcium, vitamin D supplementation, exercise).Keywords: aromatase inhibitors, bisphosphonates, bone loss, breast cancer, estrogen

Jane Bryce1, Martina Bauer2, Peyman Hadji21National Cancer Institute, Naples, Italy; 2Philipps University of Marburg, Marburg, GermanyBackground: In order to reduce the risk of recurrence, adjuvant treatment with an aromatase inhibitor (AI) is recommended for postmenopausal women following surgery for hormone receptor-positive breast cancer. AIs are associated with improved disease-free survival compared with tamoxifen. The adverse events associated with AIs resemble those of menopause, such as bone density loss and musculoskeletal symptoms.Purpose: We examine the case of a postmenopausal woman who was prescribed anastrozole, a nonsteroidal AI, as adjuvant therapy following surgery for estrogen and progesterone receptor-positive (ER and PgR+) breast cancer.Methods and sample: A 58-year-old postmenopausal woman diagnosed with ER and PgR+ breast cancer was prescribed anastrozole as adjuvant therapy following a right-inferior quadrantectomy. After experiencing joint pain and stiffness, she was prescribed paracetamol and a topical nonsteroidal anti-inflammatory drug. She was also counseled on nonpharmacological interventions. However, she continued to experience symptoms, and reported that she was not taking anastrozole regularly.Results: The case study patient ultimately found relief by switching to letrozole, another aromatase inhibitor. This approach is supported by recent studies examining the benefits of switching strategies between aromatase inhibitors in order to relieve symptoms of arthralgia/myalgia.Conclusions: Both adherence and strategies for managing aromatase inhibitor-associated arthralgia are key to deriving maximal clinical benefit from AI therapy. Switching from one aromatase inhibitor to another may provide a viable option in managing adverse events and enhancing adherence to medication.Keywords: adherence, anastrozole, aromatase inhibitor, arthralgia, breast cancer, letrozole

OBJECTIVE: The multi-country evaluation of Integrated Management of Childhood Illness (IMCI) effectiveness, cost and impact (MCE) is a global evaluation to determine the impact of IMCI on health outcomes and its cost-effectiveness. MCE studies are under way in Bangladesh, Brazil, Peru, Uganda and the United Republic of Tanzania. The objective of this analysis from the Bangladesh MCE study was to describe the quality of care delivered to sick children under 5 years old in first-level government health facilities, to inform government planning of child health programmes. METHODS: Generic MCE Health Facility Survey tools were adapted, translated and pre-tested. Medical doctors trained in IMCI and these tools conducted the survey in all 19 health facilities in the study areas. The data were collected using observations, exit interviews, inventories and interviews with facility providers. FINDINGS: Few of the sick children seeking care at these facilities were fully assessed or correctly treated, and almost none of their caregivers were advised on how to continue the care of the child at home. Over one-third of the sick children whose care was observed were managed by lower-level workers who were significantly more likely than higher-level workers to classify the sick child correctly and to provide correct information on home care to the caregiver. CONCLUSION: These results demonstrate an urgent need for interventions to improve the quality of care provided for sick children in first-level facilities in Bangladesh, and suggest that including lower-level workers as targets for IMCI case-management training may be beneficial. The findings suggest that the IMCI strategy offers a promising set of interventions to address the child health service problems in Bangladesh.

OBJECTIVES/SPECIFIC AIMS: This study will assess the effect of essential amino acid (EAA) supplementation on plasma triglyceride (TG) in elderly adults. We will also explore the mechanisms mediating EAA mediated changes in fat metabolism and to suggest promising routes to refine therapy of hypertriglyceridemia. METHODS/STUDY POPULATION: In total, 7 nondiabetic male and female subjects ages 50–75 years with elevated plasma TG levels (130–500 mg/dL) were recruited to participate in an acute (5 h) and long-term (8 wk) EAA supplementation study. We measured changes in regional and whole body fat metabolism, including changes in body composition, plasma TG levels, whole body fat metabolic rates, tissue mitochondrial respiratory capacity, and metabolomic profiles before and after supplementation. RESULTS/ANTICIPATED RESULTS: Long-term EAA supplementation decreased fasted plasma TG levels by 19% (p

BackgroundThe microenvironment plays a pivotal role in tumor cell proliferation, survival and migration. Invasive cancer cells face a new set of environmental challenges as they breach the basement membrane and colonize distant organs during the process of metastasis. Phenotypic switching, such as that which occurs during epithelial-mesenchymal transition (EMT), may be associated with a remodeling of cell surface receptors and thus altered responses to signals from the tumor microenvironment.Methodology/principal findingsWe assessed changes in intracellular Ca(2+) in cells loaded with Fluo-4 AM using a fluorometric imaging plate reader (FLIPR(TETRA)) and observed significant changes in the potency of ATP (EC(50) 0.175 µM (-EGF) versus 1.731 µM (+EGF), PConclusionsThe acquisition of a new suite of cell surface purinergic receptors is a feature of EGF-mediated EMT in MDA-MB-468 breast cancer cells. Such changes may impart advantageous phenotypic traits and represent a novel mechanism for the targeting of cancer metastasis.