Ethylene glycol dinitrate (EGDN) is a nitrate ester explosive widely used in military ordnance and missile systems. This study investigates the decomposition dynamics of the EGDN cation using a comprehensive approach that combines femtosecond time-resolved mass spectrometry (FTRMS) experiments with electronic structure and molecular dynamics computations. We identify three distinct dissociation time scales for the metastable EGDN cation of approximately 40-60 fs, 340-450 fs, and >2 ps.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2024
Neutrophils, the most abundant leukocytes in human peripheral circulation, are crucial for the innate immune response. They are typically quiescent but rapidly activate in response to infection and inflammation, performing diverse functions such as oxidative burst, phagocytosis, and NETosis, which require significant metabolic adaptation. Deeper insights into such metabolic changes will help identify regulation of neutrophil functions in health and diseases.
View Article and Find Full Text PDFHepatic hydrothorax (HH) refers to the presence of a pleural effusion that develops in the context of underlying liver cirrhosis and portal hypertension. It carries a high risk of morbidity and mortality, with a median survival of 8-12 months. Diagnosis is usually confirmed by pleural aspiration, demonstrating typical features of a transudative effusion in the absence of co-existent cardio-pulmonary or renal pathology.
View Article and Find Full Text PDFCryptococcosis, a fungal infection primarily caused by (CN), is a significant concern for immunocompromised individuals. This paper presents a case of a 51-year-old immunocompromised male who initially presented with symptoms suggestive of community-acquired pneumonia but was later diagnosed with pulmonary cryptococcosis caused by capsule-deficient CN. The patient's exposure to construction dust, coupled with his immunocompromised state due to immunosuppressive treatment for psoriatic arthritis, likely contributed to his susceptibility.
View Article and Find Full Text PDFNeutrophils - the first responders in innate immunity - perform a variety of effector functions associated with specific metabolic demand. To maintain fitness and support functions, neutrophils have been found to utilize extracellular glucose, intracellular glycogen, and other alternative substrates. However, the quantitative contribution of these nutrients under specific conditions and the relative dependence of various cell functions on specific nutrients remain unclear.
View Article and Find Full Text PDFPlants rely on cross-resistance traits to defend against multiple, phylogenetically distinct enemies. These traits are often the result of long co-evolutionary histories. Biological invasions can force naïve plants to cope with novel, coincident pests, and pathogens.
View Article and Find Full Text PDFObjective: This study examines childhood and clinical factors theorized to impact therapeutic alliance development over the course of psychotherapy.
Method: Raters assessed the therapeutic alliance of 212 client-therapist dyads, participating in two randomized controlled trials of schema therapy and cognitive behavioural therapy for binge eating or major depression, at three time points. Linear mixed models were used to characterize therapeutic alliance development over time and assess the influence of childhood trauma, perceived parental bonding, diagnosis and therapy type on scores.
The gut microbiota regulates multiple facets of host metabolism and immunity through the production of signaling metabolites, such as polyamines which are small organic compounds that are essential to host cell growth and lymphocyte activation. Polyamines are most abundant in the intestinal lumen, where their synthesis by the gut microbiota is influenced by microbiome composition and host diet. Disruption of the host gut microbiome in metabolic syndrome and obesity-related type 2 diabetes (obesity/T2D) results in potential dysregulation of polyamine synthesis.
View Article and Find Full Text PDFObjective: Current evidence indicates treatment for adults with anorexia nervosa (AN) requires improvement given recovery rates are low to moderate, and relapse rates are high. Metacognitive therapy (MCT) is an effective treatment for anxiety and depressive disorders. This study evaluates if MCT can be successfully modified to treat AN in a naturalistic clinical setting.
View Article and Find Full Text PDFObjective: Although personality traits have been found to be associated with body dissatisfaction for women in the general population, little research has explored these associations for people with eating disorders. Furthermore, it is unknown whether these associations are direct or are mediated by other factors. In this cross-sectional study, secondary analyses of data from two clinical trials were conducted to determine which personality dimensions contributed to body dissatisfaction in women with bulimia nervosa, and whether low self-esteem and depression mediate these associations independently or in serial.
View Article and Find Full Text PDFNeutrophils are cells at the frontline of innate immunity that can quickly activate effector functions to eliminate pathogens upon stimulation. However, little is known about the metabolic adaptations that power these functions. Here we show rapid metabolic alterations in neutrophils upon activation, particularly drastic reconfiguration around the pentose phosphate pathway, which is specifically and quantitatively coupled to an oxidative burst.
View Article and Find Full Text PDFThe function of macrophages in vitro is linked to their metabolic rewiring. However, macrophage metabolism remains poorly characterized in situ. Here, we used two-photon intensity and lifetime imaging of autofluorescent metabolic coenzymes, nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), to assess the metabolism of macrophages in the wound microenvironment.
View Article and Find Full Text PDFIntroduction: A major focus of interstitial lung disease (ILD) has centered on disorders termed idiopathic interstitial pneumonias (IIPs) which include, among others, idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, and respiratory bronchiolitis-interstitial lung disease.
Areas Covered: We review the radiologic and histologic patterns for the nine disorders classified by multidisciplinary approach as IIP, and describe the remarkable amount of published epidemiologic, translational, and molecular studies demonstrating their associations with numerous yet definitive environmental exposures, occupational exposures, pulmonary diseases, systemic diseases, medication toxicities, and genetic variants.
Expert Opinion: In the 21st century, these disorders termed IIPs are rarely idiopathic, but rather are well-described radiologic and histologic patterns of lung injury that are associated with a wide array of diverse etiologies.
Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local and distant metastasis and disease relapse are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild-type HN30 and p53 mutant HN12 head and neck cancer models.
View Article and Find Full Text PDFTransmembrane protein engulfment receptors expressed on the surface of phagocytes engage ligands on apoptotic cells and debris to initiate a sequence of events culminating in material internalization and immunologically beneficial outcomes. Engulfment receptors are modular, comprised of functionally independent extracellular ligation domains and cytosolic signaling motifs. Cognate kinases, adaptors, and phosphatases regulate engulfment by controlling the degree of receptor activation in phagocyte plasma membranes, thus acting as receptor-proximal signaling modules.
View Article and Find Full Text PDFBackground: Multidisciplinary discussion (MDD) is widely recommended for patients with interstitial lung disease (ILD), but published primary data from MDD has been scarce, and factors influencing MDD other than chest computed tomography (CT) and lung histopathology interpretations have not been well-described.
Methods: Single institution MDD of 179 patients with ILD.
Results: MDD consensus clinical diagnoses included autoimmune-related ILD, chronic hypersensitivity pneumonitis, smoking-related ILD, idiopathic pulmonary fibrosis, medication-induced ILD, occupation-related ILD, unclassifiable ILD, and a few less common pulmonary disorders.
The contribution of the apple microbiome to the production chain of apple was so far largely unknown. Here, we describe the apple fruit microbiome and influences on its composition by parameters such as storage season, storage duration, storage technology, apple variety, and plant protection schemes. A combined culturing and metabarcoding approach revealed significant differences in the abundance, composition, and diversity of the apple fruit microbiome.
View Article and Find Full Text PDFBackground: Although anterior cruciate ligament (ACL) injuries are common in female soccer players, the optimal graft option for ACL reconstruction is currently unclear.
Purpose/hypothesis: To compare the outcomes of female soccer players after ACL reconstruction using either hamstring tendon autograft or bone-patellar tendon-bone (BTB) autograft. We hypothesized that there would be no difference in clinical outcome scores, return to sport, or retear rates between BTB and hamstring grafts in our study cohort.
Background: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Centers for Medicare and Medicaid Services pledged payment for telehealth visits for the duration of this public health emergency in an effort to decrease COVID-19 transmission and allow for deployment of residents and attending physicians to support critical-care services. Although the COVID-19 pandemic has vastly expanded telehealth use, no studies to our knowledge have analyzed the implementation and success of telehealth for orthopaedic trauma. This population is unique in that patients who have experienced orthopaedic trauma range in age from early childhood to late adulthood, they vary across the socioeconomic spectrum, may need to undergo emergent or urgent surgery, often have impaired mobility, and, historically, do not always follow-up consistently with healthcare providers.
View Article and Find Full Text PDFGlucose is catabolized by two fundamental pathways, glycolysis to make ATP and the oxidative pentose phosphate pathway to make reduced nicotinamide adenine dinucleotide phosphate (NADPH). The first step of the oxidative pentose phosphate pathway is catalyzed by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here we develop metabolite reporter and deuterium tracer assays to monitor cellular G6PD activity.
View Article and Find Full Text PDFIn response to signals associated with infection or tissue damage, macrophages undergo a series of dynamic phenotypic changes. Here we show that during the response to LPS and interferon-γ stimulation, metabolic reprogramming in macrophages is also highly dynamic. Specifically, the TCA cycle undergoes a two-stage remodeling: the early stage is characterized by a transient accumulation of intermediates including succinate and itaconate, while the late stage is marked by the subsidence of these metabolites.
View Article and Find Full Text PDFImmune cells are capable of sensing various signals in the microenvironment and turning on specific immune functions in response. The appropriate transition of immune cells into diverse functional states, which is crucial for immunity, involves complex and well-regulated changes in transcriptional program. Accumulating evidence shows that epigenetic remodeling plays a central role in mediating the transcriptional program for immune cell activation and immunological memory.
View Article and Find Full Text PDFJBJS Case Connect
December 2019
Case: A 62-year-old man presented with a posterolateral knee dislocation sustained in a motorcycle collision initially managed nonsurgically. His treatment was complicated by recurrent dislocation from noncompliance with bracing and weight-bearing restrictions and by comorbidities including peripheral artery disease, type 2 diabetes, and heavy smoking and drinking. He was treated with a multiplanar knee-spanning external fixator and patellar tendon repair without further ligamentous reconstruction.
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