Posthumous Resilience and Active Withdrawal: Byronic Contemplation of Violence and Vulnerabilities in the Anthropocene Embodied in the Sculpture of the Dying Gaul

This paper focuses upon the famous sculpture of the Dying Gaul, situated in the Capitoline Museum in Rome, in order to read and to rethink discourses of resilience in the Anthropocene. The Anthropocene poses fundamental questions to understandings of ‘bouncing back’ or imaginaries of ‘sustainable futures’. There can be no affirmative futural imaginaries if saving the world requires the destruction and sacrifice of innumerable others. Thinking with Byron’s reflections upon the Dying Gaul enables us to approach resilience from a radically different perspective, one that (read in conjunction with the work of Claire Colebrook, Karen Barad, Christina Sharpe, Dionne Brand and Saidiya Hartman amongst other contemporary theorists) we call a ‘posthumous’ approach. ‘Posthumous resilience’ refuses the lure of affirmation, of imaginaries of salvage and salvation, and instead seeks to generate an ethic of ‘active withdrawal’ that points beyond the temporal and spatial constraints of the colonial, imperial, imagination. We conclude with a reflection on how posthumous discourses of ‘active withdrawal’ can be the basis of generative politics of refusal which hold open conceptions of justice and seek to break from cycles of violence

A population-based study of children suggests blunted morning cortisol rhythms are associated with alterations of the systemic inflammatory state

Background: In children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis. Methods: The Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012–2017). Participants were 689 students in 4th grade (baseline; age=9.2 ± 0.4 years), and 647 students in 5th grade (age=10.5 ± 0.5 years). Nine salivary cortisol measures per child (2 awakening and 1 prior to bed for 3 sequential days) (n = 1336 child phenotype days; n = 7987 cortisol assays), 10 cytokines measured in morning and evening saliva samples (n = 202 child phenotype days), and lipids were measured. Clinical outcomes were blood pressure, weight and height (body mass index [BMI]; BMI = kg/m2), among others. Findings: Upon-waking cortisol levels were 0.28 ± 0.13 µg/dL, 30-minute post-waking 0.33 ± 0.15 µg/dL, and evening 0.08 ± 0.10 µg/dL. Salivary cytokine levels (n = 202) showed interleukins (IL) IL-1β and IL-8 were highest in early morning (upon awakening; AM), and IL-6 and tumor necrosis factor (TNF) TNF-α highest before bed (PM) (IL-1β AM \u3e PM [−4.02 fold; p \u3c 0.001]; IL-8 AM \u3e PM [−1.36 fold; p \u3c 0.001]; IL-6 AM \u3c PM [+1.49 fold; p \u3c 0.001]; TNF-α AM \u3c PM [+1.73 fold; p = 0.03]. Regression modeling showed high morning cortisol was associated with high morning IL-1β (p = 3.82 ×10−6), but low evening IL-1β (p = 6.27 ×10−4). Regression modeling of BMI z-score as the response variable showed the expected significant relationships to high density lipoprotein (HDL) (negative; p \u3c 0.001), mean arterial pressure (positive; p \u3c 0.001), and morning cortisol (negative; p = 0.01) but only weak relationships to either evening cortisol (p = 0.1) or cytokine (positive; p = 0.02; from the model with smallest Rsquared) levels. Interpretation: We provide preliminary data on diurnal fluctuations of inflammatory cytokines in saliva in a population-based cohort of children. Correlation of morning and evening cortisol levels with inflammatory cytokines in the same saliva samples showed that high morning cortisol was associated with high morning IL-1β and low evening IL-1β. Future studies may test the hypothesis that strong diurnal cycling of IL-1β may serve as a homeostatic mechanism keeping the immune system in check, and that low morning cortisol (possible circadian misalignment) may lead to less stringent control of inflammatory networks

Molecular identification of actinomycetes with antimicrobial, antioxidant and anticancer properties

The objectives of this study were to isolate and identify the actinomycetes strains from the soil and marine sediments and to evaluate the antimicrobial, antioxidant and cytotoxic activity of their bioactive secondary metabolites. Eight actinomycetes strains were isolated from soil and marine sediment samples collected from different areas in Egypt. Only three actinomycetes exhibited a wide spectrum of antimicrobial activities. They were active in vitro against microbial pathogen viz: Staphylococcus aureus, Escherichia coli, Salmonella typhi, Aspergillus parasiticus, Fusarium solani and Fusarium oxysporum. These promising isolates were selected and identified using molecular identification technique and identified as Streptomyces spp. The crude extracts from the three Streptomyces exhibited potent antimicrobial activities against a set of microbial pathogens as well as antioxidant and anticancer activity in human hepatocellular carcinoma cell line (HepG2). The crude extract of Streptomyces isolate D showed antitumor activity with lC50 0.85 µg/ mL. Forty compounds were identified from the two most promising ethyl acetate extracts of culture broth of Streptomyces sp. (D-EGY) by Gas Chromatography-Mass Spectrometry analysis. It could be concluded that the streptomycetes isolated from the Egyptian environment are promising candidates as antimicrobial, antioxidant and anticancer.The objectives of this study were to isolate and identify the actinomycetes strains from the soil and marine sediments and to evaluate the antimicrobial, antioxidant and cytotoxic activity of their bioactive secondary metabolites. Eight actinomycetes strains were isolated from soil and marine sediment samples collected from different areas in Egypt. Only three actinomycetes exhibited a wide spectrum of antimicrobial activities. They were active in vitro against microbial pathogen viz: Staphylococcus aureus, Escherichia coli, Salmonella typhi, Aspergillus parasiticus, Fusarium solani and Fusarium oxysporum. These promising isolates were selected and identified using molecular identification technique and identified as Streptomyces spp. The crude extracts from the three Streptomyces exhibited potent antimicrobial activities against a set of microbial pathogens as well as antioxidant and anticancer activity in human hepatocellular carcinoma cell line (HepG2). The crude extract of Streptomyces isolate D showed antitumor activity with lC50 0.85 µg/ mL. Forty compounds were identified from the two most promising ethyl acetate extracts of culture broth of Streptomyces sp. (D-EGY) by Gas Chromatography-Mass Spectrometry analysis. It could be concluded that the streptomycetes isolated from the Egyptian environment are promising candidates as antimicrobial, antioxidant and anticancer

Identification of Pathway-Specific Serum Biomarkers of Response to Glucocorticoid and Infliximab Treatment in Children with Inflammatory Bowel Disease

Objective: Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial. Methods: We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed by quantitative real time PCR. Concordance of longitudinal changes between the groups was used to identify markers responsive to treatment. Bioinformatic analysis was used to build insight into mechanisms of changes in response to treatment. Results: We identified 18 proteins and three miRNAs responsive to both prednisone and infliximab. Eight markers that decreased are associated with inflammation and have gene promoters regulated by nuclear factor (NF)-κB. Several that increased are associated with resolving inflammation and tissue damage. We also identified six markers that appear to be steroid-specific, three of which have glucocorticoid receptor binding elements in their promoter region. Conclusions: Serum markers regulated by the inflammatory transcription factor NF-κB are potential candidates for pharmacodynamic biomarkers that, if correlated with later outcomes like endoscopic or histologic healing, could be used to monitor treatment, optimize dosing, and enhance drug development. The pharmacodynamic biomarkers identified here hold potential to improve both clinical care and drug development. Further studies are warranted to investigate these markers as early predictors of response, or possibly surrogate outcomes

Racial Disparities in Patients with Stage IIIC Endometrial Cancer

Purpose/Objective(s): To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma (EC). Materials/Methods: A retrospective multi-institutional cohort study was conducted across 13 Northern American academic centers and included patients with stage IIIC endometrial carcinoma (EC) who received both chemotherapy and radiation in an adjuvant setting. Overall survival (OS) and recurrence-free survival (RFS) were calculated by Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. Propensity score matching was used to estimate the effect of race on survival outcomes. Statistical analyses were conducted using statistical software. Results: A total of 90 Black and 568 non-Black patients (83%) were identified with a median age at diagnosis of 62 (Interquartile Range (IQR) 55-70). Median follow-up was 45.3 months (IQR 24-71 months). Black patients were significantly older (p\u3c0.0001), had significantly more non-endometrioid histology (p\u3c0.0001), grade 3 tumors (p\u3c0.0001) and were more likely to have \u3e1 positive paraaortic lymph nodes (PALN) compared to non-black patients. The presence of lymphovascular space invasion (LVSI), depth of myometrial involvement, number of total nodes involved, adnexal and cervical involvement and stage were not correlated with race (all p\u3e0.1). As for treatment type, chemoradiotherapy sequencing approach was not correlated with race and no difference in number of chemotherapy cycles between Black and non-Black patients (p=0.32) was observed. Black patients were more often treated with external beam radiation therapy (EBRT) (43.3% and 24%, respectively) while a higher proportion of non-black patients received both EBRT and vaginal cuff brachytherapy (VBT) (65% vs. 38 %) (P\u3c0.0001) despite similar cervical involvement. The 5-year estimated OS and RFS rates were 45% and 47% compared to 77% and 68% for Black patients vs. non-black patients, respectively (p\u3c0.001). After propensity score matching, the 2 groups were well balanced for most of the covariates (age, histology, stage, grade, number of positive PALN, adnexal and cervical involvement) except for depth of myometrial invasion and radiation type. The estimated hazard ratios (HRs) of Black vs. non-Black patients were 1.613 (95% CI = (1.01, 2.575), p-value = 0.045) for OS and 1.487 (95% CI = (0.906, 2.440), p-value = 0.116) for RFS, indicating that Black patients have significantly worse OS. RFS differences did not reach statistical significance. Conclusion: Compared to non-Black patients, Black patients have higher rates of non-endometrioid histology, grade 3 tumors and number of PALNs. After propensity score matching, Black patients had worse OS but no statistically significant difference in RFS. Racial disparities could be mitigated by better access to care, equitable inclusion on randomized trials, and identification of genomic/molecular differences to better tailor adjuvant treatment

Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women

OBJECTIVE—Obesity is associated with endocrine abnormalities that predict the progression of insulin resistance to type 2 diabetes. Because skeletal muscle has been shown to secrete proteins that could be used as biomarkers, we characterized the secreted protein profile of muscle cells derived from extremely obese (BMI 48.8 ± 14.8 kg/m2; homeostasis model assessment [HOMA] 3.6 ± 1.0) relative to lean healthy subjects (BMI 25.7 ± 3.2 kg/m2; HOMA 0.8 ± 0.2)

The role of proteomics in defining the human embryonic secretome

Non-invasive gamete and embryo assessment is considered an important focus in assisted reproductive technologies (ART). Currently, the selection of embryos for transfer is based on morphological indices. Though successful, the field of ART would benefit from a non-invasive quantitative method of viability determination. Omics technologies, including transcriptomics, proteomics and metabolomics, have already begun providing evidence that viable gametes and embryos possess unique molecular profiles with potential biomarkers that can be utilized for developmental and/or viability selection. Unlike the human genome that is relatively fixed and steady throughout the human body, the human proteome, estimated at over a million proteins, is more complex, diverse and dynamic. It is the proteins themselves that contribute to the physiological homeostasis in any cell or tissue. Of particular interest in ART is the secretome, those proteins that are produced within the embryo and secreted into the surrounding environment. Defining the human embryonic secretome has the potential to expand our knowledge of embryonic cellular processes, including the complex dialogue between the developing embryo and its maternal environment, and may also assist in identifying those embryos with the highest implantation potential. Advances in proteomic technologies have allowed the non-invasive profiling of the human embryonic secretome with ongoing research focused on correlation with outcome. From a clinical perspective, embryo selection based on morphological assessment and non-invasive analysis of the human embryonic secretome may improve IVF success and lead to routine single embryo transfers