Metabolomics Fingerprint Predicts Risk of Death in Dilated Cardiomyopathy and Heart Failure

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Metabolomics may help refine risk assessment and potentially guide HF management, but dedicated studies are few. This study aims at stratifying the long-term risk of death in a cohort of patients affected by HF due to dilated cardiomyopathy (DCM) using serum metabolomics via nuclear magnetic resonance (NMR) spectroscopy. METHODS: A cohort of 106 patients with HF due to DCM, diagnosed and monitored between 1982 and 2011, were consecutively enrolled between 2010 and 2012, and a serum sample was collected from each participant. Each patient underwent half-yearly clinical assessments, and survival status at the last follow-up visit in 2019 was recorded. The NMR serum metabolomic profiles were retrospectively analyzed to evaluate the patient's risk of death. Overall, 26 patients died during the 8-years of the study. RESULTS: The metabolomic fingerprint at enrollment was powerful in discriminating patients who died (HR 5.71, p = 0.00002), even when adjusted for potential covariates. The outcome prediction of metabolomics surpassed that of N-terminal pro b-type natriuretic peptide (NT-proBNP) (HR 2.97, p = 0.005). Metabolomic fingerprinting was able to sub-stratify the risk of death in patients with both preserved/mid-range and reduced ejection fraction [hazard ratio (HR) 3.46, p = 0.03; HR 6.01, p = 0.004, respectively]. Metabolomics and left ventricular ejection fraction (LVEF), combined in a score, proved to be synergistic in predicting survival (HR 8.09, p = 0.0000004). CONCLUSIONS: Metabolomic analysis via NMR enables fast and reproducible characterization of the serum metabolic fingerprint associated with poor prognosis in the HF setting. Our data suggest the importance of integrating several risk parameters to early identify HF patients at high-risk of poor outcomes

The significance of proline-rich tyrosine kinase2 (Pyk2) on hepatocellular carcinoma progression and recurrence

Understanding the precise molecular mechanisms that trigger liver cancer cell migration and invasion could develop novel therapeutic strategies targeting cancer cell invasion to increase the sensitivity to current treatment modalities. In the current study, 49 patients with hepatocellular carcinoma (HCC) were included prospectively. Liver tumour and adjacent non-tumour tissues were detected for the expression of Proline-rich tyrosine kinase 2 (Pyk2), focal adhesion kinase (FAK), ezrin and fibronectin at protein and/or gene levels. Correlation between the expressions of Pyk2/FAK with the clinical pathological data was analysed. Protein expression of Pyk2 was also examined in a nude mice orthotopic liver tumour model with higher metastatic potential. There were 59% (29 out of 49) and 57% (28 out of 49) of HCC patients with higher levels of Pyk2 and FAK protein/gene expression, respectively. We observed a positive correlation between the protein and gene expression levels of Pyk2 and FAK (P=0.000, r=0.875). Overexpression of Pyk2 and FAK was significantly correlated with shorter disease-free survival. Patients with higher levels of Pyk2/FAK had larger tumour size and advanced Edmonson grading. In the animal studies, Pyk2 overexpression was found in infiltrative tumour cells and lung metastatic nodules. In conclusion, overexpression of Pyk2 and FAK was found in nearly 60% of HCC patients and was significantly correlated with poor prognosis. The significance of Pyk2 in HCC invasiveness was confirmed by animal studies. © 2007 Cancer Research UK.published_or_final_versio

Defective Peripheral Nerve Development Is Linked to Abnormal Architecture and Metabolic Activity of Adipose Tissue in Nscl-2 Mutant Mice

BACKGROUND: In mammals the interplay between the peripheral nervous system (PNS) and adipose tissue is widely unexplored. We have employed mice, which develop an adult onset of obesity due to the lack the neuronal specific transcription factor Nscl-2 to investigate the interplay between the nervous system and white adipose tissue (WAT). METHODOLOGY: Changes in the architecture and innervation of WAT were compared between wildtype, Nscl2-/-, ob/ob and Nscl2-/-//ob/ob mice using morphological methods, immunohistochemistry and flow cytometry. Metabolic alterations in mutant mice and in isolated cells were investigated under basal and stimulated conditions. PRINCIPAL FINDINGS: We found that Nscl-2 mutant mice show a massive reduction of innervation of white epididymal and paired subcutaneous inguinal fat tissue including sensory and autonomic nerves as demonstrated by peripherin and neurofilament staining. Reduction of innervation went along with defects in the formation of the microvasculature, accumulation of cells of the macrophage/preadipocyte lineage, a bimodal distribution of the size of fat cells, and metabolic defects of isolated adipocytes. Despite a relative insulin resistance of white adipose tissue and isolated Nscl-2 mutant adipocytes the serum level of insulin in Nscl-2 mutant mice was only slightly increased. CONCLUSIONS: We conclude that the reduction of the innervation and vascularization of WAT in Nscl-2 mutant mice leads to the increase of preadipocyte/macrophage-like cells, a bimodal distribution of the size of adipocytes in WAT and an altered metabolic activity of adipocytes

Moonraker -- Enceladus Multiple Flyby Mission

Enceladus, an icy moon of Saturn, possesses an internal water ocean and jets expelling ocean material into space. Cassini investigations indicated that the subsurface ocean could be a habitable environment having a complex interaction with the rocky core. Further investigation of the composition of the plume formed by the jets is necessary to fully understand the ocean, its potential habitability, and what it tells us about Enceladus' origin. Moonraker has been proposed as an ESA M-class mission designed to orbit Saturn and perform multiple flybys of Enceladus, focusing on traversals of the plume. The proposed Moonraker mission consists of an ESA-provided platform, with strong heritage from JUICE and Mars Sample Return, and carrying a suite of instruments dedicated to plume and surface analysis. The nominal Moonraker mission has a duration of 13.5 years. It includes a 23-flyby segment with 189 days allocated for the science phase, and can be expanded with additional segments if resources allow. The mission concept consists in investigating: i) the habitability conditions of present-day Enceladus and its internal ocean, ii) the mechanisms at play for the communication between the internal ocean and the surface of the South Polar Terrain, and iii) the formation conditions of the moon. Moonraker, thanks to state-of-the-art instruments representing a significant improvement over Cassini's payload, would quantify the abundance of key species in the plume, isotopic ratios, and physical parameters of the plume and the surface. Such a mission would pave the way for a possible future landed mission.Comment: Accepted for publication in The Planetary Science Journa

Moonraker: Enceladus Multiple Flyby Mission

Enceladus, an icy moon of Saturn, possesses an internal water ocean and jets expelling ocean material into space. Cassini investigations indicated that the subsurface ocean could be a habitable environment having a complex interaction with the rocky core. Further investigation of the composition of the plume formed by the jets is necessary to fully understand the ocean, its potential habitability, and what it tells us about Enceladus’s origin. Moonraker has been proposed as an ESA M-class mission designed to orbit Saturn and perform multiple flybys of Enceladus, focusing on traversals of the plume. The proposed Moonraker mission consists of an ESA-provided platform with strong heritage from JUICE and Mars Sample Return and carrying a suite of instruments dedicated to plume and surface analysis. The nominal Moonraker mission has a duration of ∼13.5 yr. It includes a 23-flyby segment with 189 days allocated for the science phase and can be expanded with additional segments if resources allow. The mission concept consists of investigating (i) the habitability conditions of present-day Enceladus and its internal ocean, (ii) the mechanisms at play for the communication between the internal ocean and the surface of the South Polar Terrain, and (iii) the formation conditions of the moon. Moonraker, thanks to state-of-the-art instruments representing a significant improvement over Cassini's payload, would quantify the abundance of key species in the plume, isotopic ratios, and the physical parameters of the plume and the surface. Such a mission would pave the way for a possible future landed mission

Paediatric Home Artificial Nutrition in Italy: Report from 2016 Survey on Behalf of Artificial Nutrition Network of Italian Society for Gastroenterology, Hepatology and Nutrition (SIGENP)

Home Artificial Nutrition (HAN) is a safe and efficacious technique that insures children's reintegration into the family, society and school. Epidemiological data on paediatric HAN in Italy are not available. Aim: to detect the prevalence and incidence of Home Parenteral Nutrition (HPN) and Home Enteral Nutrition (HEN), either via tube or mouth, in Italy in 2016. Materials and methods: a specific form was sent to all registered SIGENP members and investigators of local HAN centres, inviting them to provide the requested centre's data and demographics, underlying diseases and HAN characteristics of the patients. Results: we recorded 3403 Italian patients on HAN aged 0 to 19 years from 22 centres: 2277 HEN, 950 Oral Nutritional Supplements (ONS) and 179 HPN programs. The prevalence of HEN (205 pts/million inhabitants) and HPN (16 pts/million inhabitants) has dramatically increased in Italy in the last 9 years. Neurodisabling conditions were the first indication for HEN by tube or mouth while HPN is mainly requested in digestive disorders. Conclusions: HAN is a widespread and rapidly growing treatment in Italy, as well as in other European countries. Awareness of its extent and characteristics helps improving HAN service and patients' quality of life

Simulation studies for the Mini-EUSO detector

Mini-EUSO is a mission of the JEM-EUSO program flying onboard the International Space Station since August 2019. Since the first data acquisition in October 2019, more than 35 sessions have been performed for a total of 52 hours of observations. The detector has been observing Earth at night-time in the UV range and detected a wide variety of transient sources all of which have been modeled through Monte Carlo simulations. Mini-EUSO is also capable of detecting meteors and potentially space debris and we performed simulations for such events to estimate their impact on future missions for cosmic ray science from space. We show here examples of the simulation work done in this framework to analyze the Mini-EUSO data. The expected response of Mini-EUSO with respect to ultra high energy cosmic ray showers has been studied. The efficiency curve of Mini-EUSO as a function of primary energy has been estimated and the energy threshold for Cosmic Rays has been placed to be above 10$^{21}$ eV. We compared the morphology of several transient events detected during the mission with cosmic ray simulations and excluded that they can be due to cosmic ray showers. To validate the energy threshold of the detector, a system of ground based flashers is being used for end-to-end calibration purposes. We therefore implemented a parameterization of such flashers into the JEM-EUSO simulation framework and studied the response of the detector with respect to such sources

Neutrino Target-of-Opportunity Observations with Space-based and Suborbital Optical Cherenkov Detectors

Cosmic-ray accelerators capable of reaching ultra-high energies are expected to also produce very-high energy neutrinos via hadronic interactions within the source or its surrounding environment. Many of the candidate astrophysical source classes are either transient in nature or exhibit flaring activity. Using the Earth as a neutrino converter, suborbital and space-based optical Cherenkov detectors, such as EUSO-SPB2 and POEMMA, will be able to detect upward-moving extensive air showers induced by decay tau-leptons generated from cosmic tau neutrinos with energies ∼10 PeV and above. Both EUSO-SPB2 and POEMMA will be able to quickly repoint, enabling rapid response to astrophysical transient events. we calculate the transient sensitivity and sky coverage for both EUSO-SPB2 and POEMMA, accounting for constraints imposed by the Sun and the Moon on the observation time. We also calculate both detectors\u27 neutrino horizons for a variety of modeled astrophysical neutrino fluences. We find that both EUSO-SPB2 and POEMMA will achieve transient sensitivities at the level of modeled neutrino fluences for nearby sources. We conclude with a discussion of the prospects of each mission detecting at least one transient event for various modeled astrophysical neutrino sources