MicroRNA-Mediated Metabolic Shaping of the Tumor Microenvironment

The metabolism of cancer cells is generally very different from what is found in normal counterparts. However, in a tumor mass, the continuous crosstalk and competition for nutrients and oxygen among different cells lead to metabolic alterations, not only in cancer cells, but also in the different stromal and immune cells of the tumor microenvironment (TME), which are highly relevant for tumor progression. MicroRNAs (miRs) are small non-coding RNAs that silence their mRNA targets post-transcriptionally and are involved in numerous physiological cell functions as well as in the adaptation to stress situations. Importantly, miRs can also be released via extracellular vesicles (EVs) and, consequently, take part in the bidirectional communication between tumor and surrounding cells under stress conditions. Certain miRs are abundantly expressed in stromal and immune cells where they can regulate various metabolic pathways by directly suppressing enzymes or transporters as well as by controlling important regulators (such as transcription factors) of metabolic processes. In this review, we discuss how miRs can induce metabolic reprogramming in stromal (fibroblasts and adipocytes) and immune (macrophages and T cells) cells and, in turn, how the biology of the different cells present in the TME is able to change. Finally, we debate the rebound of miR-dependent metabolic alterations on tumor progression and their implications for cancer management

Osteopontin plasma levels and accelerated atherosclerosis in patients with CAD undergoing PCI: a prospective clinical study.

OBJECTIVES: Growing evidence supports the role played by inflammation in atherosclerosis. Identifying sensitive biomarkers is useful in predicting accelerated atherosclerosis. We investigated prospectively the relationship between plasma levels of inflammatory biomarkers [osteopontin, C-reactive protein (CRP), interleukin-6 (IL-6)] and instent restenosis, and rapid coronary plaque progression in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: We studied 77 patients with CAD: 45 affected by unstable angina/non-ST elevation myocardial infarction [acute coronary syndrome (ACS)], and 32 by chronic coronary syndrome (CCS). Plasma osteopontin, IL-6, and CRP levels were measured before intervention in all patients; measurements were carried out on the basis of the following time course at 1,15, 30, 90, and 180 days follow-up in a subgroup of 39 consenting patients. Clinical and biohumoral data were correlated with baseline and 6-month PCI follow-up angiography. RESULTS: Osteopontin, IL-6, and CRP were higher in patients with ACS than in those with CCS (analysis of variance: P<0.001, 0.05, and 0.05, respectively). Baseline osteopontin levels proved to be associated with rapid coronary plaque progression (P=0.005) and instent restenosis (P=0.05). The highest osteopontin levels were found in patients with CAD with both rapid plaque progression and instent restenosis (P=0.003). PCI increased inflammatory markers acutely, and osteopontin remained elevated in patients with ACS. Patients with ACS showed a higher percentage (74%) of rapid plaque progression than those with CCS (26%) (P<0.05). CONCLUSION: The study prospectively shows the link between inflammatory status and accelerated atherosclerosis in patients with CAD undergoing PCI. The baseline and persistent rise of osteopontin is an expression of its contribution to the accelerated plaque progression, and therefore osteopontin may be a useful prognostic biomarker

Mapping Protein Structure Changes with Cysteine Labeling Kinetics by Mass Spectrometry

Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide "system" inertia-really difficult to be overcome-and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE) in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of "fertilizing a patient engagement ecosystem": an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient "disengagement" is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper

Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α–dependent microRNA (miR)–210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210–based therapeutic and diagnostic strategies

&quot;Delirium Day&quot;: A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

Bullying perpetration and victimization in early adolescence: physiological response to social exclusion

The present study investigated the associations between bullying perpetration and victimization and physiological reactivity to social exclusion. The participants were 28 early adolescents (17 boys and 11 girls; Mage= 11.55; SD = 1.34). Bullying perpetration and victimization were assessed by peer nominations. To elicit social exclusion, participants were first included and then excluded in a laboratory paradigm (Cyberball). Physiological reactivity (i.e., nose tip temperature) was detected through thermal infrared imaging during the computer simulation. Nose temperature variations during inclusion and exclusion were compared between each other. Results showed increasing skin temperature during exclusion, compared to inclusion, for the whole sample, indicating that being excluded affected physiological reactivity. However, victimization was associated with higher skin temperature during exclusion, compared to bullying. The present findings suggest the importance of combining behavioral and contact-free physiological measures when studying bullying perpetration and victimization by peers