Energy metabolism and the skeleton: Reciprocal interplay

The relation between bone remodelling and energy expenditure is an intriguing, and yet unexplained, challenge of the past ten years. In fact, it was only in the last few years that the skeleton was found to function, not only in its obvious roles of body support and protection, but also as an important part of the endocrine system. In particular, bone produces different hormones, like osteocalcin (OC), which influences energy expenditure in humans. The undercarboxylated form of OC has a reduced affinity for hydroxyapatite; hence it enters the systemic circulation more easily and exerts its metabolic functions for the proliferation of pancreatic β-cells, insulin secretion, sensitivity, and glucose tolerance. Leptin, a hormone synthesized by adipocytes, also has an effect on both bone remodelling and energy expenditure; in fact it inhibits appetite through hypothalamic influence and, in bone, stimulates osteoblastic differentiation and inhibits apoptosis. Leptin and serotonin exert opposite influences on bone mass accrual, but several features suggest that they might operate in the same pathway through a sympathetic tone. Serotonin, in fact, acts via two opposite pathways in controlling bone remodelling: central and peripheral. Serotonin product by the gastrointestinal tract (95%) augments bone formation by osteoblast, whereas brain-derived serotonin influences low bone mineral density and its decrease leads to an increase in bone resorption parameters. Finally, amylin (AMY) acts as a hormone that alters physiological responses related to feeding, and plays a role as a growth factor in bone. In vitro AMY stimulates the proliferation of osteoblasts, and osteoclast differentiation. Here we summarize the evidence that links energy expenditure and bone remodelling, with particular regard to humans

Enhancement of hydrogen production rate by high biomass concentrations of Thermotoga neapolitana

The objective of this study was to enhance the hydrogen production rate of dark fermentation in batch operation. For the first time, the hyperthermophilic pure culture of Thermotoga neapolitana cf. Capnolactica was applied at elevated biomass concentrations. The increase of the initial biomass concentration from 0.46 to 1.74 g cell dry weight/L led to a general acceleration of the fermentation process, reducing the fermentation time of 5 g glucose/L down to 3 h with a lag phase of 0.4 h. The volumetric hydrogen production rate increased from 323 (±11) to 654 (±30) mL/L/h with a concomitant enhancement of the biomass growth and glucose consumption rate. The hydrogen yield of 2.45 (±0.09) mol H2/mol glucose, the hydrogen concentration of 68% in the produced gas and the composition of the end products in the digestate, i.e. 62.3 (±2.5)% acetic acid, 23.5 (±2.9)% lactic acid and 2.3 (±0.1)% alanine, remained unaffected at increasing biomass concentrations

Non-arthritic Hip Score: translation, cultural adaptation and validation of the Italian version

BACKGROUNDː the aim of the study was to translate the Nonarthritic Hip Score (NAHS) questionnaire into the Italian language, to adapt it into the Italian culture and to validate it. METHODSː Translation and cultural adaptation were performed following international guidelines. To assess the reliability of the tool internal consistency and test-retest reliability were evaluated through Cronbach’s alpha and Intraclass Correlation Coefficient (ICC) respectively. Validity was evaluated by Pearson’s correlation coefficient between the NAHS, the Lequesne Index of Severity for Osteoarthritis of the Hip (LISOH) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC), that were administered together. These three questionnaires were applied to a population of 64 individuals between 19 and 82 years old with generic hip injures or diseases. RESULTSː The items of the original version of NAHS are similar or equal to the items of the Italian version of NAHS. Cronbach’s α was 0.614 (Pain); 0.821 (Symptom); 0.877 (Function); 0.896 (Activity). ICC for total score was 0.905. The correlation with the WOMAC was 0.850 (p< 0.01) and with the LISOH was 0.738 (p<0.01). CONCLUSIONSː The NAHS showed positive results for reliability and validity so it was translated into Italian language and was cross-culturally adapted to Italian culture. This questionnaire is a good instrument in clinical practice and scientific research for the evaluation of young and active individuals affected by hip injures or diseases

Sacrocolpopexy after sub-total hysterectomy vs. sacral hysteropexy for advanced urogenital prolapse: A propensity-matched study

ObjectiveTo compare objective and subjective outcomes of laparoscopic sacral colpopexy with supracervical hysterectomy (L-SCP) and robotic sacral hysteropexy (R-SHP). MethodsThis is a multicenter retrospective propensity score matched study. In the period between January 2014 and December 2018, we enrolled 161 patients with apical prolapse stage 2 or above, alone or with multicompartment descensus. ResultsAfter propensity-match analysis, there were 44 women for each group. Patients of the two groups had similar preoperative characteristics. No difference was found in terms of estimated blood loss, hospital stay, operative time, and intraoperative or postoperative complications. Subjective success rate, 12 months after surgery, was statistically better in the L-SCP group (P = 0.034): 81.8% and 97.8% women had Patient Global Impression of Improvement scores less than 3, in R-SHP and L-SCP, respectively. The objective cure rate was high in both groups without any significant differences in recurrence rate (P = 0.266). ConclusionBoth procedures are safe and effective in pelvic organ prolapse treatment. Patients who no longer desire uterine preservation could be encouraged to consider L-SCP. R-SHP is an alternative in women who are strongly motivated to preserve their uterus in the absence of abnormal uterine findings

Genetic deletion in uncoupling protein 3 augments 18F-fluorodeoxyglucose cardiac uptake in the ischemic heart

BACKGROUND: We investigated the effects of uncoupling protein 3 (UCP3) genetic deletion on 18F-fluorodeoxyglucose (FDG) cardiac uptake by positron emission tomography (PET)/computed tomography (CT) dedicated animal system after permanent coronary artery ligation. METHODS: Cardiac 18F-FDG PET/CT was performed in UCP3 knockout (UCP3-/-) and wild-type (WT) mice one week after induction of myocardial infarction or sham procedure. RESULTS: In sham-operated mice no difference in left ventricular (LV) volume was detectable between WT and UCP3-/-. After myocardial infarction, LV volume was higher in both WT and UCP3-/- compared to sham animals, with a significant interaction (p < 0.05) between genotype and myocardial infarction. In sham-operated animals no difference in FDG standardized uptake value (SUV) was detectable between WT (1.8 ± 0.6) and UCP3-/- (1.8 ± 0.6). After myocardial infarction SUV was significantly higher in remote areas than in infarcted territories in both UCP3-/- and WT mice (both p < 0.01). Moreover, in remote areas, SUV was significantly higher (p < 0.001) in UCP3-/- as compared to WT, while in the infarcted territory SUV was comparable (p = 0.29). A significant relationship (r = 0.68, p < 0.001) between LV volume and SUV was found. CONCLUSIONS: In a mice model of permanent coronary occlusion, UCP3 deficiency results in a metabolic shift that favored glycolytic metabolism and increased FDG uptake in remote areas

An orbit determination software suite for Space Surveillance and Tracking applications

The growth of both operational satellites and orbital debris is creating the requirement for more robust Space Surveillance and Tracking (SST)-related applications. These systems necessarily must leverage ground-based sensors (optical and radar) to realise higher performance solutions. In this context, the European Union Space Surveillance and Tracking (EUSST) consortium groups European national agencies and institutions, and is in charge of carrying out the following services: conjunction analysis, fragmentation analysis and re-entry prediction, and the Italian Air Force is in charge of the latter two. In this framework, the Italian SST Operational Centre (ISOC) has recently upgraded its system to the ISOC Suite, an integrated platform providing multiple functions and services in the SST domain. This paper presents the orbit determination functions provided by the novel ISOC Suite. First, a statistical index is computed to assess the measurements correlation to a catalogued object. If it is successful, the object predicted orbit is refined through measurements according either to batch or sequential filters; otherwise these are used to refine a first estimate of the target orbital state computed according to dedicated methodologies. After the presentation of the prototypal software architecture, the ISOC Suite performance are assessed and discussed both in terms of synthetic and real data

Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the european prospective investigation into nutrition and cancer (EPIC-Italy) cohort

The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset

A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events

Background. Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predict diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2. Results. Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent datasets from Europe and the US. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant). Conclusions. We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures

Epigenetic Signatures at AQP3 and SOCS3 Engage in Low-Grade Inflammation across Different Tissues

Background Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation. Results Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays. Four CpG sites (located at BCL3, AQP3, SOCS3, and cg19821297 intergenic at chromosome 19p13.2, P <= 1.01E-07) were significantly hypomethylated at high CRP concentrations independent of various confounders including age, sex, BMI, smoking, and white blood cell composition. Findings were not sex-specific. CRP-related top genes were enriched in JAK/STAT pathways (Benjamini-Hochberg corrected P < 0.05). Results were followed-up in three studies using DNA from peripheral blood (EPICOR, n = 503) and adipose tissue (TwinsUK, n = 368) measured as described above and from liver tissue (LMU liver cohort, n = 286) measured by MALDI-TOF mass spectrometry using EpiTYPER. CpG sites at the AQP3 locus (significant p-values in peripheral blood = 1.72E-03 and liver tissue = 1.51E-03) and the SOCS3 locus (p-values in liver < 2.82E-05) were associated with CRP in the validation panels. Conclusions Epigenetic modifications seem to engage in low-grade inflammation, possibly via JAK/STAT mediated pathways. Results suggest a shared relevance across different tissues at the AQP3 locus and highlight a role of DNA methylation for CRP regulation at the SOCS3 locus