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Cristina Piras,1 Bruno Maria Pintus,2 Antonio Noto,1 Maurizio Evangelista,3 Vassilios Fanos,4 Mario Musu,2 Michele Mussap,4 Luigi Atzori,1 Salvatore Sardo,2 Gabriele Finco2 1Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042, Italy; 2Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, 09042, Italy; 3Department of Anesthesiology and Pain Medicine, Cattolica University, Rome, 00168, Italy; 4Department of Surgical Science, University of Cagliari, Monserrato, 09042, ItalyCorrespondence: Antonio Noto, Email antonionoto@hotmail.comAbstract: Chronic pain affects almost 20% of the European adult population and it significantly reduces patients’ quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.Keywords: pain, chronic pain, metabolomics, microbiomics, biomarkers

The actual reference range of serum uric acid has been assessed according to its variations among healthy individuals. i.e. those without clinical evidence of gout. By this approach, serum uric acid values between 3.5 and 7.2 mg/dL in adult males and postmenopausal women and between 2.6 and 6.0 mg/dL in premenopausal women have been identified as normal in many countries. However, this definition of normal range of serum uric acid in the general population is inevitably influenced by what we consider as "normal", since the absence of gout flares does not necessarily imply the absence of uric acid-related damage. Indeed, a growing body of evidence indicates that silent deposition of monosodium urate crystals as a result of hyperuricaemia may occur and lead to early destructive skeletal changes. In addition, a growing body of evidences demonstrates that uric acid might play a pathophysiological role in many "cardio-nephro-metabolic" disorders, which seems to be independent of the deposition of monosodium urate crystals, since it is evident also for serum uric acid concentrations below the saturation point for monosodium urate. Taken together, these findings strongly suggest to carefully reconsider the concept of "asymptomaticity" for chronic hyperuricemia and to consequently revise the normal range of serum uric acid levels also considering the progressive worldwide increase of circulating levels of uric acid, which could lead to a "shift to right" (i.e. toward higher values) of normal range. In the light of the new scientific knowledge on the pathophysiological role of uric acid in human disease, a threshold value < 6.0 mg/dL (< 360 μmol/L) seems to better identify true "healthy subjects" and should reasonably be considered for all subjects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Candida bloodstream infections (BSI) represent an important problem in Intensive Care Units (ICUs). The epidemiology of candidemia is changing with an increase in the proportion of Candida (C.) non-albicans. OBJECTIVES: An Italian 2-year observational survey on ICU was conducted to evaluate the species distribution and possible differences between BSI caused by C. albicans and C. non-albicans. For comparative purposes, we performed a European literature-based review to evaluate distribution and frequency of Candida spp. causing ICU candidemia, during the period 2000-2013. MATERIALS AND METHODS: This laboratorybased survey involved 15 microbiology centers (GISIA-3 study). All candidemia episodes in adult patients were considered. Data were prospectively collected from 2007 to 2008. PubMed was searched for peer-reviewed articles. RESULTS: In total, 462 candidemia episodes were collected. C. albicans accounted for 49.4% of the isolates, followed by C. parapsilosis (26.2%) and C. glabrata (10.4%). Mortality was higher in patients with C. non-albicans than C. albicans (47.3% vs. 32.4 %, p > 0.05). Among risk factors, parenteral nutrition was more common (p = 0.02) in non-albicans candidemia, while surgery was more frequent (p = 0.02) in C. albicans candidemia. Twenty-four relevant articles were identified. C. albicans was the predominant species in almost all studies (range 37.9% -76.3%). C. glabrata was commonly isolated in the German-speaking countries, France, UK and North Europe; C. parapsilosis in Turkey, Greece and Spain. CONCLUSIONS: Although C. non-albicans BSI is increasing, our study shows that C. albicans is still the predominant species in ICU candidemia. There are differences in the epidemiology of Candida BSI among European countries, with a prevalence of C. glabrata and C. parapsilosis in Northern and Southern countries, respectively. [ABSTRACT FROM AUTHOR]

Procalcitonin (PCT) has been proposed as an interesting marker in the diagnosis, prognosis, and response to treatment of patient with neonatal sepsis. Fifty-nine neonates (34 males and 25 females) with a mean gestational age of approximately 31 weeks and a mean weight of about 1750 g admitted in the Neonatal Intensive Care Unit of Cagliari (Italy) were evaluated in controls and in infected neonates, before and after 48 h of life. From our experience it emerges that PCT is a marker of early and late neonatal sepsis which is reliable in preterm neonates. A cut-off of 0.5 ng/ml starting from the third day of life appears to be capable of ensuring good test sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated the important role of growth factors, particularly epidermal growth factor (EGF) and transforming growth factor α (TGFα), in cellular growth after renal damage. EGF is mainly synthesized by the kidney. Many studies indicate that urinary EGF concentration significantly decreases in patients with acute and chronic renal failure. In this study we determined urinary EGF concentrations in children with renal and/or urological pathologies. We investigated 38 patients, 17 males and 21 females, of 3.34 ± 2.96 years (mean ± standard deviation), who were followed in the Nephrologic Unit of the Pediatric Department of the University of Verona for recurrent urinary tract infections: seven of these had vesicoureteric reflux and 4 had hypodysplasia. The results were compared with those from a healthy age-matched group of 44 children. In all patients, we assessed renal function including an examination of the urine with a microbiological evaluation. Moreover, a renal ultrasound and a voiding cystourethrogram were performed. Urinary EGF was measured by a radioimmunoassay, using polyclonal goat antibodies. In all patients, laboratory parameters were within the normal range. In 34 patients the renal ultrasound was negative and in 4 cases structural alterations of the renal parenchyma were found. Voiding cystourethrography detected 7 instances of vesicoureteric reflux. In controls 10°, 50°, 90° percentile uEGF values were 7.3, 19 and 40.4μg/L, respectively. Mean urinary EGF values were 22.22 ± 16 μg/L. Urinary EGF values were 54 ± 35.2 μg/L in patients with recurrent urinary tract infections and without urinary malformations, 81 ± 29.37 μg/L in patients with vesicoureteric reflux and 22.30 ± 22.90μg/L in patients with hypodysplasia, respectively. There was a statistical significant difference between controls and groups A (p < 0.001) and B (p < 0.001) respectively,... [ABSTRACT FROM AUTHOR]

In this study, we examine C-reactive protein (CRP) and serum amyloid protein A (SAA). Although the former is the best known and most commonly used indicator of inflammation, certain considerations underline the inadequacy of CRP determination alone for the early diagnosis of infection. In fact symptoms often precede the CRP elevation. SAA protein comprises a family of polymorphic apolipoproteins produced mainly by the liver. and several studies have stressed its importance in the diagnosis and monitoring of various diseases. Pathological SAA values are often detected in association with normal CRP concentrations. SAA rises earlier and more sharply than CRP. Finally, contrary to CRP, SAA presents the same trend in viral as well as bacterial infections. Although the data available on SAA in neonates are currently very limited, it is possible to postulate a role of primary importance for SAA in the management of neonatal infections. [ABSTRACT FROM AUTHOR]

Purpose To investigate the radiosensitizing capacity and therapeutic efficacy of the ataxia-telangiectasia mutated (ATM) inhibitor KU60019 on orthotopic glioblastoma (GB) driven by primary glioma initiating cells (GIC) with various p53 statuses. Methods Orthotopic GB have been developed in mice by intracranial injection of different GIC lines. Following tumor development, KU60019 was delivered to the site of the tumor [1]. The irradiation of orthotopic GB was performed by an RS 2000 Biological Irradiator (Rad Source Technologies) whose delivered dose was verified by a RadCal Accu-Gold system (Monrovia) equipped with a 10X6-0.6 High Dose Rate Chamber. The dose was confirmed by radiochromic films (Gafchromic® EBT3) placed over and under the mouse head. The prescription dose ranged 0.5–2.5 Gy. MRI of the orthotopic tumors was performed by a clinical 3T scanner (Signa EXCITE®HDxT, GE, Milwaukee, USA) with mice positioned in a prototype coil (linear birdcage transmit/receive coil, Flick Engineering Solutions BV-General Electric). Tumor volumes were determined by a software for quantitative MRI (GRES) [2]. Results A limited, but significant, elongation of median animal survival was observed after one radiosensitization cycle performed with one KU60019 CED administration followed by three ionizing radiation (IR) fractions as compared to animals treated with vehicle + IR [101 vs 91 days – Hazard Ratio: 4.922]. Other irradiation schedules failed to improve survival of animals bearing orthotopic GBs. Conclusions Further research to determine general and effective conditions for radiosensitization of orthotopic GBs by ATM inhibitors is warranted. [ABSTRACT FROM AUTHOR]