The Effects of Prebiotic Supplementation with OMNi-LOGiC® FIBRE on Fecal Microbiome, Fecal Volatile Organic Compounds, and Gut Permeability in Murine Neuroblastoma-Induced Tumor-Associated Cachexia

Malignant diseases can cause tumor-associated cachexia (TAC). Supplementation with prebiotic non-digestible carbohydrates exerts positive metabolic effects in experimental oncologic diseases. The aim of this project was to assess the effect of prebiotic supplementation with OMNi-LOGiC® FIBRE on intestinal microbiome, bacterial metabolism, gut permeability, and inflammation in a murine model of neuroblastoma (NB)-associated TAC. For this study, 2,000,000 NB cells (MHH-NB11) were implanted into athymic mice followed by daily supplementation with water or 200 mg prebiotic oligosaccharide (POS) OMNi-LOGiC® FIBRE (NB-Aqua, n = 12; NB-POS, n = 12). Three animals of each tumor group did not develop NB. The median time of tumor growth (first visibility to euthanasia) was 37 days (IQR 12.5 days) in the NB-Aqua group and 37 days (IQR 36.5 days) in the NB-POS group (p = 0.791). At euthanasia, fecal microbiome and volatile organic compounds (VOCs), gut permeability (fluorescein isothiocyanate-dextran (FITC-dextran), and gut barrier markers were measured. Values were compared to sham animals following injection of culture medium and gavage of either water or OMNi-LOGiC® FIBRE (SH-Aqua, n = 10; SH-POS, n = 10). Alpha diversity did not differ significantly between the groups. Principal coordinate analysis (PCoA) revealed clustering differences between Aqua and POS animals. Both NB and POS supplementation led to taxonomic alterations of the fecal microbiome. Of 49 VOCs, 22 showed significant differences between the groups. NB animals had significantly higher gut permeability than Aqua animals; POS did not ameliorate these changes. The pore and leak pathways of tight junctions did not differ between groups. In conclusion, our results suggest that NB-induced TAC causes increased gut permeability coupled with compositional changes in the fecal microbiome and VOC profile. Prebiotic supplementation with OMNi-LOGiC® FIBRE seemed to induce modifications of the fecal microbiome and VOC profile but did not improve gut permeability

Prevention of healthcare associated infections: Medical and nursing students' knowledge in Italy.

BACKGROUND: The training of health workers is a key issue for the prevention of healthcare associated infections. OBJECTIVES: To evaluate knowledge of nursing and medical students concerning the prevention of healthcare associated infections. DESIGN: A cross-sectional study. SETTING: University hospitals in nine Italian cities. PARTICIPANTS: One thousand four hundred sixty one healthcare students (607 medical students and 854 nursing students). METHODS: The study was performed using a questionnaire investigating 3 areas, each having different possible points: standard precautions=12; hand hygiene=8; healthcare associated infections=5, for an overall perfect score of 25. Scores that met a cutoff ≥17.5 were considered to be indicative of an acceptable level of knowledge. Factors associated with an acceptable level of knowledge were analyzed using a logistic regression model. RESULTS: Mean overall score (±SD) was 18.1±3.2. Nursing students (18.6±2.9) obtained a higher overall score than medical students (17.4±3.5) (p<0.001). Weighed scores (±SD) by area were: 10.3 (±2.0) for standard precautions, 5.0 (±1.3) for hand hygiene and 2.8 (±1.1) for healthcare associated infections. Knowledge level concerning the three areas was different between medical and nursing students (p<0.001). The probability of finding acceptable knowledge was smaller for medical students (OR: 0.54 p<0.0001) and for students aged ≥24years (OR: 0.39 p<0.0001). CONCLUSION: The overall score showed an acceptable level of knowledge for the whole sample; but, considering separately the two curricula, only nursing students reached the minimum acceptable score. It seems important to investigate what is working better in nursing than in medical education in order to implement and validate new teaching approaches

Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 3. Synthesis, Structure-Affinity Relationships, and Pharmacological Characterization of 6-Substituted 4-Quinolone-3-carboxamides as Highly Selective Cannabinoid-2 Receptor Ligands

A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting Ki >100 nM, all the quinolone-3- carboxamides 2 proved to be high affinity CB2 ligands, with Ki values ranging from 73.2 to 0.7 nM and selectivity [SI=Ki(CB1)/Ki(CB2)] varying from >14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI<1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonistlike behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors

Close Relationship Between Media to Lumen Ratio of Subcutaneous Small Arteries and Wall to Lumen Ratio of Retinal Arterioles Evaluated Non Invasively By Scanning Laser Doppler Flowmetry

Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media to lumen (M/L) ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alteration observed. In addition, M/L of small arteries evaluated by micromyography has a strong prognostic significance; however its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Non-invasive measurement of wall to lumen (W/L) of retinal arterioles using scanning laser doppler flowmetry (SLDF) has been recently introduced (Harazny J et al, Hypertension 2007; 50:623-629). However, this new technique was never compared with micromyographic measurement, considered the gold standard approach. Methods and Results: We have investigated 37 subjects and patients. Twenty-three of them were hypertensives and 14 normotensives. Blood pressure values were 139/8817/10 mmHg and 125/7117/12 mm Hg, respectively (p<0.05). All patients underwent a biopsy of subcutaneous fat during an elective surgical intervention. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and M/L was measured. In addition, an evaluation of W/L of retinal arterioles by SLDF was performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). A close correlation was observed between M/L of subcutaneous small arteries and WL of retinal arterioles: rZ0.77, p<0.001 (see Figure). Conclusion: A non invasive and easily repeatable procedure (intraobserver and interobserver variation coefficient around 10%) such as an evaluation of the arterioles in the fundus oculi by SDLF may provide similar information regarding microvascular morphology compared in respect with an invasive, accurate and prognostically relevant micromyographic measurement of M/L