Previous Exposure to Cigarette Smoke Aggravates Experimental Cyclosporine-Induced Nephrotoxicity

Background/Aims: The effects of cigarette smoke (CS) on cyclosporine (CsA)-induced nephrotoxicity are poorly studied. This study aims to assess the effects of previous exposure to CS on CsA nephrotoxicity. Methods: Rats were either exposed to CS or sham (S) procedures for 10 min twice a day for 20 weeks. From the 16th to the 20th week, they received a low-salt diet. Beginning with the 17th week, they were given 2.5 mg/day CsA or vehicle (VH) for 3 weeks. The final groups were VH/CS, CsA/CS, VH/S, and CsA/S. On day 141, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), tubulointerstitial fibrosis, and CsA blood levels were measured and immunohistochemistry was analyzed for renal alpha-smooth muscle actin (SMA), nitrotyrosine, and vimentin. Results: CsA decrease in GFR was enhanced by CS exposure. CsA associated with CS induced higher periglomerular alpha-SMA and renal nitrotyrosine expression. CsA decreased RBF, but increased RVR, tubulointerstitial fibrosis, and alpha-SMA and renal vimentin expression. These changes and the CsA blood levels were not affected by CS exposure. Conclusion: CS aggravated the CsA-induced impairment of GFR and CS associated with CsA caused the development of periglomerular structural lesions and oxidative stress in a rat model of CsA nephrotoxicity. Copyright (C) 2012 S. Karger AG, Basel

Long-Term Occupational Exposure to Organic Solvents Affects Color Vision, Contrast Sensitivity and Visual Fields

The purpose of this study was to evaluate the visual outcome of chronic occupational exposure to a mixture of organic solvents by measuring color discrimination, achromatic contrast sensitivity and visual fields in a group of gas station workers. We tested 25 workers (20 males) and 25 controls with no history of chronic exposure to solvents (10 males). All participants had normal ophthalmologic exams. Subjects had worked in gas stations on an average of 9.6 +/- 6.2 years. Color vision was evaluated with the Lanthony D15d and Cambridge Colour Test (CCT). Visual field assessment consisted of white-on-white 24-2 automatic perimetry (Humphrey II-750i). Contrast sensitivity was measured for sinusoidal gratings of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0 and 20.0 cycles per degree (cpd). Results from both groups were compared using the Mann-Whitney U test. The number of errors in the D15d was higher for workers relative to controls (p<0.01). Their CCT color discrimination thresholds were elevated compared to the control group along the protan, deutan and tritan confusion axes (p<0.01), and their ellipse area and ellipticity were higher (p<0.01). Genetic analysis of subjects with very elevated color discrimination thresholds excluded congenital causes for the visual losses. Automated perimetry thresholds showed elevation in the 9 degrees, 15 degrees and 21 degrees of eccentricity (p<0.01) and in MD and PSD indexes (p<0.01). Contrast sensitivity losses were found for all spatial frequencies measured (p<0.01) except for 0.5 cpd. Significant correlation was found between previous working years and deutan axis thresholds (rho = 0.59; p<0.05), indexes of the Lanthony D15d (rho = 0.52; p<0.05), perimetry results in the fovea (rho = -0.51; p<0.05) and at 3, 9 and 15 degrees of eccentricity (rho = -0.46; p<0.05). Extensive and diffuse visual changes were found, suggesting that specific occupational limits should be created.

Fragmentation of extracellular DNA by long-term exposure to radiation from uranium in aquatic environments

Persistent harmful scenarios associated with disposal of radioactive waste, high-background radiation areas and severe nuclear accidents are of great concern regarding consequences to both human health and the environment. Of particular concern is the extracellular DNA in aquatic environments contaminated by radiological substances. Strand breaks induced by radiation promote decrease in the transformation efficiency for extracellular DNA. The focus of this study is the quantification of DNA damage following long-term exposure (over one year) to low doses of natural uranium (an alpha particle emitter) to simulate natural conditions, since nothing is known about alpha radiation induced damage to extracellular DNA. A high-resolution Atomic Force Microscope was used to evaluate DNA fragments. Double-stranded plasmid pBS as a model for extracellular DNA was exposed to different amounts of natural uranium. It was demonstrated that low concentrations of U in water (50 to 150 ppm) produce appreciable numbers of double strand breaks, scaling with the square of the average doses. The importance of these findings for environment monitoring of radiological pollution is addressed.

Oral exposure to methylmercury modifies the prostatic microenvironment in adult rats

Methylmercury (MeHg) is an environmental pollutant that is highly toxic to the central nervous system. As its effects on male reproductive system are poorly understood, this study was carried out to analyse the effects of MeHg on the rat prostate. To evaluate the MeHg toxicity on ventral prostate, three groups of adult male Wistar rats received oral doses of 0.5, 1.0 and 3.0mg/kg MeHg, respectively, on a daily basis for 14days. A fourth group was used as a control. The prostate weight was decreased in rats treated orally with 0.5mg/kg MeHg compared to controls. Also, Hg concentration increased significantly in the prostate after treatments. There were reductions in serum testosterone levels and androgen receptor immunoreactivity in animals receiving 3.0mgMeHg/kg. The stereological data showed changes in the prostatic epithelial, stromal and luminal compartments which varied according to the different doses. Histopathological alterations, such as chronic inflammation, stratified epithelial hyperplasia and epithelial inflammatory reactive atypia, were observed in the 0.5mg/kg MeHg-treated group. Epithelial atrophy was observed in the 3.0mg/kg MeHg-treated group. In conclusion, the MeHg affects prostatic homoeostasis resulting in histopathological changes that may be relevant in the pathogenesis of prostatic disease.

Aerobic exercise attenuates pulmonary injury induced by exposure to cigarette smoke

It has recently been suggested that regular exercise reduces lung function decline and risk of chronic obstructive pulmonary disease (COPD) among active smokers; however, the mechanisms involved in this effect remain poorly understood. The present study evaluated the effects of regular exercise training in an experimental mouse model of chronic cigarette smoke exposure. Male C57BL/6 mice were divided into four groups (control, exercise, smoke and smoke+exercise). For 24 weeks, we measured respiratory mechanics, mean linear intercept, inflammatory cells and reactive oxygen species (ROS) in bronchoalveolar lavage (BAL) fluid, collagen deposition in alveolar walls, and the expression of antioxidant enzymes, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase (TIMP) 1, interleukin (IL)-10 and 8-isoprostane in alveolar walls. Exercise attenuated the decrease in pulmonary elastance (p<0.01) and the increase in mean linear intercept (p=0.003) induced by cigarette smoke exposure. Exercise substantially inhibited the increase in ROS in BAL fluid and 8-isoprostane expression in lung tissue induced by cigarette smoke. In addition, exercise significantly inhibited the decreases in IL-10, TIMP1 and CuZn superoxide dismutase induced by exposure to cigarette smoke. Exercise also increased the number of cells expressing glutathione peroxidase. Our results suggest that regular aerobic physical training of moderate intensity attenuates the development of pulmonary disease induced by cigarette smoke exposure.

Immunomodulation of human monocytes following exposure to Lutzomyia intermedia saliva

Abstract Background Sand fly saliva contains potent and complex pharmacologic molecules that are able to modulate the host's hemostatic, inflammatory, and immune systems. In this study, we evaluated the effects of salivary gland sonicate (SGS) of Lutzomyia intermedia, the natural vector of Leishmania braziliensis, on monocytes obtained from the peripheral blood mononuclear cells (PBMC) of healthy volunteers. We investigated the effects of sand fly saliva on cytokine production and surface molecule expression of LPS-stimulated human monocytes uninfected or infected with L. braziliensis. Results Pre-treatment of non-infected human monocytes with L. intermedia SGS followed by LPS-stimulation led to a significant decrease in IL-10 production accompanied by a significant increase in CD86, CD80, and HLA-DR expression. Pre-treatment with SGS followed by LPS stimulation and L. braziliensis infection led to a significant increase in TNF-α, IL-6, and IL-8 production without significant alterations in co-stimulatory molecule expression. However, pre-treatment with L. intermedia SGS did not result in significant changes in the infection rate of human monocytes. Conclusion Our data indicate that L. intermedia saliva is able to modulate monocyte response, and, although this modulation is dissociated from enhanced infection with L. braziliensis, it may be associated with successful parasitism.

Previous exposure to musical auditory stimulation immediately influences the cardiac autonomic responses to the postural change maneuver in women

Background Chronic exposure to musical auditory stimulation has been reported to improve cardiac autonomic regulation. However, it is not clear if music acutely influences it in response to autonomic tests. We evaluated the acute effects of music on heart rate variability (HRV) responses to the postural change maneuver (PCM) in women. Method We evaluated 12 healthy women between 18 and 28 years old and HRV was analyzed in the time (SDNN, RMSSD, NN50 and pNN50) and frequency (LF, HF and LF/HF ratio) domains. In the control protocol, the women remained at seated rest for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. In the music protocol, the women remained at seated rest for 10 minutes, were exposed to music for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. HRV was recorded at the following time: rest, music (music protocol) 0–5, 5–10 and 10–15 min during standing. Results In the control protocol the SDNN, RMSSD and pNN50 indexes were reduced at 10–15 minutes after the volunteers stood up, while the LF (nu) index was increased at the same moment compared to seated rest. In the protocol with music, the indexes were not different from control but the RMSSD, pNN50 and LF (nu) were different from the music period. Conclusion Musical auditory stimulation attenuates the cardiac autonomic responses to the PCM.

Impatto di rifaximina sul microbiota intestinale: selezione di bifidobatteri antibiotico resistenti

The ideal approach for the long term treatment of intestinal disorders, such as inflammatory bowel disease (IBD), is represented by a safe and well tolerated therapy able to reduce mucosal inflammation and maintain homeostasis of the intestinal microbiota. A combined therapy with antimicrobial agents, to reduce antigenic load, and immunomodulators, to ameliorate the dysregulated responses, followed by probiotic supplementation has been proposed. Because of the complementary mechanisms of action of antibiotics and probiotics, a combined therapeutic approach would give advantages in terms of enlargement of the antimicrobial spectrum, due to the barrier effect of probiotic bacteria, and limitation of some side effects of traditional chemiotherapy (i.e. indiscriminate decrease of aggressive and protective intestinal bacteria, altered absorption of nutrient elements, allergic and inflammatory reactions). Rifaximin (4-deoxy-4’-methylpyrido[1’,2’-1,2]imidazo[5,4-c]rifamycin SV) is a product of synthesis experiments designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a non systemic antibiotic with a broad spectrum of antibacterial action, covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually non absorbed, its bioavailability within the gastrointestinal tract is rather high with intraluminal and faecal drug concentrations that largely exceed the MIC values observed in vitro against a wide range of pathogenic microorganisms. The gastrointestinal tract represents therefore the primary therapeutic target and gastrointestinal infections the main indication. The little value of rifaximin outside the enteric area minimizes both antimicrobial resistance and systemic adverse events. Fermented dairy products enriched with probiotic bacteria have developed into one of the most successful categories of functional foods. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” (FAO/WHO, 2002), and mainly include Lactobacillus and Bifidobacterium species. Probiotic bacteria exert a direct effect on the intestinal microbiota of the host and contribute to organoleptic, rheological and nutritional properties of food. Administration of pharmaceutical probiotic formula has been associated with therapeutic effects in treatment of diarrhoea, constipation, flatulence, enteropathogens colonization, gastroenteritis, hypercholesterolemia, IBD, such as ulcerative colitis (UC), Crohn’s disease, pouchitis and irritable bowel syndrome. Prerequisites for probiotics are to be effective and safe. The characteristics of an effective probiotic for gastrointestinal tract disorders are tolerance to upper gastrointestinal environment (resistance to digestion by enteric or pancreatic enzymes, gastric acid and bile), adhesion on intestinal surface to lengthen the retention time, ability to prevent the adherence, establishment and/or replication of pathogens, production of antimicrobial substances, degradation of toxic catabolites by bacterial detoxifying enzymatic activities, and modulation of the host immune responses. This study was carried out using a validated three-stage fermentative continuous system and it is aimed to investigate the effect of rifaximin on the colonic microbial flora of a healthy individual, in terms of bacterial composition and production of fermentative metabolic end products. Moreover, this is the first study that investigates in vitro the impact of the simultaneous administration of the antibiotic rifaximin and the probiotic B. lactis BI07 on the intestinal microbiota. Bacterial groups of interest were evaluated using culture-based methods and molecular culture-independent techniques (FISH, PCR-DGGE). Metabolic outputs in terms of SCFA profiles were determined by HPLC analysis. Collected data demonstrated that rifaximin as well as antibiotic and probiotic treatment did not change drastically the intestinal microflora, whereas bacteria belonging to Bifidobacterium and Lactobacillus significantly increase over the course of the treatment, suggesting a spontaneous upsurge of rifaximin resistance. These results are in agreement with a previous study, in which it has been demonstrated that rifaximin administration in patients with UC, affects the host with minor variations of the intestinal microflora, and that the microbiota is restored over a wash-out period. In particular, several Bifidobacterium rifaximin resistant mutants could be isolated during the antibiotic treatment, but they disappeared after the antibiotic suspension. Furthermore, bacteria belonging to Atopobium spp. and E. rectale/Clostridium cluster XIVa increased significantly after rifaximin and probiotic treatment. Atopobium genus and E. rectale/Clostridium cluster XIVa are saccharolytic, butyrate-producing bacteria, and for these characteristics they are widely considered health-promoting microorganisms. The absence of major variations in the intestinal microflora of a healthy individual and the significant increase in probiotic and health-promoting bacteria concentrations support the rationale of the administration of rifaximin as efficacious and non-dysbiosis promoting therapy and suggest the efficacy of an antibiotic/probiotic combined treatment in several gut pathologies, such as IBD. To assess the use of an antibiotic/probiotic combination for clinical management of intestinal disorders, genetic, proteomic and physiologic approaches were employed to elucidate molecular mechanisms determining rifaximin resistance in Bifidobacterium, and the expected interactions occurring in the gut between these bacteria and the drug. The ability of an antimicrobial agent to select resistance is a relevant factor that affects its usefulness and may diminish its useful life. Rifaximin resistance phenotype was easily acquired by all bifidobacteria analyzed [type strains of the most representative intestinal bifidobacterial species (B. infantis, B. breve, B. longum, B. adolescentis and B. bifidum) and three bifidobacteria included in a pharmaceutical probiotic preparation (B. lactis BI07, B. breve BBSF and B. longum BL04)] and persisted for more than 400 bacterial generations in the absence of selective pressure. Exclusion of any reversion phenomenon suggested two hypotheses: (i) stable and immobile genetic elements encode resistance; (ii) the drug moiety does not act as an inducer of the resistance phenotype, but enables selection of resistant mutants. Since point mutations in rpoB have been indicated as representing the principal factor determining rifampicin resistance in E. coli and M. tuberculosis, whether a similar mechanism also occurs in Bifidobacterium was verified. The analysis of a 129 bp rpoB core region of several wild-type and resistant bifidobacteria revealed five different types of miss-sense mutations in codons 513, 516, 522 and 529. Position 529 was a novel mutation site, not previously described, and position 522 appeared interesting for both the double point substitutions and the heterogeneous profile of nucleotide changes. The sequence heterogeneity of codon 522 in Bifidobacterium leads to hypothesize an indirect role of its encoded amino acid in the binding with the rifaximin moiety. These results demonstrated the chromosomal nature of rifaximin resistance in Bifidobacterium, minimizing risk factors for horizontal transmission of resistance elements between intestinal microbial species. Further proteomic and physiologic investigations were carried out using B. lactis BI07, component of a pharmaceutical probiotic preparation, as a model strain. The choice of this strain was determined based on the following elements: (i) B. lactis BI07 is able to survive and persist in the gut; (ii) a proteomic overview of this strain has been recently reported. The involvement of metabolic changes associated with rifaximin resistance was investigated by proteomic analysis performed with two-dimensional electrophoresis and mass spectrometry. Comparative proteomic mapping of BI07-wt and BI07-res revealed that most differences in protein expression patterns were genetically encoded rather than induced by antibiotic exposure. In particular, rifaximin resistance phenotype was characterized by increased expression levels of stress proteins. Overexpression of stress proteins was expected, as they represent a common non specific response by bacteria when stimulated by different shock conditions, including exposure to toxic agents like heavy metals, oxidants, acids, bile salts and antibiotics. Also, positive transcription regulators were found to be overexpressed in BI07-res, suggesting that bacteria could activate compensatory mechanisms to assist the transcription process in the presence of RNA polymerase inhibitors. Other differences in expression profiles were related to proteins involved in central metabolism; these modifications suggest metabolic disadvantages of resistant mutants in comparison with sensitive bifidobacteria in the gut environment, without selective pressure, explaining their disappearance from faeces of patients with UC after interruption of antibiotic treatment. The differences observed between BI07-wt e BI07-res proteomic patterns, as well as the high frequency of silent mutations reported for resistant mutants of Bifidobacterium could be the consequences of an increased mutation rate, mechanism which may lead to persistence of resistant bacteria in the population. However, the in vivo disappearance of resistant mutants in absence of selective pressure, allows excluding the upsurge of compensatory mutations without loss of resistance. Furthermore, the proteomic characterization of the resistant phenotype suggests that rifaximin resistance is associated with a reduced bacterial fitness in B. lactis BI07-res, supporting the hypothesis of a biological cost of antibiotic resistance in Bifidobacterium. The hypothesis of rifaximin inactivation by bacterial enzymatic activities was verified by using liquid chromatography coupled with tandem mass spectrometry. Neither chemical modifications nor degradation derivatives of the rifaximin moiety were detected. The exclusion of a biodegradation pattern for the drug was further supported by the quantitative recovery in BI07-res culture fractions of the total rifaximin amount (100 μg/ml) added to the culture medium. To confirm the main role of the mutation on the β chain of RNA polymerase in rifaximin resistance acquisition, transcription activity of crude enzymatic extracts of BI07-res cells was evaluated. Although the inhibition effects of rifaximin on in vitro transcription were definitely higher for BI07-wt than for BI07-res, a partial resistance of the mutated RNA polymerase at rifaximin concentrations > 10 μg/ml was supposed, on the basis of the calculated differences in inhibition percentages between BI07-wt and BI07-res. By considering the resistance of entire BI07-res cells to rifaximin concentrations > 100 μg/ml, supplementary resistance mechanisms may take place in vivo. A barrier for the rifaximin uptake in BI07-res cells was suggested in this study, on the basis of the major portion of the antibiotic found to be bound to the cellular pellet respect to the portion recovered in the cellular lysate. Related to this finding, a resistance mechanism involving changes of membrane permeability was supposed. A previous study supports this hypothesis, demonstrating the involvement of surface properties and permeability in natural resistance to rifampicin in mycobacteria, isolated from cases of human infection, which possessed a rifampicin-susceptible RNA polymerase. To understand the mechanism of membrane barrier, variations in percentage of saturated and unsaturated FAs and their methylation products in BI07-wt and BI07-res membranes were investigated. While saturated FAs confer rigidity to membrane and resistance to stress agents, such as antibiotics, a high level of lipid unsaturation is associated with high fluidity and susceptibility to stresses. Thus, the higher percentage of saturated FAs during the stationary phase of BI07-res could represent a defence mechanism of mutant cells to prevent the antibiotic uptake. Furthermore, the increase of CFAs such as dihydrosterculic acid during the stationary phase of BI07-res suggests that this CFA could be more suitable than its isomer lactobacillic acid to interact with and prevent the penetration of exogenous molecules including rifaximin. Finally, the impact of rifaximin on immune regulatory functions of the gut was evaluated. It has been suggested a potential anti-inflammatory effect of rifaximin, with reduced secretion of IFN-γ in a rodent model of colitis. Analogously, it has been reported a significant decrease in IL-8, MCP-1, MCP-3 e IL-10 levels in patients affected by pouchitis, treated with a combined therapy of rifaximin and ciprofloxacin. Since rifaximin enables in vivo and in vitro selection of Bifidobacterium resistant mutants with high frequency, the immunomodulation activities of rifaximin associated with a B. lactis resistant mutant were also taken into account. Data obtained from PBMC stimulation experiments suggest the following conclusions: (i) rifaximin does not exert any effect on production of IL-1β, IL-6 and IL-10, whereas it weakly stimulates production of TNF-α; (ii) B. lactis appears as a good inducer of IL-1β, IL-6 and TNF-α; (iii) combination of BI07-res and rifaximin exhibits a lower stimulation effect than BI07-res alone, especially for IL-6. These results confirm the potential anti-inflammatory effect of rifaximin, and are in agreement with several studies that report a transient pro-inflammatory response associated with probiotic administration. The understanding of the molecular factors determining rifaximin resistance in the genus Bifidobacterium assumes an applicative significance at pharmaceutical and medical level, as it represents the scientific basis to justify the simultaneous use of the antibiotic rifaximin and probiotic bifidobacteria in the clinical treatment of intestinal disorders.

Long-term dietary exposure to lead in young European children: comparing a pan-European approach with a national exposure assessment

Long-term dietary exposures to lead in young children were calculated by combining food consumption data of 11 European countries categorised using harmonised broad food categories with occurrence data on lead from different Member States (pan-European approach). The results of the assessment in children living in the Netherlands were compared with a long-term lead intake assessment in the same group using Dutch lead concentration data and linking the consumption and concentration data at the highest possible level of detail. Exposures obtained with the pan-European approach were higher than the national exposure calculations. For both assessments cereals contributed most to the exposure. The lower dietary exposure in the national study was due to the use of lower lead concentrations and...

Evaluation of Human Exposure to Magnetic Fields Generated by Electric Power Systems in Complex Configurations

The international growing concern for the human exposure to magnetic fields generated by electric power lines has unavoidably led to imposing legal limits. Respecting these limits, implies being able to calculate easily and accurately the generated magnetic field also in complex configurations. Twisting of phase conductors is such a case. The consolidated exact and approximated theory regarding a single-circuit twisted three-phase power cable line has been reported along with the proposal of an innovative simplified formula obtained by means of an heuristic procedure. This formula, although being dramatically simpler, is proven to be a good approximation of the analytical formula and at the same time much more accurate than the approximated formula found in literature. The double-circuit twisted three-phase power cable line case has been studied following different approaches of increasing complexity and accuracy. In this framework, the effectiveness of the above-mentioned innovative formula is also examined. The experimental verification of the correctness of the twisted double-circuit theoretical analysis has permitted its extension to multiple-circuit twisted three-phase power cable lines. In addition, appropriate 2D and, in particularly, 3D numerical codes for simulating real existing overhead power lines for the calculation of the magnetic field in their vicinity have been created. Finally, an innovative ‘smart’ measurement and evaluation system of the magnetic field is being proposed, described and validated, which deals with the experimentally-based evaluation of the total magnetic field B generated by multiple sources in complex three-dimensional arrangements, carried out on the basis of the measurement of the three Cartesian field components and their correlation with the field currents via multilinear regression techniques. The ultimate goal is verifying that magnetic induction intensity is within the prescribed limits.

Methodological approaches to estimate human population exposure to chemical substances

The public awareness that chemical substances are present ubiquitously in the environment, can be assumed through the diet and can exhibit various health effects, is very high in Europe and Italy. National and international institutions are called to provide figures on the magnitude, frequency, and duration of the population exposure to chemicals, including both natural or anthropogenic substances, voluntarily added to consumers’ good or accidentally entering the production chains. This thesis focuses broadly on how human population exposure to chemicals can be estimated, with particular attention to the methodological approaches and specific focus on dietary exposure assessment and biomonitoring. From the results obtained in the different studies collected in this thesis, it has been pointed out that when selecting the approach to use for the estimate of the exposure to chemicals, several different aspects must be taken into account: the nature of the chemical substance, the population of interest, clarify if the objective is to assess chronic or acute exposure, and finally, take into account the quality and quantity of data available in order to specify and quantify the uncertainty of the estimate.

Multiplex network analysis with application to biological high-throughput data

In questa tesi vengono studiate alcune caratteristiche dei network a multiplex; in particolare l'analisi verte sulla quantificazione delle differenze fra i layer del multiplex. Le dissimilarita sono valutate sia osservando le connessioni di singoli nodi in layer diversi, sia stimando le diverse partizioni dei layer. Sono quindi introdotte alcune importanti misure per la caratterizzazione dei multiplex, che vengono poi usate per la costruzione di metodi di community detection . La quantificazione delle differenze tra le partizioni di due layer viene stimata utilizzando una misura di mutua informazione. Viene inoltre approfondito l'uso del test dell'ipergeometrica per la determinazione di nodi sovra-rappresentati in un layer, mostrando l'efficacia del test in funzione della similarita dei layer. Questi metodi per la caratterizzazione delle proprieta dei network a multiplex vengono applicati a dati biologici reali. I dati utilizzati sono stati raccolti dallo studio DILGOM con l'obiettivo di determinare le implicazioni genetiche, trascrittomiche e metaboliche dell'obesita e della sindrome metabolica. Questi dati sono utilizzati dal progetto Mimomics per la determinazione di relazioni fra diverse omiche. Nella tesi sono analizzati i dati metabolici utilizzando un approccio a multiplex network per verificare la presenza di differenze fra le relazioni di composti sanguigni di persone obese e normopeso.

Effects of exposure to physical factors on homeopathic preparations as determined by ultraviolet light spectroscopy

Clinical trials have reported statistically significant and clinically relevant effects of homeopathic preparations. We applied ultraviolet (UV) spectroscopy to investigate the physical properties of homeopathic preparations and to contribute to an understanding of the not-yet-identified mode of action. In previous investigations, homeopathic preparations had significantly lower UV light transmissions than controls. The aim of this study was to explore the possible effects of external factors (UV light and temperature) on the homeopathic preparations. Homeopathic centesimal (c) dilutions, 1c to 30c, of copper sulfate (CuSO(4)), decimal dilutions of sulfur (S(8)), 1x to 30x, and controls (succussed potentization medium) were prepared, randomized, and blinded. UV transmission was measured at six different time points after preparation (from 4 to 256 days). In addition, one series of samples was exposed to UV light of a sterilization lamp for 12 h, one was incubated at 37 degrees Celsius for 24 h, and one was heated to 90 degrees Celsius for 15 min. UV light transmission values from 190 or 220 nm to 340 nm were measured several times and averaged. After each exposure, UV transmission of the homeopathic preparations of CuSO(4) was significantly reduced compared to the controls, particularly after heating to 37 degrees Celsius. Overall, the nonexposed CuSO(4) preparations did not show significantly lower UV transmission compared to controls; however, the pooled subgroup of measurements at days 26, 33, and 110 yielded significant differences. UV light transmission for S(8) preparations did not show any differences compared to controls. Our conclusion is that exposure to external factors, incubation at 37 degrees Celsius in particular, increases the difference in light transmission of homeopathic CuSO(4) preparations compared to controls.

Fire victim identification by post-mortem dental CT: Radiologic evaluation of restorative materials after exposure to high temperatures

The aim of this study was to evaluate the use of high resolution CT to radiologically define teeth filling material properties in terms of Hounsfield units after high temperature exposure.