VALUTAZIONE DEL RINFORZO RADICALE DEL SUOLO OPERATO DALLE RADICI DELLE PRINCIPALI SPECIE FORESTALI DELLA LOMBARDIA

Forests can prevent and/or mitigate hydrogeomorphic hazards in mountainous landscapes. Their effect is particularly relevant in the case of shallow landslides phenomena, where plants decrease the water content of the soil and increase its mechanical strength. Although such an effect is well known from ages, its quantification is a relatively new challenge. The present dissertation faces the effect on hillslope stability of several forest species typical of Lombardy\u2019s mountain forests. Such effects are estimate in terms of additional root cohesion by the classical Wu (1976) and Waldron (1977) model (W&W) and by Fiber Bundle Model approach (FBM). Samples of European beech (Fagus sylvatica L.), Norway spruce (Picea abies (L.) Karst.), European larch (Larix decidua Mill.), sweet chestnut (Castanea sativa Mill.) and European hop-hornbeam (Ostrya carpinifolia Scop.), Sycamore Maple (Acer pseudoplatanus L.), Grey Alder or Speckled Alder (Alnus incana (L.) Moench), European Ash (Fraxinus excelsior L.), Manna Ash (Fraxinus ornus L.), Black Locust (Robinia pseudoacacia L.), were taken in different locations of Lombardy (Northern Italy) to estimate root tensile strength, Root Area Ratio the root cohesion distribution within the soil. Besides the increasing of knowledge concerning the ability of the mentioned species to reinforce soils, that are fundamental to estimate the stability of forested hillslopes in the Alps, the dissertation reaches some more general results. Referring to root tensile strength, the obtained results confirm that such property is related to root size by a power law relationship. Such relationship, however, is not invariant with species but shows dependence with site\u2019s characteristics, although the observed variability is very high and no specific factor has been resulted as a key factor. Considering roots with a diameter greater than 1 mm, European beech roots seem to be more resistant than Norway spruce, Sweet chestnut and European Ash. Referring to Root Area Ratio, the results herein presented showed a great variability within the same species at the same location and among different locations. Despite the number of rooted profiles investigated, such variability hindered the possibility to identify a specie-specific or site-specific behaviour. Concerning root cohesion modelling, the original W&W model seems to overestimate root reinforcement because it assumes that all the roots crossing the shear surface break at the same time. FBM approach, instead, accounting for the progressive breaking of roots represents a promising perspective in root cohesion evaluation. Root cohesion values present the same species and site variability according to RAR values. The values herein obtained, moreover, are consistent with the results of direct shear tests and back-analysis data and, finally, they are significant for slope stabilisation at depth where shallow landslides generally occur

Treatment of rheumatoid arthritis with anti-tumor necrosis factor or tocilizumab therapy as first biologic in a global comparative observational study

Objective To compare clinical effectiveness between tocilizumab and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional synthetic disease-modifying antirheumatic drugs initiating biologic therapy. Methods Patients prescribed tocilizumab (intravenous) or TNFi were prospectively observed in routine clinical practice for 52 weeks across 158 sites in 26 countries. The primary observation was the change from baseline in Disease Activity Score based on 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) at week 24 using analysis of covariance for between-groups comparison. Secondary end points included Clinical Disease Activity Index (CDAI) and patient-reported outcomes at weeks 24 and 52. Results Of 1,216 patients, 35% initiated tocilizumab and 65% initiated TNFi. RA duration was shorter, and disease activity and corticosteroid use were higher in tocilizumab patients. Tocilizumab-treated patients had greater improvement in DAS28-ESR at weeks 24 and 52 (week 24 difference [95% confidence interval] in adjusted means: −0.831 [−1.086, −0.576]; P < 0.001). Change from baseline in CDAI was also greater with tocilizumab (adjusted means difference: week 24, −3.48; week 52, −4.60; both P < 0.001). Tocilizumab-treated patients had more improvement in the Health Assessment Questionnaire disability index than TNFi-treated patients (P < 0.05). The cumulative probability of drug discontinuation at week 52 was lower with tocilizumab (15%) than TNFi (27%; P < 0.001, unadjusted analysis). Unadjusted frequencies (events per 100 patient-years) for tocilizumab and TNFi were 6.44 and 11.99 for serious adverse events, 1.98 and 5.03 for serious infections, and 0.74 and 0.77 for deaths, respectively. Conclusion Patients initiating tocilizumab experienced greater effectiveness and drug survival than those initiating TNFi in an observational setting

Effects of combined drug treatments on Plasmodium falciparum : in vitro assays with doxycycline, ivermectin and efflux pump inhibitors

There is great concern regarding the rapid emergence and spread of drug-resistance in Plasmodium falciparum, the parasite responsible for the most severe form of human malaria. Parasite populations resistant to some or all the currently available antimalarial treatments are present in different world regions. Considering the need for novel and integrated approaches to control malaria, combinations of drugs were tested on P. falciparum. The primary focus was on doxycycline, an antibiotic that specifically targets the apicoplast of the parasite. In combination with doxycycline, three different drugs known to inhibit efflux pumps (verapamil, elacridar and ivermectin) were tested, with the assumption that they could increase the intracellular concentration of the antibiotic and consequently its efficacy against P. falciparum. We emphasize that elacridar is a third-generation ABC transporters inhibitor, never tested before on malaria parasites. In vitro experiments were performed on asexual stages of two strains of P. falciparum, chloroquine-sensitive (D10) and chloroquineresistant (W2). Incubation times on asynchronous or synchronous cultures were 72h or 96h, respectively. The antiplasmodial effect (i.e. the IC50) was determined by measuring the activity of the parasite lactate dehydrogenase, while the interaction between drugs was determined through combination index (CI) analyses. Elacridar achieved an IC50 concentration comparable to that of ivermectin, approx. 10-fold lower than that of verapamil, the other tested ABC transporter inhibitor. CI results showed synergistic effect of verapamil plus doxycycline, which is coherent with the starting hypothesis, i.e. that ABC transporters represent potential targets, worth of further investigations, towards the development of companion molecules useful to enhance the efficacy of antimalarial drugs. At the same time, the observed antagonistic effect of doxycycline in combination with ivermectin or elacridar highlighted the importance of drug testing, to avoid the de-facto generation of a sub-dosage, a condition that facilitates the development of drug resistance

Genetic variability of Haemonchus contortus (Nematoda: Trichostrongyloidea) in alpine ruminant host species

Genetic variability of the ovine parasite Haemonchus contortus from the Alpine area was investigated using mitochondrial DNA (nd4 gene), internal transcribed spacers 1 and 2 and microsatellites, in order to assess whether cross-transmission between domestic and wild ruminants occurs. The dataset was composed of 78 individual adult male H. contortus collected from chamois (Rupicapra r. rupicapra), roe deer (Capreolus capreolus), alpine ibex (Capra ibex ibex), domestic goat (Capra hircus) and sheep (Ovis aries) from different alpine areas. The data obtained show low host specificity and high genetic variation within H. contortus populations. The analyses indicate the presence of two mitochondrial haplotype clusters among host species and the absence of cryptic parasite species, confirming H. contortus as a generalist nematode and suggesting that parasite transmission between populations of domestic and wild ruminants normally occurs

Multilevel examination of minor salivary gland biopsy for Sjögren's syndrome significantly improves diagnostic performance of AECG classification criteria

The recently observed low reproducibility of focus score (FS) assessment at different section depths in a series of single minor salivary gland biopsies highlighted the need for a standardized protocol of extensive histopathological examination of such biopsies in Sjögren's syndrome. For this purpose, a cumulative focus score (cFS) was evaluated on three slides cut at 200-μm intervals from each of a series of 120 salivary biopsies. The cFS was substituted for the baseline FS in the American–European Consensus Group (AECG) criteria set for Sjögren's syndrome classification, and then test specificity and sensitivity were assessed against clinical patient re-evaluation. Test performances of the AECG classification with the original FS and the score obtained after multilevel examination were statistically compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance of AECG classification significantly improved when the cFS was entered in the AECG classification; the improvement was mostly due to increased specificity in biopsies with a baseline FS ≥ 1 but <2. The assessment of a cFS obtained at three different section levels on minor salivary gland biopsies can be useful especially in biopsies with baseline FSs between 1 and 2

The choreography of the chemical defensome response to insecticide stress: insights into the Anopheles stephensi transcriptome using RNA-Seq

Animals respond to chemical stress with an array of gene families and pathways termed "chemical defensome". In arthropods, despite many defensome genes have been detected, how their activation is arranged during toxic exposure remains poorly understood. Here, we sequenced the transcriptome of Anopheles stephensi larvae exposed for six, 24 and 48 hours to the LD50 dose of the insecticide permethrin to monitor transcriptional changes of defensome genes across time. A total of 177 genes involved in insecticide defense were differentially expressed (DE) in at least one time-point, including genes encoding for Phase 0, I, II, III and antioxidant enzymes and for Heat Shock and Cuticular Proteins. Three major patterns emerged throughout time. First, most of DE genes were down-regulated at all time-points, suggesting a reallocation of energetic resources during insecticide stress. Second, single genes and clusters of genes turn off and on from six to 48 hours of treatment, showing a modulated response across time. Third, the number of up-regulated genes peaked at six hours and then decreased during exposure. Our results give a first picture of how defensome gene families respond against toxicants and provide a valuable resource for understanding how defensome genes work together during insecticide stress

A rapid qPCR method to investigate the circulation of the yeast Wickerhamomyces anomalus in humans

The yeast Wickerhamomyces anomalus has been proposed for many biotechnological applications in the food industry. However, a number of opportunistic pathogenic strains have been reported as causative agents of nosocomial fungemia. Recognition of potentially pathogenic isolates is an important challenge for the future commercialization of this yeast. The isolation of W. anomalus from different matrices and, recently, from mosquitoes, requires further investigations into its circulation in humans. Here we present a qPCR protocol for the detection of W. anomalus in human blood samples and the results of a screening of 525 donors, including different classes of patients and healthy people