Production of Alfalfa Seed in Italy

Alfalfa (Medicago sativa) is considered the largest cultivated forage species in the temperate areas in the world and in Italy covers about 700,000 ha. This species is important for the ability to produce a good quality forage with low input. Alfalfa seed production is spread throughout Italy, France and Spain (Fig. 1). In Italy, about 47% of forage area is planted with alfalfa and the Italian regions where alfalfa seed is mainly produced are Emilia Romagna, Marche and Tuscany (Fig. 2). In 2012 the area for the production of alfalfa seed was 20,906 ha with a seed production of 9,006 tons

Fusarium head blight on barley: etiology and characterization of Fusaria producers of mycotoxins

FHB dell’orzo è una malattia dall’eziologia complessa causata da specie fungine tossigene appartenenti al genere Fusarium in grado di compromettere interi raccolti. La predominanza di una specie di Fusarium rispetto ad un’altra dipende principalmente dal clima. Con i cambiamenti climatici in corso si sta assistendo ad una modificazione delle popolazioni fungine e per questo risulta fondamentale monitorare le specie fungine presenti in una determinata coltura, onde prevenire micotossicosi per l’uomo ed animali. Da analisi micologiche su granella di orzo proveniente da varie regioni italiane F. graminearum, F. poae e F. tricinctum sono risultate le specie più presenti. Prove in ambiente controllato hanno consentito di mettere a punto una scala fitopatometrica per la valutazione di FHB. Tale scala risulta pratica e facilmente applicabile ed è stata utilizzata per le prove di campo. In queste prove oltre a FHB sono stati valutati altri parametri quali produzione e contaminazione da micotossine. Il contenuto di micotossina Deossinivalenolo è correlata alla frequenza di F. graminearum su granella. I dati produttivi delle tesi inoculate non sono apparsi significativamente distinti dalle tesi non inoculate, facendo dedurre che granella contaminata da micotossina possa facilmente ritrovarsi nelle derrate alimentari, in quanto le cariossidi infette, solo lievemente più leggere di quelle sane. vengono ugualmente raccolte e commercializzate con serie conseguenze per l’industria mangimistica e alimentare. Con il presente lavoro si è dimostrato per la prima volta che per effetto della colonizzazione di culmi di piante di orzo da parte di tre specie Fusarium, responsabili sia della fusariosi del piede che della spiga, la micotossina DON può traslocare dalla base delle piante fino alla spiga, mentre la presenza dei funghi è rilevata da alte concentrazioni fino al secondo nodo. Da questo emerge che la presenza di Fusarium a livello basale contribuisce alla contaminazione della granella, oltre a quella dovuta ad FHB.Fusarium head blight (FHB) is a barley disease with a complex etiology which is caused by different toxigenic Fusarium species able to compromise the whole crop yield. Climatic conditions establish the predominance of one Fusarium species respect to the others. With the climate change in progress we are attending to a modification of fungal populations that evidence the importance of monitoring the presence of fungal species in the crop, to prevent mycotoxicosis, dangerous for humans and animals. Mycological analysis in barley kernel from different Italian regions has shown that F. graminearum, F. poae and F. tricinctum are the main species. A phytopathometric scale to evaluate FHB was set up in controlled conditions. That scale, practical and easy to use, was used in field trials, where FHB, yield and mycotoxin contamination were evaluated. Mycotoxin DON content was correlated to F. graminearum frequency. Yield data of inoculated plots were not significant respect to the not inoculated ones, this implies that it is easy to find kernel contaminated by mycotoxins in food and feed, because infected grains are slightly lighter than those not infected and they are harvested and commercialized as well with serious consequences to public safety. For the first time on barley, with this study it was shown that after culm colonization of the plant by three toxigenic Fusarium spp., able to cause both FHB and FCR, DON mycotoxin can be transferred from the bottom to the head, whereas the presence of the fungi was with high level until the second node. This means that presence of Fusarium at base level contributes to the kernel contamination, additionally to FHB

Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: A pilot study

Background: Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms. Methods: Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceryl trinitrate administration. Differences were analysed by repeated measures ANOVA, considering treatment as between factor and time as within factor; Bonferroni post hoc comparison test was also used. Results: Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium were also increased. 24 h urinary sodium and fasting blood glucose were unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes. Flow-mediated dilation was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05), even after correction for mean BP. Renal resistive index was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05). These vascular modifications were not observed in hydrochlorothiazide-treated individuals. Conclusions: An acute treatment with dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in BP and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction

TDP-43 deficiency links Amyotrophic Lateral Sclerosis with R-loop homeostasis and R loop-mediated DNA damage

TDP-43 is a DNA and RNA binding protein involved in RNA processing and with structural resemblance to heterogeneous ribonucleoproteins (hnRNPs), whose depletion sensitizes neurons to double strand DNA breaks (DSBs). Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, in which 97% of patients are familial and sporadic cases associated with TDP-43 proteinopathies and conditions clearing TDP-43 from the nucleus, but we know little about the molecular basis of the disease. Here, we prove that mislocalization of mutated TDP-43 (A382T) in transfected neuronal SH-SY5Y and lymphoblastoid cell lines (LCLs) from an ALS patient cause R-loop accumulation, and R loop-dependent increased DSBs and Fanconi Anemia repair centers. Similar results were observed in a non-neuronal model of HeLa cells depleted of TDP-43. These results uncover a new role of TDP-43 in the control of co-transcriptional R-loops and the maintenance of genome integrity by preventing harmful R-loop accumulation. Our findings thus link TDP-43 pathology to increased R-loops and R loop-mediated DNA damage opening the possibility that R-loop modulation in TDP-43-defective cells might help develop ALS therapies

Diagnostic accuracy of quantitative susceptibility mapping in multiple system atrophy: The impact of echo time and the potential of histogram analysis

The non-invasive quantification of iron stores via Quantitative Susceptibility Mapping (QSM) could play an important role in the diagnosis and the differential diagnosis of atypical Parkinsonisms. However, the susceptibility (χ) values measured via QSM depend on echo time (TE). This effect relates to the microstructural organization within the voxel, whose composition can be altered by the disease. Moreover, pathological iron deposition in a brain area may not be spatially uniform, and conventional Region of Interest (ROI)-based analysis may fail in detecting alterations. Therefore, in this work we evaluated the impact of echo time on the diagnostic accuracy of QSM on a population of patients with Multiple System Atrophy (MSA) of either Parkinsonian (MSAp) or cerebellar (MSAc) phenotypes. In addition, we tested the potential of histogram analysis to improve QSM classification accuracy. We enrolled 32 patients (19 MSAp and 13 MSAc) and 16 healthy controls, who underwent a 7T MRI session including a gradient-recalled multi-echo sequence for χ mapping. Nine histogram features were extracted from the χ maps computed for each TE in atlas-based ROIs covering deep brain nuclei, and compared among groups. Alterations of susceptibility distribution were found in the Putamen, Substantia Nigra, Globus Pallidus and Caudate Nucleus for MSAp and in the Substantia Nigra and Dentate Nucleus for MSAc. Increased iron deposition was observed in a larger number of ROIs for the two shortest TEs and the standard deviation, the 75th and the 90th percentile were the most informative features yielding excellent diagnostic accuracy with area under the ROC curve > 0.9. In conclusion, short TEs may enhance QSM diagnostic performances, as they can capture variations in rapidly-decaying contributions of high χ sources. The analysis of histogram features allowed to reveal fine heterogeneities in the spatial distribution of susceptibility alteration, otherwise undetected by a simple evaluation of ROI χ mean values

Is it still worthwhile to perform quarterly CD4+ T lymphocyte cell counts on HIV-1 infected stable patients?

Background: In the last twenty years routine T CD4+ lymphocyte (CD4) cell count has proved to be a key factor to determine the stage of HIV infection and start or discontinue of prophylaxis for opportunistic infections. However, several studies recently showed that in stable patients on cART a quarterly CD4 cell count monitoring results in limited (or null) clinical relevance. The research is intended to investigate whether performing quarterly CD4 cell counts in stable HIV-1 patients is still recommendable and to provide a forecast of the cost saving that could be achieved by reducing CD4 monitoring in such a category of patients. Methods: The study is based on data referring to all HIV-infected patients > 18 years of age being treated at two infectious diseases units located in the metropolitan area of Genoa, Italy. The probability of CD4 cell counts dropping below a threshold value set at 350 cells/mm3 is assessed using confidence intervals and Kaplan-Meier survival estimates, whereas multivariate Cox analysis and logistic regression are implemented in order to identify factors associated with CD4 cell count falls below 350 cells/mm3. Results: Statistical analysis reveals that among stable patients the probability of maintaining CD4 >350 cell/mm3 is more than 98%. Econometric models indicate that HCV co-infection and HIV-RNA values >50 copies/mL in previous examinations are associated with CD4 falls below 350 cells/mm3. Moreover, results suggest that the cost saving that could be obtained by reducing CD4 examinations ranges from 33% to 67%. Conclusions: Empirical findings show that patients defined as stable at enrollment are highly unlikely to experience a CD4 value <350 cell/mm3 in the space/arc of a year. The research supports a recommendation for annual CD4 monitoring in stable HIV-1 patients

Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients

Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset neurodegenerative disease, that affects cortical, bulbar and spinal motor neurons, and it is considered a proteinopathy, in which pathological proteins (SOD1, TDP-43, and FUS) may accumulate and interfere with neuronal functions eventually leading to cell death. These proteins can be released from cells and transported in the body fluids by extracellular vesicles (EVs). EVs are spherical vesicles, which are classified mainly in microvesicles (MVs) and exosomes (EXOs) based on their biogenesis, size and surface markers. In this study we characterized MVs and EXOs isolated from plasma of sporadic ALS patients and healthy controls and determined their number, size and SOD1, TDP-43, and FUS protein composition. No variation was found in the number of EVs between ALS patients and controls. However, the mean size both for MVs and for EXOs resulted increased in ALS patients compared to controls. MVs derived from ALS patients were enriched in SOD1, TDP-43, phospho-TDP-43, and FUS proteins compared to CTRLs. SOD1 was generally more concentrated in EXOs than in MVs, while TDP-43 and FUS protein levels were slightly higher in MVs than in EXOs. We demonstrated that MVs and EXOs size were increased in ALS patients compared to controls and that MVs of ALS patients were enriched with toxic proteins compared to CTRLs. EXOs did not show any protein changes. These data may suggest that MVs can transport toxic proteins and might play a role in prion-like propagation of ALS disease

Compartmental tongue surgery for intermediate-advanced squamous cell carcinoma: A multicentric study

Background: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). Methods: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. Results: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). Conclusion: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC

Leukocyte Derived Microvesicles as Disease Progression Biomarkers in Slow Progressing Amyotrophic Lateral Sclerosis Patients

The lack of biomarkers in Amyotrophic Lateral Sclerosis (ALS) makes it difficult to determine the stage of the disease in patients and, therefore, it delays therapeutic trials. Microvesicles (MVs) are possible biomarkers implicated in physiological and pathological functions, however, their role in ALS remains unclear. We investigated whether plasma derived microvesicles could be overrepresented in a group of 40 patients affected by ALS compared to 28 Alzheimer’s Disease (AD) patients and 36 healthy volunteers. Leukocyte derived MVs (LMVs) compared to endothelial, platelet, erythrocyte derived MVs, were mostly present in ALS patients compared to AD patients and healthy donors. Correlation analysis corrected for the presence of confounding variables (riluzole, age at onset, site of onset, gender) was tested between PRL (Progression Rate at the Last visit) and LMVs, and a statistically significant value was found (Pearson partial correlation r = 0.407, p = 0.006). We also investigated SOD1, TDP-43 intravesicular protein level in LMVs. Misfolded SOD1 was selectively transported by LMVs and its protein level was associated with the percentage of LMVs in slow progressing patients (r = 0.545, p = 0.033). Our preliminary findings suggest that LMVs are upregulated in ALS patients and they can be considered possible markers of disease progression