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Byline: A. Margherita, G. Secundo, C. Taurino Emerging market and industry trends are reshaping substantially the critical variables which impact on the competitiveness of agrifood companies. Food producers, processors and distributors face new challenges related with the management of the whole supply chain. The increasing industry dynamism and complexity requires improved engineering and management capabilities for agribusiness leaders, related with the analysis of macroeconomic, consumption and distribution patterns as well as with the design and implementation of new models for managing operations and technology. In this paper, we present a framework for competencies building for agribusiness managers. A multidisciplinary approach is illustrated for the design of a curriculum targeted for executive education programmes. Starting from a definition for the agribusiness manager profile, and based on the review of both theory contributions and domain-specific education initiatives, we define a topics-based taxonomy of technical contents together with a set of learning objectives to be achieved for the profile.

Background: Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status., Methods: We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology., Results: Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = -0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress., Conclusions: Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease.

Background: Teicoplanin is a glycopeptide antibiotic used clinically in Europe and in Japan for the treatment of multi-resistant Gram-positive infections. It is produced by fermenting Actinoplanes teichomyceticus. The pharmaceutically active principle is teicoplanin A2, a complex of compounds designated T-A2-1-A2-5 differing in the length and branching of the fatty acid moiety linked to the glucosamine residue on the heptapeptide scaffold. According to European and Japanese Pharmacopoeia, components of the drug must be reproduced in fixed amounts to be authorized for clinical use., Results: We report our studies on optimizing the fermentation process to produce teicoplanin A2 in A. teichomyceticus ATCC 31121. Robustness of the process was assessed on scales from a miniaturized deep-well microtiter system to flasks and 3-L bioreactor fermenters. The production of individual factors T-A2-1-A2-5 was modulated by adding suitable precursors to the cultivation medium. Specific production of T-A2-1, characterized by a linear C10:1 acyl moiety, is enhanced by adding methyl linoleate, trilinoleate, and crude oils such as corn and cottonseed oils. Accumulation of T-A2-3, characterized by a linear C10:0 acyl chain, is stimulated by adding methyl oleate, trioleate, and oils such as olive and lard oils. Percentages of T-A2-2, T-A2-4, and, T-A2-5 bearing the iso-C10:0, anteiso-C11:0, and iso-C11:0 acyl moieties, respectively, are significantly increased by adding precursor amino acids L-valine, L-isoleucine, and L-leucine. Along with the stimulatory effect on specific complex components, fatty acid esters, oils, and amino acids (with the exception of L-valine) inhibit total antibiotic productivity overall. By adding industrial oils to medium containing L-valine the total production is comparable, giving unusual complex compositions., Conclusions: Since the cost and the quality of teicoplanin production depend mainly on the fermentation process, we developed a robust and scalable fermentation process by using an industrial medium in which a complex composition can be modulated by the combined addition of suitable precursors. This work was performed in the wild-type strain ATCC 31121, which has a clear genetic background. This is important for starting a rational improvement program and also helps to better control teicoplanin production during process and strain development.

Owing to the dynamic nature of the transcriptome, gene expression profiling is a promising tool for discovery of disease-related genes and biological pathways. In the present study, we examined gene expression in whole blood of 12 patients with CAD (coronary artery disease) and 12 healthy control subjects. Furthermore, ten patients with CAD underwent whole-blood gene expression analysis before and after the completion of a cardiac rehabilitation programme following surgical coronary revascularization. mRNA and miRNA (microRNA) were isolated for expression profiling. Gene expression analysis identified 365 differentially expressed genes in patients with CAD compared with healthy controls (175 up- and 190 down-regulated in CAD), and 645 in CAD rehabilitation patients (196 up- and 449 down-regulated post-rehabilitation). Biological pathway analysis identified a number of canonical pathways, including oxidative phosphorylation and mitochondrial function, as being significantly and consistently modulated across the groups. Analysis of miRNA expression revealed a number of differentially expressed miRNAs, including hsa-miR-140-3p (control compared with CAD, P=0.017), hsa-miR-182 (control compared with CAD, P=0.093), hsa-miR-92a and hsa-miR-92b (post- compared with pre-exercise, P<0.01). Global analysis of predicted miRNA targets found significantly reduced expression of genes with target regions compared with those without: hsa-miR-140-3p (P=0.002), hsa-miR-182 (P=0.001), hsa-miR-92a and hsa-miR-92b (P=2.2x10-16). In conclusion, using whole blood as a 'surrogate tissue' in patients with CAD, we have identified differentially expressed miRNAs, differentially regulated genes and modulated pathways which warrant further investigation in the setting of cardiovascular function. This approach may represent a novel non-invasive strategy to unravel potentially modifiable pathways and possible therapeutic targets in cardiovascular disease.

Objective: To evaluate the influence of plasma catecholamines on the vascular structure in humans, the effects of catecholamine normalization on the carotid wall of patients with phaeochromocytoma (PHEO) were investigated. A prospective study in patients with PHEO before and after (first follow-up: 20.5+/-1.8 months, second follow-up: 31.5+/-2.2 months) successful surgery was conducted in the University Referral Center for Blood Pressure Diseases. Ten consecutive patients with PHEOs and ten age- and blood pressure-matched controls were investigated. Intima-media thickness (IMT) by two-dimensional conventional ultrasonography and corrected ultrasonic integrated backscatter signal (C-IBS) analysis of carotid arteries were investigated in basal conditions and after mass removal., Results: In PHEOs, at variance with the expected reduction in metanephrines and catecholamines, no variation in body weight, blood pressure and lipid profile was observed after operation. IMT and C-IBS values in patients with PHEO were greater (at least P<0.01) than in controls. At long-term follow-up after surgery, a significant reduction in mean carotid IMT (P<0.0009) and C-IBS (P<0.009) values was observed. A significant correlation (r=0.54, P<0.03) was found between absolute reduction in C-IBS values and absolute decrement in urinary normetanephrine levels., Conclusions: Our study shows that normalization of catecholamine levels after the removal of PHEO improves carotid IMT and reduces carotid wall fibrosis even without influencing blood pressure and lipid profile. These findings confirm that high catecholamine tone in humans directly influences vascular remodelling of carotid arteries.

Objective: It is well known that vascular and cardiac structure may be influenced by circulating neurohormonal factors. Our aim was to study the myocardial wall texture by integrated backscatter (IBS) analysis in patients with phaeochromocytoma (PHEO)., Design: Fourteen patients with PHEO, 15 matched high-normal blood pressure (BP) subjects, 15 mild essential hypertensives and 15 normotensive controls underwent two-dimensional conventional ultrasonography and ultrasonic IBS of the myocardial wall. IBS analysis was performed at both interventricular septum and posterior wall levels. IBS values were expressed in decibels and corrected for the IBS values obtained within the pericardium (C-IBS). The systo-diastolic cyclical variations in IBS (CV-IBS), an index of myocardial contractile performance, were also evaluated., Results: Patients with PHEO showed C-IBS values comparable to those of hypertensive patients, and significantly higher than those of high-normal BP subjects and controls at both septum and posterior wall levels (P < 0.001 for all). In PHEO patients, CV-IBS was lower than that of normotensive, high-normal BP subjects and hypertensive patients, at both septum and posterior wall levels (P < 0.001 for all). An inverse relationship was found in the PHEO group between 24-h urinary normetanephrine and CV-IBS of both septum (r(2) = -0.29, P < 0.05) and posterior wall (r(2) = -0.46, P < 0.05)., Conclusions: Our results show that patients with PHEO have myocardial remodelling characterized by increased myocardial fibrosis, confirmed by an increase in the overall myocardial backscatter level measured. The observed decrease in the magnitude of CV-IBS suggests an impairment of myocardial contractile performance. These results may provide insights into the role of catecholamines in left ventricular (LV) structure and function in PHEO.

Context: The influence of catecholamines on vascular remodeling in humans was investigated., Objective: The objective was to study the carotid vascular wall in patients with pheochromocytoma (PHEO)., Design and Setting: An observational study was conducted in a university referral center for blood pressure diseases., Patients: Fourteen patients with PHEO, 15 matched high-normal essential hypertensives, 15 mild essential hypertensives, and 15 controls underwent two-dimensional conventional ultrasonography and ultrasonic tissue characterization of the carotid wall., Main Outcome Measures: Intimal media thickness (IMT), diameter, and corrected ultrasonic integrated backscatter signal (C-IBS) of carotid arteries were evaluated., Results: IMT in PHEOs (0.844 +/- 0.18 mm, mean +/- sd) was greater than not only controls (0.596 +/- 0.09 mm, P < 0.0002) but also high-normal (0.710 +/- 0.17 mm, P < 0.03), and even mild (0.727 +/- 0.20 mm, P = 0.06) hypertensives. IMT in the latter was higher than in controls (P < 0.03), without difference in comparison with high-normal hypertensives. C-IBS values in PHEOs (-21.71 +/- 2.0 dB, mean +/- sd) were greater than in controls (-26.20 +/- 1.73 dB, P < 0.0001) but also than in high-normal (-23.84 +/- 1.16 dB, P < 0.002) and mild (-23.37 +/- 1.99 dB, P < 0.01) hypertensives. C-IBS values in controls were lower than in high-normal (P < 0.0005) and mild (P < 0.0001) hypertensives. Carotid diameter was not significantly different in the four groups. In PHEOs, C-IBS was associated with urinary noradrenaline (r = 0.640, P < 0.01) and normethanephrine (r = 0.737, P < 0.009)., Conclusions: Carotid IMT of PHEOs is higher than in controls and matched groups of hypertensives with comparable or even higher blood pressure. This vascular rearrangement is characterized by increased IBS values due to collagen deposition and vascular fibrosis. Therefore, our data show that abnormal catecholamine levels take part per se in carotid wall remodeling of patients with PHEO.

Context: The contribution of endogenous testosterone (TS) in the functional integrity of peripheral circulation in men was studied., Objective: The objective of this study was to observe vascular reactivity in male congenital hypogonadal patients before and after prolonged exposure to normal TS levels., Design: This was a longitudinal study in which, basically and after 6-month (range, 6-8 months) androgen treatment, we investigated forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (Ach), alone or in the presence of N(G)-monomethyl-l-arginine infusion, and by sodium nitroprusside. We also evaluated, by Doppler ultrasound, flow-mediated dilation of the brachial artery (BA) in response to reactive hyperemia (RH) and glyceryl trinitrate (GTN)., Setting: The studies were conducted at university referral centers for andrologic and blood pressure diseases., Patients: Eight adult male Caucasian hypogonadal patients and nine healthy matched control subjects were studied., Intervention: Intervention was TS enanthate (250 mg in 1 ml oily solution) by im injection every 3 wk., Results: At baseline, BA diameter and RH, flow-mediated dilation, and GTN responses showed no difference between the two groups. TS therapy increased plasma total TS (P < 0.02) and reduced high-density lipoprotein (P < 0.01) and total cholesterol (P < 0.04). It did not affect vasodilation to sodium nitroprusside (355 +/- 47%), but it further reduced the vascular response to Ach (187 +/- 29%, P < 0.01 vs. baseline) and abolished the inhibition by N(G)-monomethyl-l-arginine on Ach (inhibition, 3.2%). Moreover, TS therapy decreased (P < 0.01) flow-mediated dilation, whereas it did not modify BA diameter and responses to RH and GTN., Conclusions: Hypogonadal patients show impaired vascular reactivity, including endothelial-dependent vasodilation due to reduced nitric oxide availability. TS administration further impairs nitric oxide availability in these patients.