Pierpaolo Cavallo

A novel fungal metabolite with beneficial properties for agricultural applications.

Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA) is a T. harzianum metabolite able to promote plant growth and strongly bind iron. In this work, we isolated from the culture filtrate of a T. harzianum strain a new metabolite, named isoharzianic acid (iso-HA), a stereoisomer of HA. The structure and absolute configuration of this compound has been determined by spectroscopic methods, including UV-Vis, MS, 1D and 2D NMR analyses. In vitro applications of iso-HA inhibited the mycelium radial growth of Sclerotinia sclerotiorum and Rhizoctonia solani. Moreover, iso HA improved the germination of tomato seeds and induced disease resistance. HPLC-DAD experiments showed that the production of HA and iso HA was affected by the presence of plant tissue in the liquid medium. In particular, tomato tissue elicited the production of HA but negatively modulated the biosynthesis of its analogue iso-HA, suggesting that different forms of the same Trichoderma secondary metabolite have specific roles in the molecular mechanism regulating the Trichoderma plant interaction.

Multiple gut–liver axis abnormalities in children with obesity with and without hepatic involvement

Gut–liver axis (GLA) dysfunction appears to play a role in obesity and obesity‐related hepatic complications.

Network analysis of drug prescriptions.

Networks exist in many different aspects of the world, at social, economical, biological, and molecular levels. Network science studies their parameters, or quantitative indicators; its instruments make it possible to draw and analyze networks from a mathematical perspective.

Population-based dose–response curve of glomerular filtration rate to dietary protein intake

BACKGROUND Kidney function measured as estimated glomerular filtration rate (eGFR) is a risk factor for mortality and severe diseases. Protein intake up-regulates kidney function. The dose-response curve of eGFR over protein intake is unknown. Urinary urea nitrogen is an objective index of protein intake. METHODS The study cross-sectionally analysed the relation between overnight urinary urea nitrogen ((on)U-ureaN) and eGFR with and without control for other variables in 4106 adults of the Gubbio population. Analyses were done for serum creatinine (S-cr) also to investigate the independency of results from eGFR calculation. RESULTS Higher (on)U-ureaN associated with higher eGFR, and lower S-cr independently of sex and age (simple and partial correlation coefficients >0.100, P < 0.001). Analyses by (on)U-ureaN decile indicated sigmoid curves of eGFR and S-cr over (on)U-ureaN with trend to flatness in the lowest 20% and the highest 20% of (on)U-ureaN (<5.19 and >10.12 mg/h, respectively). Multi-variable spline regression indicated that the relation of eGFR over (on)U-ureaN was non-significant for (on)U-ureaN <5.19 mg/h (coefficient = +0.27, 95% CI = -0.31/+0.84, P = 0.364), positive for (on)U-ureaN in the range 5.19-10.12 mg/h (coefficients = 1.35-1.64, lower 95% CI ≥ +0.48, P ≤ 0.002), and non-significant for (on)U-ureaN >10.12 mg/h (coefficient = +0.05, 95% CI = -0.06/ +0.16, P = 0.394). eGFR differed by ≈8 mL/min × 1.73 m(2) between the lowest and highest 20% of (on)U-ureaN distribution. CONCLUSIONS Higher protein intake relates to higher eGFR. The relation is sigmoid with eGFR up-regulation for (on)U-ureaN >5.19 mg/h, a threshold approximately corresponding to the recommended daily allowance for protein intake (0.8 g/day per kg of ideal weight).

Effects of bed-rest on urea and creatinine: correlation with changes in fat-free mass.

Background Bed-rest experiments are designed for investigation on catabolic effects of hypokinetic conditions and/or for microgravity simulation in on-ground aerospace research. Bed-rest effects include a reduction in fat-free mass and muscle mass. Urea and creatinine are catabolites of endogenous protein and of muscular energetic metabolism which are excreted mainly by the kidney. The study investigated on urea, creatinine, and kidney function during bed-rest. Methods Twenty healthy young men underwent a 7-day adaptation period (day-6 to day-0) and a 35-day bed-rest experiment (day1 to day35) during normocaloric diet. Urine were collected from day-3 to day0 (baseline) and from day1 to day35. Blood samples and anthropometrical data were collected at day0 (baseline) and bed-rest days 7, 14, 21, 28, and 35. Results Bed-rest reduced plasma volume, weight, fat-free mass, and muscle mass (P<0.001). During bed-rest there was a transient increase in plasma and urinary urea, a decrease in plasma creatinine, and no change in urinary creatinine. The overall integral of changes from day0 to day35 was on average +101.7 mg/dL for plasma urea (95%CI = +43.4/+159.9), +82.2 g/24 h for urinary urea (95%CI = +55.8/+108.7), −2.5 mg/dL for plasma creatinine (95%CI = −3.1/−1.9). Bed-rest reduced plasma cistatyn C also, which was used as mass-independent marker of glomerular filtration rate (−13.1%, P<0.05). Correlations with final reduction in fat-free mass and muscle mass were significant for the overall integral of changes in urinary urea from day0 to day35 (R = 0.706, P<0.001) and for early changes in urinary urea and plasma urea from day0 to day7 (R = 0.566, P = 0.009 and R = 0.715, P<0.001, respectively). Conclusions Study results shows that urea is a marker of catabolic conditions secondary to hypokinetic conditions.

Role of BAG3 in cancer progression: A therapeutic opportunity

BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility. A secreted form of BAG3 has been identified in studies on pancreatic ductal adenocarcinoma (PDAC). Secreted BAG3 can bind to a specific receptor, IFITM2, expressed on macrophages, and induce the release of factors that sustain tumour growth and the metastatic process. BAG3 neutralisation therefore appears to constitute a novel potential strategy in the therapy of PDAC and, possibly, other tumours.

A multicenter study on the appropriateness of hospitalization in obstetric wards:application of Obstetric Appropriateness Evaluation Protocol (Obstetric AEP)

Abstract The cross-sectional study has been based on the implementation of the Obstetric Appropriateness Evaluation Protocol (OAEP) in seven hospitals to determine inappropriate hospital admissions and days of stay. The outcomes were: inappropriateness of admission and “percentage of inappropriateness” for one hospitalization. A total number of 2196 clinical records were reviewed. The mean percentage of inappropriateness for hospitalization was 22%. The percentage of inappropriateness for the first 10 d of hospitalization peaked in correspondence of the fourth (42%). The logistic regression model on inappropriated admission reported that emergency admission was a protective factor (OR = 0.4) and to be hospitalized in wards with ≥30 beds risk factor (OR = 5.12). The second linear model on “percentage of inappropriateness” showed that inappropriated admission and wards with ≥30 beds increased the percentage (p < 0.001); whereas the admission in Teaching Hospitals was inversely associated (p < 0.001). The present study suggests that the percentage of inappropriate admission depends especially on the inappropriate admission and the large number of beds in obstetric wards. This probably indicates that management of big hospitals, which is very complex, needs improving the processes of support and coordination of health professionals. The OAEP tool seems to be an useful instrument for the decision-makers to monitor and manage the obstetric wards.

Osmotic indices and kidney concentrating activity: population-based data on correlates and prognostic power

Background Research data are limited on indices of osmotic equilibrium and of kidney concentrating activity (KCA). This study investigated correlates and prognostic power of these indices in a sample of the general population. Methods Urine osmolality (U-osm), plasma osmolality (P-osm), plasma creatinine and other variables were measured by the Gubbio Study for the 1988-92 exam (baseline). Plasma creatinine and other variables were re-measured in the 2001-07 exam (follow-up). KCA was assessed as the U-osm/P-osm ratio and kidney function as estimated glomerular filtration rate (eGFR). Results Baseline data were complete in 4220 adults, of whom 852 died before follow-up and 2795 participated in the follow-up. At baseline, the following independent cross-sectional associations were identified: female sex and higher urine flow with lower values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); obesity with higher values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); older age and lower eGFR with lower U-osm, lower U-osm/P-osm ratio and higher P-osm (P < 0.05); hypertension and smoking with lower U-osm and lower U-osm/P-osm ratio (P < 0.05) but not with P-osm. From baseline to follow-up, the annualized rate was 1.26% for mortality and -0.74 ± 0.76 mL/min × 1.73 m2 for eGFR change. Mortality was independently predicted by baseline U-osm and baseline U-osm/P-osm ratio (hazard ratio for one higher standard deviation was ≤0.91, 95% confidence interval was ≤0.97, P < 0.01), but not by baseline P-osm. The eGFR change was not independently predicted by baseline values of U-osm, P-osm and U-osm/P-osm ratio (P ≥ 0.4). Conclusions Sex, age, obesity, eGFR, urine flow, hypertension and smoking independently associated with U-osm and KCA. U-osm and KCA independently predicted mortality, but not kidney function change over time.

The Drug Prescription Process: A Network Medicine Approach

This section presents the definition of Network Science, and its fundamentals and attributes, the main mathematical aspects of the study of networks and the parameters, or quantitative indicators, used to study and analyze a network from a mathematical point of view. It introduces the concept of “Network Medicine,” the science that studies biological and medical phenomena from the point of view of networks.

General Practitioners Records Are Epidemiological Predictors of Comorbidities: An Analytical Cross-Sectional 10-Year Retrospective Study

Background. Comorbidity represents the co-occurrence of pathological conditions in the same individual, and presents with very complex patterns. In most cases, reference data for the study of various types of comorbidities linked to complex diseases are those of hospitalized patients. Such patients may likely require cure due to acute conditions. We consider the emerging role of EHR (Electronic Healthcare Records), and study comorbidity patterns in a general population, focusing on diabetic and non-diabetic patients. Methods. We propose a cross-sectional 10-year retrospective study of 14,958 patients and 1,728,736 prescriptions obtained from family doctors, and thus refer to these data as General Practitioner Records (GPR). We then choose networks as the tools to analyze the diabetes comorbidity patterns, distinguished by both prescription type and main patient characteristics (age, gender). Results. As expected, comorbidity increases with patients’ age, and the network representations allow the assessment of associations between morbidity groups. The specific morbidities present in the diabetic population justify the higher comorbidity patterns observed in the target group compared to the non-diabetic population. Conclusions. GPR are usually combined with other data types in EHR studies, but we have shown that prescription data have value as standalone predictive tools, useful to anticipate trends observed at epidemiological level on large populations. This study is thus relevant to policy makers seeking inference tools for an efficient use of massive administrative database resources, and suggests a strategy for detecting comorbidities and investigating their evolution.