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Contains fulltext : 125353.pdf (Publisher’s version ) (Open Access) BACKGROUND: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of beta-cell function and metabolic control was examined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve beta-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 microg calcitriol per day or placebo (1:1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P

Acute lymphoblastic leukemia (ALL) is the most common subtype of leukemia in children. Although ALL and type 1 diabetes appear to be biologically unrelated, there are common threads in both epidemiology and etiology. Rising incidence rates of both ALL (1) and type 1 diabetes (2) observed over recent decades in many Western countries seem to support common etiological factors (3). In the current study, we report on diabetes-related autoantibodies (Abs) in a group of patients with ALL. Thirty-four consecutive children (19 males and 15 females, mean age 6.2 ± 4.6 years) were referred to our institution in 2004 for newly diagnosed ALL. Patients were tested for Abs to islet and thyroid antigens. After the initial investigation and treatment, 31/34 (91%) patients (3 died in the mean time) were followedup for 6 years to evaluate the evolution of the autoimmune markers and progression toward type 1 diabetes. Glutamic acid decarboxylase (GAD) Abs by direct …

The main objective of this study is to assess the course of peroneal mononeuropathy (PM). The study design includes Clinical and Prospective study. The setting involves neurophysiological Service. From November 2002 to January 2004, we enroled 69 consecutive patients and prospectively followed up 49 patients with multiple measurements. Comparison was made between follow-up and baseline values, and baseline factors were used to predict the PM evolution in multiple regression analysis. At follow-up, we observed a significant improvement of all clinical, neurophysiological and disability measurements, and physical aspects of quality of life (QoL). Greater muscle strength of tibialis anterior and higher conduction velocity of peroneal nerve at baseline were seen to be positive prognostic factors. A better evolution of mental aspects of QoL was observed in the subacute group and in younger patients, while a better physical evolution in QoL was observed in women. Rehabilitation is ambiguously associated with a better Deambulation Index but lower ratings in mental aspects of QoL. In conclusion, PM shows a positive spontaneous course and rehabilitation seems to help the recovery of deambulation. Further studies on the effects of conventional rehabilitation are needed.

Background A number of recent studies underline the importance of vitamin D in the pathogenesis of Type 1 diabetes (T1D). Aims The aim of this study was to investigate whether supplementation with the active form of vitamin D (calcitriol) in subjects with recent-onset T1D protects residual pancreatic β-cell function and improves glycaemic control (HbA1c and insulin requirement). Methods In this open-label randomized trial, 70 subjects with recent-onset T1D, mean age 13.6 years ± 7.6 sd were randomized to calcitriol (0.25 µg on alternate days) or nicotinamide (25 mg/kg daily) and followed up for 1 year. Intensive insulin therapy was implemented with three daily injections of regular insulin + NPH insulin at bedtime. Results No significant differences were observed between calcitriol and nicotinamide groups in respect of baseline/stimulated C-peptide or HbA1c 1 year after diagnosis, but the insulin dose at 3 and 6 months was significantly reduced in the calcitriol group. Conclusions At the dosage used, calcitriol has a modest effect on residual pancreatic β-cell function and only temporarily reduces the insulin dose.

The preservation of local landraces represents a crucial point in biodiversity maintenance and it necessarily starts from a qualitative and morphological characterization. The 'San Marzano' tomato (Solanum lycopersicum L.) is an elongated fruit cultivar particularly suitable for processing and represents one of the most significant horticultural products for the Italian food industry. Five 'San Marzano' landraces ('SM Bellizzi 1', 'SM Bellizzi 2', 'SM Bellizzi 3', 'SM Montoro Inferiore' and 'SM Sarno') characterized by different fruit shapes (pointed, round and hollow) were compared in terms of yield, nutritional and functional quality. The fruit dry matter percentage as well as the juice EC ranged from 4.94 to 7.10% and from 3.04 to 3.80 dS m-1, respectively, with the lowest values observed in 'SM Montoro Inferiore'. The highest total soluble solids content was recorded in both 'SM Montoro Inferiore' and 'SM Sarbo', followed by 'SM Bellizzi 1' and 'SM Bellizzi 3', whereas the lowest values were observed in both 'SM Bellizzi 2' and 'SM Bellizzi 3'. Among the three macronutrients analyzed K was the most abundant macro-mineral, followed by phosphorus and finally nitrate. 'SM Bellizzi 1' was richer in P and K compared to the rest of the landraces tested. The highest levels of hydrophilic and lipophilic antioxidant activities were recorded in 'SM Sarno' and 'SM Bellizzi 3', respectively. Our findings will contribute toward the documentation of nutritional and functional quality profiles of an important collection of niche products such as the SM tomato.

Salinization of agricultural land is an expanding phenomenon, which requires a multi-level strategy to counteract its deleterious effects on crop yield and quality. Plant biostimulants are increasingly used in agriculture with multiple purposes, including protection against abiotic stresses such as drought and salinity. The complex nature of plant biostimulants, however, makes it difficult to establish a cause&ndash, effect relationship between the composition of the commercial product and its expected effects. Here, we demonstrate that field applications of two algal derivatives (Rygex, R and Super Fifty, SU) cause a 26% reduction in shoot biomass and a remodulation of the root-to-shoot ratio under moderately saline irrigation (6.3 dS m&minus, 1). Moreover, plants treated with the two algal derivatives showed lower leaf water potential and improved water use efficiency under control conditions, suggesting an osmo-priming effect by these two products. These pre-adaptation responses increased tomato yield by 49% (R) and 70% (SU) regardless of the salinity level, with a remarkable reallocation of the biomass toward the fruits. Overall, our results suggest that the application of these two biostimulants can be useful in the open field to protect tomato plants from osmotic stress due to seasonal salinization, a phenomenon that typically occurs in arid and semi-arid environments.

// Chiara Autilio 1 , Carmela Paolillo 1 , Maria Michela Lavieri 2 , Krizia Pocino 1 , Elisa De Paolis 1 , Enrico Di Stasio 3 , Paolo Marchetti 4 , Cappellini Antonini Gian Carlo 6 and Ettore Capoluongo 1, 5, 7 1 Institute of Clinical Biochemistry, Laboratory of Clinical Molecular Diagnostics, Fondazione Policlinico “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy 2 Unit of Dermatology, “Cristo Re” Hospital, Rome, Italy 3 Laboratory of Clinical Biochemistry, Fondazione Policlinico “A. Gemelli”, Rome, Italy 4 Sant’Andrea Hospital, Rome, Italy 5 Laboratory of Advanced Molecular Diagnostics (DIMA), Istituto Dermopatico dell’Immacolata, Fondazione Luigi Maria Monti, IRCCS, Rome, Italy 6 Oncology Unit Immacolata Dermatological Institute (IDI), Rome, Italy 7 “Molipharma Srl” a Spinoff of Catholic University, Campobasso, Italy Correspondence to: Ettore Capoluongo, email: e.capoluongo@idi.it , ettoredomenico.capoluongo@unicatt.it Keywords: melanoma molecular biomarker, qRT-PCR, melanoma relapse, circulating tumor cells, PAX3 Received: June 17, 2017 Accepted: July 25, 2017 Published: August 11, 2017 ABSTRACT Objective: The aim of this study was to evaluate if our molecular algorithm, based on tumor circulating transcripts, may predict relapse risk in cutaneous malignant melanoma (CMM). Results: The multi-marker panel was able to differentiate patients with CMM from HC with high diagnostic sensitivity and specificity, especially for MITF-m and TGFB2 (91–100%) whose levels decreased during follow-up of recurrence-free patients, and remained stable in the case of relapse. PAX3d higher than 2.76 copies/μL emerged as a promising biomarker [specificity = 75–93% and negative predictive value = 75–98%] to stratify subjects at high risk of CMM recurrence independently of age, gender and AJCC staging [OD = 9.5(3.2–28.0), p < 0.001]. The survival analysis confirmed PAX3d performance in relapse prediction with significant differences in recurrence risk 12 months after the basal time-point ( p = 0.008). Materials and Methods: Peripheral blood was collected from 111 CMM patients and from 87 healthy controls (HC) randomly selected. Each specimen was examined by qRT-PCR analysis for the expression of 3 tumor-related transcripts (PAX3d, MITF-m and TGFB2) at diagnosis, and at the following 6 and 12 months during clinical monitoring. Conclusions: We demonstrated the usefulness of our molecular algorithm to indirectly detect circulating melanoma cells in blood, along with PAX3d capability to assess patients’ progression and relapse prediction.

In liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed.The aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure.Fifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients.The presence of the ACE I allele was associated with a higher HVPG value (18.7±6.4 vs 10.3±6.3mmHg; P.001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P.05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P.05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy.ACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease.

Objectives: To analyze a possible association between glutathione-S-transferase T1 (GSTM1) and/or glutathione-S-transferase M1 (GSTM1) polymorphisms and chronic or aggressive forms of periodontitis in a Caucasian ethnic group. Design and methods: Sixty-nine chronic, 14 aggressive periodontitis and 61 controls, deeply analyzed from a clinical point of view, were studied for their GSTM1 and GSTT1 polymorphisms by allelic specific PCR techniques. As a second control group, 64 blood donors were also included. Results: A significant association was found between GSTM1-null genotype and both chronic and aggressive periodontitis. The aggressive forms were associated with the double null GSTM1 and GSTT1 combination. These results were independent of the patients' age, gender, hygienic habits and smoke (evaluated as tobacco smoking yes/no, cigarettes/day and pack years) as confirmed by multivariate logistic regression analysis. Conclusions: The GSTM1-null variant is statistically associated with the two forms of periodontitis, while the aggressive one also presents a second null variant: GSTT1.

Patency of the ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) development represent severe affections for premature newborns, therefore the research of early markers for these two conditions is really important. The aim of this study is to analyze epithelial lining fluid (ELF) Neutrophil-gelatinase-associated lipocalin (NGAL) levels for prediction of lung injury or possible involvement of this molecule in PDA. Only scarce and contrasting results have previously been published in this field. In contrast, this molecule, included in a large macromolecular complex together with matrix metalloproteinase-9 (MMP-9), is considered an acceptable marker of infectious/inflammatory processes, cancer monitoring and induction of apoptotic pathway. NGAL was detected in 28 pre-term newborns by means of a commercially available kit in bronchoalveolar lavage fluid (BALF). The results have been corrected to ELF levels, by the urea method, to eliminate bias due to BALF collection. ELF NGAL levels were found significantly increased both in infants developing BPD or in those affected by PDA. By means of multivariate logistic regression analysis the significances were confirmed after adjusting for possible interfering variables such as gestational age and concomitant presence of both PDA and BPD. Our results stress the involvement of NGAL in the mechanisms leading to BPD and also suggest a possible association with PDA, which is often linked to prematurity and BPD development, probably due to the involvement of inflammatory and angiogenetic processes in both pathologies.

Summary Background Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. Objectives The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. Methods One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. Results All cases and controls were in Hardy–Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0·02) along with Breslow thickness (P = 0·001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. Conclusions Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.

Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O2 dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

Background Even though the gene encoding for IGF-I is considered of most importance amongst blood pressure-regulating genes in mouse models, little and discordant data are available in literature for what concerns a possible relationship between blood pressure and serum free IGF-I values in humans. In addition, no information is available on type 1 diabetes patients. Aim: Our aim is to analyze the relationship between systolic and diastolic blood pressure and serum free IGF-I and IGFBP-3 levels in subjects suffering from type 1 diabetes. Results: A highly significant inverse correlation was observed between serum free IGF-I levels and both systolic and diastolic blood pressure in subjects affected with type 1 diabetes. Similar but less significant relationships were observed for IGFBP-3, whose levels were also significantly and directly correlated with those of free IGF-I. The correlation between systolic and diastolic blood pressures with free IGF-I and between systolic blood pressure and IGFBP-3 levels were confirmed after adjusting for age, gender, age at diagnosis, disease duration, familial history, HBA1c, and amount of insulin administered by multivariate logistic regression analysis. A decrease in free IGF-I and IGFBP-3 levels, along with increases in blood pressure, significantly influenced the presence of diabetic complications, confirming how these molecules may be considered as severity markers for patients with type 1 diabetes as well as risk factors for altered pressure control linked diseases.

Objective.—The study explored the hypothesis that spontaneous nystagmus (Ny) in migraine patients can be triggered or modulated by painful trigeminal stimulation, providing evidence of a functional connection between vestibular and trigeminal systems. Background.—Vertigo attacks are reported by subjects with migraine or a familiar history of migraine, also independently of headache episodes. Idiopathic vertigo is three times more frequent in migraine patients than in controls. Vestibular investigations in migraine patients have consistently demonstrated spontaneous Ny both of central and peripheral origin. Design.—In the first phase of the study 10 outpatients experiencing migraine without aura (MO) and 10 healthy volunteers were submitted to the registration of spontaneous primary-position Ny in the dark by Ulmer's video-ocular-nystagmographic equipment. Two electrodes for electrical stimulation were applied on the supraorbital point of one side of the head and the intensity of stimulation corresponding to pain threshold was calculated. Spontaneous ocular movements were recorded for 5 minutes at baseline and after a sequence of five electric pulses (square waves of .5 Hz frequency and 50 μs duration, at pain threshold intensity). Nystagmographic responses were expressed as latency after stimulation, direction of the quick phase, and duration. The second phase of the study explored, with the same procedure, the effects on Ny of supraorbital versus median nerve stimulation in other 10 MO patients. Responses to stimulation were considered the appearance of de novo Ny after stimulation in subjects without baseline Ny, or the change of the frequency (at last a 50% variation) or of the direction of Ny after stimulation in subjects with baseline Ny. The latency and the duration of responses to stimulation were also calculated. Results.—In the first series supraorbital painful electric stimulation was able to modify or to evoke Ny in 8 of 10 migraineurs and in none of 10 volunteers (Fisher's exact test, P < .01). Both the baseline and the induced Ny were second degree, stationary persistent, with a linear slow phase and were suppressed by visual fixation. In the second series, supraorbital nerve stimulation was able to induce or modify Ny in all of 10 patients but only in 1 patient Ny was induced by median nerve stimulation. Characters of Ny were the same as previously described. Statistical comparison of the responses at the two sites of stimulation was significant (Fisher's exact test, P < .01). In those 7 patients who presented de novo Ny after stimulation it was possible to calculate Ny latency and duration. The mean latency was 25 s (SD: 16, range: 14 to 60). The mean duration was 120 s (SD: 94, range: 20 to 290). Conclusion.—The main result of our study is that in migraine patients painful trigeminal stimulation elicits de novo, or modifies pre-existing spontaneous Ny, generally increasing it. The finding was obtained after trigeminal stimulation, but not after median nerve stimulation. We suggest that painful trigeminal stimulation can induce an imbalance of the vestibular system in migraine patients and possibly explain their predisposition to vertigo. Our data require confirmation by other studies.