Effect of olive leaves feeding on phenolic composition and lipolytic volatile profile in goat milk.

The aim of this study was to evaluate phenolic composition, antioxidant potential, and lipolytic events in raw milk obtained from goat fed a dietary supplementation with olive leaves (OL), a by-product of the olive oil production chain. For this purpose, 30 Saanen goats were randomly allocated into 2 groups of 15 goats each: the control group received a standard diet that was prepared by taking into account the nutritional needs of lactating goats, whereas the experimental group (EG) was fed with an OL-supplemented diet (10% on a dry matter basis). At the end of the 30 d of the trial, the individual milk samples were collected and immediately analyzed for total phenolic content and antioxidant activity (AOA). Subsequently, the individual phenolic compounds have been identified and quantified through an ultra-high-performance liquid chromatography system and a characterization of free fatty acids released in milk has been performed. The results showed a positive effect of dietary OL supplementation in improving total phenolic content and AOA; furthermore, 19 phenolic compounds, including phenolic acids, flavonoids, simple phenols, and secoiridoids, have been identified in EG milk. In addition to this, a reduced accumulation of free fatty acids has been found in EG milk, and this finding leads us to hypothesize an inhibitory action of the identified phenolic compounds toward the enzymes responsible for lipolytic events. The use of the molecular docking approach verified the interactions, defining a fairly interesting framework for cinnamic acid, which should be able to noncovalently bind these enzymes, interfering with the recruitment of the substrate and therefore, slowing down their hydrolytic activity. In any case, this information will be subjected to in vitro evaluations for an accurate characterization of the biochemical mechanisms that can be established in milk naturally enriched with bioactive compounds.

Metagenomic and volatile profiles of ripened cheese obtained from dairy ewes fed a dietary hemp seed supplementation.

Chemical and organoleptic properties of dairy products largely depend on the action of microorganisms that tend to be selected in cheese during ripening in response to the availability of specific substrates. The aim of this work was to evaluate the effects of a diet enriched with hemp seeds on the microbiota composition of fresh and ripened cheese produced from milk of lactating ewes. Thirty-two half-bred ewes were involved in the study, in which half (control group) received a standard diet, and the other half (experimental group) took a diet enriched with 5% hemp seeds (on a DM basis) for 35 d. The dietary supplementation significantly increased the lactose in milk, but no variations in total fat, proteins, caseins, and urea were observed. Likewise, no changes in total fat, proteins, or ash were detected in the derived cheeses. The metagenomic approach was used to characterize the microbiota of raw milk and cheese. The phyla Proteobacteria and Firmicutes were in equally high abundance in both control and experimental raw milk samples, whereas Bacteroidetes was less abundant. The scenario changed when considering the dairy products. In all cheese samples, Firmicutes was clearly predominant, with Streptococcaceae being the most abundant family in the experimental group. The reduction of taxa observed during ripening was in accordance with the increment (relative abundance) of the starter culture Lactococcus lactis and Streptococcus thermophilus, which together dominate the microbial community. The analysis of the volatile profile in ripened cheeses led to the identification of 3 major classes of compounds: free fatty acids, ketones, and aldehydes, which indicate a prevalence of lipolysis compared with the other biochemical mechanisms that characterize the cheese ripening.

Whole-transcriptome profiling of sheep fed with a high iodine-supplemented diet.

Iodine (I) is a micronutrient that mammals need for proper functionality of thyroid gland since it is the main component of thyroid hormones. Besides studies that have investigated the role of I in livestock nutrition, it is also important to know the transcriptomics changes in small ruminants following I supplementation. Therefore, the aim of this study was to investigate the effects of I on the whole blood transcriptome in sheep. Fifteen lactating cross-bred ewes (3 to 4-year-old, 55 to 65 kg BW) at their late lactation period were enrolled in this study. At the beginning, all the animals had a 2-week acclimation period where they were fed with a basal diet which includes an adequate level of I (2 mg I/animal per day) in the form of calcium iodate (CaI2O6). Then, the ewes were randomly divided into two groups and fed in individual troughs: the control group (n = 5) was maintained on basal diet and the experimental group (I, n = 10) was fed for 40 days with a diet containing a high I supplementation (equivalent to 30 mg I/animal per day), in the form of potassium iodide. Whole blood and milk were collected individually at the beginning (T0) and after the 40 days of supplementation (T40). Iodine quantification was assessed in serum and milk sample. Microarray gene expression analysis was performed on whole blood and, filtering data using a fold change >2 with an adjusted P < 0.05, we identified 250 differentially expressed genes (DEGs) in the I group (T40 v. T0). Looking for biological processes associated with our DEGs, we found significant association with cell growth regulation. Thus, our study unveils the role of I supplementation on gene expression in sheep improving the knowledge about micronutrients in animal nutrition.

Short communication: Compositional characteristics and aromatic profile of caciotta cheese obtained from Friesian cows fed with a dietary supplementation of dried grape pomace.

The aim of the present work was to explore the chemical-sensorial characteristics and aromatic profile of caciotta cheese obtained from Friesian cows fed a diet enriched with grape pomace obtained from red grape (Vitis vinifera L.). Dietary enrichment with grape pomace influenced the production of caciotta cheeses in interesting ways from a compositional point of view, as cheese samples were rich in polyphenols, giving a high antioxidant potential. From a biochemical standpoint, we noted a slight decrease of proteolysis during ripening, whereas, according to the analysis of volatile compounds, lipolysis was the most relevant phenomenon in samples. The presence of bioactive compounds also modified the fatty acid profile of milk and cheese, leading to an increase in concentration of linoleic, vaccenic, and rumenic acids. No significant variations were found in the sensory profile. These results showed the potential of dietary grape pomace intake to influence the chemical-nutritional and nutraceutical properties of cow milk and cheeses, whose introduction to the market could be attractive to consumers, providing interesting implications for the dairy industry. Finally, our results identified of a valid use of an agro-industrial by-product, grape pomace, whose disposal generally presents economic and environmental problems.

Microemulsion containing triamcinolone acetonide for buccal administration.

The aim of the present work was to investigate the potential of microemulsions for the buccal administration of triamcinolone acetonide. Microemulsions were developed by the construction of pseudoternary phase diagrams, using the aqueous titration method. Among all microemulsions prepared and tested for stability, three were selected and submitted to characterization and in vitro permeation/retention experiments, using pig esophageal epithelium, an accepted model of the buccal mucosa. Furthermore, one microemulsion was added of excipients (stearylamine, CTAB and chitosan) able to alter the charge of droplets. The results obtained show that the permeation of triamcinolone acetonide across pig esophageal epithelium was not influenced by the droplet size nor by the composition, but only by the presence of chitosan, polysaccharide able to increase the transport across mono and stratified epithelia. The determination of the permeation parameters allowed us to show that chitosan acts on the diffusion parameter across the tissue and not on the partitioning parameter; for the same reason the tissue retention of triamcinolone acetonide was not modified. Triamcinolone flux (2.6 µg cm-2 h-1) was too low to make systemic administration feasible (dose required 2.5 to 60 mg/day). The amount of triamcinolone acetonide recovered in the mucosa after only 10 min. of microemulsion application was much higher than after overnight application of the commercial paste Omicilon® A. This suggests that triamcinolone acetonide microemulsions can be an interesting alternative to the commercial formulation to treat diseases of the buccal mucosa. Owing to the fast uptake by the tissue, the formulation can be used as a mouthwash.

Ultra-low background and environmental measurements at Laboratorio Subterráneo de Canfranc (LSC).

To support the construction of experiments at the Laboratorio Subterráneo de Canfranc (LSC) in Spain, an Ultra-Low Background Service (ULBS) and a Copper Electroforming Service (CES) were created. The measurement technique employed at the ULBS is gamma spectroscopy with high purity germanium (HPGe) detectors. A new anti-radon system is being implemented. The main goal of CES is to obtain high-purity copper pieces. A new electroforming set-up inside LSC underground clean room is planned. Radon and environmental measurements at the LSC are presented. The ULBS and CES are reviewed.

Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism differentially predicts hippocampal function in medication-free patients with schizophrenia.

A Val(66)Met single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val(66)Met SNP and [(15)O]H(2)O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy participants, resulting in a significant diagnosis-by-genotype interaction. Exploratory analyses of interregional resting rCBF covariation revealed a specific and significant diagnosis-by-genotype interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype interaction was also found for working memory-related hippocampal rCBF change, which was uniquely attenuated in Met allele-carrying patients. Thus, both task-independent and task-dependent hippocampal neurophysiology accommodates a Met allelic background differently in patients with schizophrenia than in control subjects. Potentially consistent with the hypothesis that cellular sequelae of the BDNF Val(66)Met SNP interface with aspects of schizophrenic hippocampal and frontotemporal dysfunction, these results warrant future investigation to understand the contributions of unique patient trait or state variables to these robust interactions.

Prenatal risk factors for intraventricular hemorrhage, neonatal death and impaired psychomotor development in very low birth weight infants.

AIM: The aim of this study was to determine the relationship between preterm risk factors and neonatal death, cerebral hemorrhage and psychomotor development in very low birth weight infants. METHODS: A retrospective analysis based on a multivariate logistic regression model was conducted on 253 VLBW infants. Cerebral hemorrhage was assessed by cerebral ultrasound screening within 24 hours of life, psychomotor development by Bailey Psychomotor and Development Index test. RESULTS: Pre-eclampsia and elective cesarean section (CS) are statistically protective factors in the prevention of cerebral hemorrhage; gestational age is a protective factor for neonatal death; whereas, multiple pregnancy, symmetrically small for gestational-age infants, asphyxia at birth, altered cardiotocography, and cerebral hemorrhage are risk factors for neonatal death; emergency CS and gestational age are protective factors for problems in psychomotor development. The number of fetuses and cerebral hemorrhage are risk factors for impaired psychomotor development at 2 years of age. CONCLUSION: The great number of obstetrical variables related to neonatal outcome makes it difficult to identify the really important steps, in obstetric management, to prevent long term sequelae. The main risk factors related to psychomotor development still remain gestational age and multiple pregnancy.

Postmenopausal hormone therapy and mammographic breast density.

OBJECTIVE: The aim of this study was to evaluate the effects of different types of hormone replacement therapy (HRT) on mammographic density. MATERIALS AND METHODS: In a prospective 1-year study, 103 postmenopausal women were randomized to receive tibolone 2.5 mg/die, continuous conjugated equine estrogens 0.625 mg/die plus medroxyprogesterone acetate (MPA) 5mg/die or placebo. Mammograms were performed at baseline and after 12 months of treatment. Mammographic density was quantified according to the Wolfe classification. RESULTS: After 12 months of HRT 16 of the 35 patients (45.1%) receiving continuous combined hormonal therapy showed an increase of breast density change in the Wolfe classification. After treatment with tibolone, an up grading in breast density, according to Wolfe's classification, was found in 2 of the 43 patients (2.3%). No changes were recorded in the 25 patients of the control group. The difference between the group treated with continuous combined hormonal therapy and the control group was highly significant (p<0.001). The difference in breast density between patients in treatment with tibolone and the control group was not statistically significant (p=0.34). DISCUSSION: Continuous combination HRT may be more commonly associated with an increase of mammography density than tibolone treatment.

[Job satisfaction, burnout and stress amongst nursing staff: a survey in two hospitals in Rome]. / Soddisfazione lavorativa, burnout e stress del personale infermieristico: indagine in due ospedali di Roma.

The job satisfaction and psychological well-being of health care workers may significantly influence the quality of care they provide. The aim of this study was to assess burnout and psychiatric disorders, such as anxiety and depression, as well as evaluate job satisfaction among nurses working at the IDI-Sanità in Rome. Nurses (n = 545) were invited to answer an anonymous, self-administered questionnaire, which consisted of the Maslach Burnout Inventory (MBI), the General Health Questionnaire (GHQ-12), and a validated questionnaire to examine job satisfaction. Descriptive analyses and multiple logistic regression analysis were performed. The section designed to evaluate job satisfaction was specifically examined by means of principal component factor analysis. Two hundred and forty-two nurses answered the questionnaire (response rate: 44%). Emotional exhaustion was observed in 38% of respondents. No significant difference was detected between mean values ( standard deviation) at each of the three MBI subscales and Italian normative data. About 33% of respondents showed a GHQ-12 score typical for disorders such as anxiety or depression. High levels of job satisfaction were found to be associated to a lower likelihood both of emotional exhaustion at MBI and psychiatric morbidity at GHQ-12. Factor analysis on items investigating job satisfaction identified 4 factors that globally accounted for 61% of the total variance. The factors obtained could represent possible targets for action aimed at improving nurse satisfaction.

[Premature ovarian failure in patients affected by oncohematological disease]. / L'insufficienza ovarica prematura dopo chemioterapia in pazienti con neoplasie ematologiche.

AIM: Premature ovarian failure (POF) can be considered a consequence of chemotherapy performed in patients affected by oncohematological disease. The aim of this study was to evaluate the administration of GnRh analogs (aGnRh) to prevent gonadal toxicity associated with cancer treatment. METHODS: From April 1996 to May 2002 a total of 49 fertile women affected by oncohematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia) and treated with chemotherapy were evaluated. Ovarian function was studied through a 40.7 month observation period, after chemotherapy, in 3 different groups: women treated with aGnRh, oral contraceptives treatment and no preventive-treatment. The differences in these groups as to menstrual cycle, blood ovarian hormones, age at diagnosis, type and dosage of chemotherapy administered were evaluated. Statistical analysis was performed by chi2 test with Yates correction and Fisher test. RESULTS: All patients treated with aGnRh and chemotherapy achieved a good ovarian function. A normal ovarian function was also obtained in 75% of patients treated with oral contraceptives and only in 59.3% of women with no preventive treatment. Significant difference was found comparing aGnRh group with no preventive-treatment group (P<0.05). No significant differences were found between other groups. CONCLUSIONS: Use of GnRh analogs administered before beginning chemotherapy prevents from gonadal damage in all cases observed. Higher chemotherapy toxicity and older age at diagnosis time decrease ovarian function.

Burnout and job satisfaction comparing healthcare staff of a dermatological hospital and a general hospital.

BACKGROUND: Psychological distress among healthcare professionals can have negative effects on the well-being of the professionals and also on the quality of care they provide to patients. OBJECTIVES: To evaluate burnout and job satisfaction of dermatologists and nurses working with dermatological patients compared with physicians and nurses of other specialties. METHODS: A self-completed anonymous questionnaire was distributed to the personnel of two hospitals in Rome, Italy: a dermatological hospital (IDI) and a general hospital (GH), belonging to the same non-profit organization. Standardized instruments were used to assess burnout (Maslach Burnout Inventory) and job satisfaction. Multiple logistic regression was used to examine the association between burnout and working in dermatology vs. other specialties, job satisfaction, years of employment and respondents' sex and age. RESULTS: We distributed 929 questionnaires to clinical and non-clinical staff of IDI and 494 questionnaires to the GH staff (response rates: 53% at IDI and 50% at the GH). Among respondents there were 67 physicians and 59 nurses at IDI and 70 physicians and 148 nurses at the GH. Subsequent analyses refer only to this clinical subsample. Factor analysis showed that among physicians and nurses the two main factors explaining job satisfaction were respondents 'satisfaction with the management of their unit' and 'opportunities for personal growth'. Among nurses the likelihood of burnout decreased significantly with higher levels of job satisfaction [odds ratio (OR) = 0.78; 95% confidence interval (95% CI) 0.7-0.9] and working in dermatology compared with other specialties (OR = 0.46; 95% CI 0.2-0.9). Among physicians a lower likelihood of burnout was associated with job satisfaction (OR = 0.66; 95% CI 0.5-0.8) and older age (OR = 0.28; 95% CI 0.1-0.8). CONCLUSIONS: Among both physicians and nurses, job satisfaction was associated with a lower likelihood of burnout, independently of clinical specialty and other factors. Burnout was similar for dermatologists and other specialists. Nurses of the GH compared with those working in dermatology had a higher probability of burnout and were significantly less satisfied with the management of their units and with opportunities for personal growth.

Genetic thrombophilias and uterine artery Doppler velocimetry and preeclampsia.

OBJECTIVE: The aim of this study was to evaluate the correlation between genetic thrombophilic mutations, uterine artery Doppler at 24 weeks of gestation and preeclampsia. METHODS: In a case control study we performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 20 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the factor V Leiden was 17.4% in the women with preeclampsia and abnormal artery Doppler compared with 3.12% in the patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of prothrombin gene was 1.5 vs. 4.3% between women with normal pregnancies and with preeclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among the patients with preeclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic gene variants were found in women with preeclampsia and normal uterine artery Doppler. CONCLUSION: We demonstrated the important association between factor V Leiden mutation, abnormal uterine Doppler at 24 weeks and preeclampsia in our population.

[Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase]. / Screening per la pre-eclampsia in pazienti a basso rischio alla ventiquattresima settimana: flussimetria delle arterie uterine e varianti geniche del fattore V, della protrombina e della metilentetraidrofolato reduttasi.

AIM: Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. The aim of this study was to evaluate the clinical usefulness of screening of genetic thrombophilic mutations and uterine artery Doppler flow velocimetry at 24 weeks of gestation in the prediction of pre-eclampsia in low risk pregnant women. METHODS: We performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 24 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the Leiden FV was 17.4% in women with pre-eclampsia and abnormal artery Doppler flow velocimetry compared with 3.12% in patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of PT gene was 1.5% vs 4.3% between women with normal pregnancies and with pre-eclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among patients with pre-eclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic genes variants were found in women with pre-eclampsia and normal uterine artery Doppler flow velocimetry. CONCLUSION: We demonstrated the important association between FV Leiden mutation, abnormal uterine artery Doppler flow velocimetry at 24 weeks and pre-eclampsia in our low-risk population.

Epidemiology of essential hypertension: the role of genetic polymorphism.

Over the past 20 years, the interest of the scientific community was increasingly placed in the field of genetic epidemiology and molecular genetics of blood pressure control. This paper explores references related to essential hypertension, gene and genetic epidemiology indexed in the MedLine health science database during the period 1980-2001. A systematic literature search was performed using selected keywords, such as 'genetic', 'genome' or a combination of words. We considered the study heading and evaluated the time profile of published articles. A total number of 3116 publications was collected and analyzed. Allelic distribution for the most studied polymorphisms of the renin-angiotensin system in different world populations was reviewed and reported together with a detection of their frequency in Italy: essential hypertensive patients (n = 90), healthy unrelated subjects (n = 300). Molecular variants at angiotensinogen (M and T), angiotensin II type 1 receptor (A and C) and angiotensin-converting enzyme (D and I) genes were analyzed by amplified fragment length polymorphism. A significant association was detected by chi2 analysis for angiotensinogen and angiotensin II-type I receptor allele distribution in hypertensive patients, in accordance with previous reports. Genetic data and methods are contributing more and more to epidemiological studies of complex diseases, and their application is influenced by information availability and Genome Project results.

CCR5 and CCR2 gene polymorphisms in hypertensive patients.

Essential hypertension is a complex trait under polygenic control. Evidences suggests immune system involvement during pathogenesis. CC-chemokine receptor (CCR)5 and CCR2 are characterised by gene polymorphism. Variant alleles are derived from a deletion in the CCR5 gene (CCR5delta32) and a substitution mutation at the CCR2 locus (CCR264I). CCR polymorphic forms have been studied extensively as invasion cofactors for HIV-1, but they have also been implicated in immuno-related disorders. Here, we evaluate the allelic distribution of CCR5 and CCR2 genes in essential hypertension in a case-control study. Genotype frequency in a group of essential hypertensive patients (stage I-II; n=120) and a group of unrelated, healthy Caucasian subjects (n=340) is compared. CCR gene polymorphism is analysed by polymerase chain reaction and restriction enzyme digestion. A statistically significant difference was observed for CCR5 and CCR2 mutant alleles in essential hypertensive patients, compared with the controls (P=0.004 and P=0.003, respectively). CCR5delta32 and CCR264I alleles showed a 0.096 and 0.10 frequency among cases. To date, a role for the immune system in hypertension has not been clarified, nor has the predictive value of CCR polymorphisms.

[Induction of fetal lung maturation in the prevention of hyaline membrane disease: the connection with neonatal sepsis]. / Induzione della maturazione polmonare fetale nella profilassi della malattia da membrane ialine e sepsi neonatale.

BACKGROUND: The aim of this study was to evaluate the effect of antenatal maternal corticosteroid treatment on the frequency of neonatal outcomes and perinatal infectious morbidity among singleton pregnancies complicated by preterm delivery. METHODS: A nonrandomized analysis was performed on 189 neonates of 24-34 weeks' gestation who were born at the Department of Obstetrics and Gynecology, University of Udine, between January 2000 to December 2001. The neonates were subdivided into 3 groups: 1) 143 neonates received 2 doses of corticosteroids in a 24-hour interval and repeated after 10 days; 2) 26 neonates received 2 doses; 3) 20 neonates did not receive any treatment. Data were analysed with the Fisher exact test. p<0.05 was considered significant. RESULTS: The incidence of respiratory distress syndrome (RDS), neonatal mortality and intraventricular hemorrhage was respectively 43.4%, 3.2 % and 6.3 %. The rate of early-onset neonatal sepsis was 4.9% in the 1st group, 3.9% in the 2nd group and 5% in the 3rd group. There were no significant differences in the early-onset neonatal sepsis and the antenatal corticosteroids treatment. CONCLUSIONS: The single or the multiple courses of antenatal steroids did not apparently increase neonatal sepsis in patients with preterm delivery.

AGT and AT1R gene polymorphism in hypertensive heart disease.

Left ventricular hypertrophy in patients with hypertension is a main clinical prognostic entity The aim of this study was to evaluate the association between mutations at genes of the renin-angiotensin system (RAS) and the development of left ventricular hypertrophy. Genetic polymorphism in angiotensinogen (AGT) and angiotensin Il-type 1 receptor (AT1R) genes was examined in a group of well-selected essential hypertensive caucasians with left ventricular involvement (n = 40) and a group of healthy unrelated caucasians (n = 150). Cardiac morphology and function were assessed by M-mode echocardiography. Molecular variants were analysed by amplified fragment length polymorphism. We observed a statistically significant difference both for AGT and AT1R genotype distribution in patients with left ventricular hypertrophy compared with controls (p<0.05). A 0.49 and 0.225 frequency was detected among cases for T and C mutant alleles at AGT and AT1R genes. Mutations in RAS genes are involved in the pathophysiology of target-organ damage in essential hypertension. Evaluation of molecular factors conferring a risk of developing heart involvement may lead to better identification of patient subgroups and more effective control of the clinical course.