Well-being, distress and health status in a population of adolescent students

The present work explores the psychosocial issues emerging from a large cross-sectional study aimed to assess the prevalence, clinical manifestations, and psychosocial correlates of hyperandrogenism in a population of Italian high school students. Participants were 1804 adolescents, aged between 15 and 19 years, who volunteered to fill in a package of self-report questionnaires (including the Psychosocial Index, the Symptom Questionnaire and Ryff’s Psychological Well-Being scales for the assessment of psychological aspects) and undergo a comprehensive physical examination. Significant gender differences were found with regard to psychological distress, with females reporting higher scores compared with males, but not on well-being dimensions. The relationships of well-being to distress were found to be complex. Although inversely associated, well-being and ill-being appeared to be distinct domains of mental functioning. The evaluation of the moderating effects of well-being in the association between stress and psychological distress indicated that well-being may act as a protective factor, contributing to less pronounced psychological distress as stress levels increased. Higher rates of somatic complaints were found among current smokers. However, substance use (i.e., smoking and drug use) was also found to be positively associated with some well-being dimensions. A considerable number of participants were found to present with disordered eating symptoms, particularly females, and associated higher stress levels and lower quality of life. Sport activities were found to favourably affect psychological health. As to clinical signs of hyperandrogenism, a significant impairment in psychosocial functioning was found among females, whereas no effects on psychological measures could be detected among males. Subgroups of adolescents with distinct clinical and psychological characteristics could be identified by means of cluster analysis. The present study provides new insights into better understanding of the complex relationships between well-being, distress and health status in the adolescent population, with important clinical implications.

Automatic risk evaluation in elderly patients based on Autonomic Nervous System assessment

Dysfunction of Autonomic Nervous System (ANS) is a typical feature of chronic heart failure and other cardiovascular disease. As a simple non-invasive technology, heart rate variability (HRV) analysis provides reliable information on autonomic modulation of heart rate. The aim of this thesis was to research and develop automatic methods based on ANS assessment for evaluation of risk in cardiac patients. Several features selection and machine learning algorithms have been combined to achieve the goals. Automatic assessment of disease severity in Congestive Heart Failure (CHF) patients: a completely automatic method, based on long-term HRV was proposed in order to automatically assess the severity of CHF, achieving a sensitivity rate of 93% and a specificity rate of 64% in discriminating severe versus mild patients. Automatic identification of hypertensive patients at high risk of vascular events: a completely automatic system was proposed in order to identify hypertensive patients at higher risk to develop vascular events in the 12 months following the electrocardiographic recordings, achieving a sensitivity rate of 71% and a specificity rate of 86% in identifying high-risk subjects among hypertensive patients. Automatic identification of hypertensive patients with history of fall: it was explored whether an automatic identification of fallers among hypertensive patients based on HRV was feasible. The results obtained in this thesis could have implications both in clinical practice and in clinical research. The system has been designed and developed in order to be clinically feasible. Moreover, since 5-minute ECG recording is inexpensive, easy to assess, and non-invasive, future research will focus on the clinical applicability of the system as a screening tool in non-specialized ambulatories, in order to identify high-risk patients to be shortlisted for more complex investigations.

Simkania negevensis: clinical and laboratory studies in the population of hemodialized and kidney transplanted patients.

Simkania negevensis is a bacterium belonging to the order Chlamydiales but with certain biological characteristics different from those of chlamydia, according to which it was classified in the family Simkaniaceae. It is widespread in the environment, due to its ability to survive in amoebae also in phase cystic, for which it was hypothesized a possible transmission after contact with water in which they are present amoebae. So far it is known its role in diseases of the lower respiratory tract, such as childhood bronchiolitis and pneumonia in adults of the community, following its transmission through infected aerosols. A recent American study showed, by PCR, a high prevalence of S. negevensis in patients with lung transplant than other transplant recipients, assuming an association between the presence of the bacterium in these patients, and transplant rejection, were more frequent in lung transplant recipients infected compared to uninfected. There are no data so far analyzed in Italy relative to the population of dialysis and kidney transplant recipients relative to simkania negevensis why this study was undertaken in order to start a specific location and evaluate the scientific implications. Because its ability to assume persistent forms of infection, which may lead to a prolonged inflammatory response, Simkania negevensis, similar to other persistent bacteria or viruses, may be ivolved in pathologic complication. Sn may be a factor in graft rejection in mmunesuppressed lung transplant recipients, and further studies are planned to explore the posible association of Sn infections with various in vivo pathologies.

Anatomical biomarkers of body composition in oncological population: application and development of artificial intelligences

In the Era of precision medicine and big medical data sharing, it is necessary to solve the work-flow of digital radiological big data in a productive and effective way. In particular, nowadays, it is possible to extract information “hidden” in digital images, in order to create diagnostic algorithms helping clinicians to set up more personalized therapies, which are in particular targets of modern oncological medicine. Digital images generated by the patient have a “texture” structure that is not visible but encrypted; it is “hidden” because it cannot be recognized by sight alone. Thanks to artificial intelligence, pre- and post-processing software and generation of mathematical calculation algorithms, we could perform a classification based on non-visible data contained in radiological images. Being able to calculate the volume of tissue body composition could lead to creating clasterized classes of patients inserted in standard morphological reference tables, based on human anatomy distinguished by gender and age, and maybe in future also by race. Furthermore, the branch of “morpho-radiology" is a useful modality to solve problems regarding personalized therapies, which is particularly needed in the oncological field. Actually oncological therapies are no longer based on generic drugs but on target personalized therapy. The lack of gender and age therapies table could be filled thanks to morpho-radiology data analysis application.

Nuove acquisizioni in termini di insufficienza mitralica: complicanze tromboemboliche dopo chirurgia della valvola mitrale: incidenza, predittori e implicazioni cliniche

Objectives: to define in patients undergoing surgery for mitral regurgitation (MR) the risk of thrombo-embolic complications, particularly ischemic stroke (IS) compared to that in the general population. Background: MR is frequent, occurs mostly in the elderly and guidelines recommend surgery in asymptomatic patients but IS risks are unknown. Methods: in 1344 patients (65±12 years) consecutively operated for MR (procedures: 897 valve repair, MRep; 447 valve replacement, 231 mechanical, MVRm; 216 biological, MVRb), thrombo-embolic complications particularly IS (diagnosed by a neurologist) during follow-up were assessed early (<30 days), mid-term (30-180 days) and long-term (180 days). Results: IS occurred in 130 patients and IS or transient ischemic attack in 201. IS rates were 1.9±0.4% and 2.7±0.5%, at 30 and 180 days and 8.1±0.8% at 5 years. IS rates were lowest after MRep vs. MVRb and MVRm (6.1±0.9, 8±2.1 and 16.1±2.7% at 5 years, p<0.001). Comparison to IS expected rates in the population showed high risk within 30 days of surgery (Risk-ratio 41[26-60], p<0.001 but p>0.10 between procedures) and moderate risk after 30 days (risk-ratio 1.7 overall, p<0.001; 1.3 for MRep, p=0.07; 0.98 for MVRb, p=0.95; 4.8 for MVRm, p<0.001). Beyond 180 days, IS risk declined further and was not different from the general population for MRep (1.2, p=0.30) and for MVRb (0.9, p=0.72). Risk of IS or transient ischemic attack was higher than the general population in all groups up to 180 days. The risk of bleeding beyond 30 days was lowest in MRep vs. MVRb and MVRm (7±1, 14±4 and 16±3% at 10 years, p<0.001). Conclusion: thrombo-embolic complications after MR surgery are both reason for concern and encouragement. IS risk is notable early, irrespective of the procedure performed, but long-term is not higher than in the general population after MRep and MVRb. Preference for MRep should be emphasized and trials aimed at preventing IS should be conducted to reduce the thrombo-embolic and hemorrhagic risk in patients undergoing surgery for MR.

Risk factors for postoperative delirium in the elderly

Background: Delirium is defined as an acute disorder of attention and cognition. Delirium is common in hospitalized elderly patient and is associated with increased morbidity, length of stay and patient care costs. Although Delirium can develop at any time during hospitalization, it typically presents early in the post-operative period (Post-Operative Delirium, POD) in the surgery context. The molecular mechanism and possible genetics basis of POD onset are not known, as well as all the risk factors are not completely defined. Our hypothesis is that genetic risk factor involving the inflammatory response could have possible effects on the immunoneuroendocrine system. Moreover, our previous data (inflamm-aging) suggest that aging is associated with an increase of inflammatory status, favouring age-related diseases such as neurodegenerative diseases, frailty, depression among other. Some pro-inflammatory or anti-inflammatory cytokines, seem to play a crucial role in increasing the inflammatory status and in the communication and regulation of immunoneuroendocrine system. Objective: this study evaluated the incidence of POD in elderly patients undergoing general surgery, clinical/physical and psychological risk factors of POD insurgency and investigated inflammatory and genetic risk factors. Moreover, this study evaluated the consequence of POD in terms of institutionalization, development of permanent cognitive dysfunction or dementia and mortality Methods: patients aged over 65 admitted for surgery at the Urgency Unit of S.Orsola-Malpighi Hospital were eligible for this case–control study. Risk factors significantly associated with POD in univariate analysis were entered into multivariate analysis to establish those independently associated with POD. Preoperative plasma level of 9 inflammatory markers were measured in 42 control subjects and 43 subjects who developed POD. Functional polymorphisms of IL-1 α , IL-2, IL-6, IL-8, IL-10 and TNF-alpha cytokine genes were determined in 176 control subjects and 27 POD subjects. Results: A total of 351 patients were enrolled in the study. The incidence of POD was 13•2 %. Independent variables associated with POD were: age, co-morbidity, preoperative cognitive impairment, glucose abnormalities. Median length of hospital stay was 21 days for patients with POD versus 8 days for control patients (P < 0•001). The hospital mortality rate was 19 and 8•4 % respectively (P = 0•021) and mortality rate after 1 year was also higher in POD (P= 0.0001). The baseline of IL-6 concentration was higher in POD patients than patients without POD, whereas IL-2 was lower in POD patients compared to patients without POD. In a multivariate analysis only IL-6 remained associated with POD. Moreover IL-6, IL-8 and IL-2 are associated with co-morbidity, intra-hospital mortality, compromised functional status and emergency admission. No significant differences in genotype distribution were found between POD subjects and controls for any SNP analyzed in this study. Conclusion: In this study we found older age, comorbidity, cognitive impairment, glucose abnormalities and baseline of IL-6 as independent risk factors for the development of POD. IL-6 could be proposed as marker of a trait that is associated with an increased risk of delirium; i.e. raised premorbid IL-6 level predict for the development of delirium.

Data management and data analysis in the large European projects GEHA (GEnetics of Healthy Aging) and NU-AGE (NUtrition and AGEing): a bioinformatic approach

The aging process is characterized by the progressive fitness decline experienced at all the levels of physiological organization, from single molecules up to the whole organism. Studies confirmed inflammaging, a chronic low-level inflammation, as a deeply intertwined partner of the aging process, which may provide the “common soil” upon which age-related diseases develop and flourish. Thus, albeit inflammation per se represents a physiological process, it can rapidly become detrimental if it goes out of control causing an excess of local and systemic inflammatory response, a striking risk factor for the elderly population. Developing interventions to counteract the establishment of this state is thus a top priority. Diet, among other factors, represents a good candidate to regulate inflammation. Building on top of this consideration, the EU project NU-AGE is now trying to assess if a Mediterranean diet, fortified for the elderly population needs, may help in modulating inflammaging. To do so, NU-AGE enrolled a total of 1250 subjects, half of which followed a 1-year long diet, and characterized them by mean of the most advanced –omics and non –omics analyses. The aim of this thesis was the development of a solid data management pipeline able to efficiently cope with the results of these assays, which are now flowing inside a centralized database, ready to be used to test the most disparate scientific hypotheses. At the same time, the work hereby described encompasses the data analysis of the GEHA project, which was focused on identifying the genetic determinants of longevity, with a particular focus on developing and applying a method for detecting epistatic interactions in human mtDNA. Eventually, in an effort to propel the adoption of NGS technologies in everyday pipeline, we developed a NGS variant calling pipeline devoted to solve all the sequencing-related issues of the mtDNA.