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.

Development of musculoskeletal models for the design and the pre-clinical validation of hip resurfacing prosthesis

Background. The surgical treatment of dysfunctional hips is a severe condition for the patient and a costly therapy for the public health. Hip resurfacing techniques seem to hold the promise of various advantages over traditional THR, with particular attention to young and active patients. Although the lesson provided in the past by many branches of engineering is that success in designing competitive products can be achieved only by predicting the possible scenario of failure, to date the understanding of the implant quality is poorly pre-clinically addressed. Thus revision is the only delayed and reliable end point for assessment. The aim of the present work was to model the musculoskeletal system so as to develop a protocol for predicting failure of hip resurfacing prosthesis. Methods. Preliminary studies validated the technique for the generation of subject specific finite element (FE) models of long bones from Computed Thomography data. The proposed protocol consisted in the numerical analysis of the prosthesis biomechanics by deterministic and statistic studies so as to assess the risk of biomechanical failure on the different operative conditions the implant might face in a population of interest during various activities of daily living. Physiological conditions were defined including the variability of the anatomy, bone densitometry, surgery uncertainties and published boundary conditions at the hip. The protocol was tested by analysing a successful design on the market and a new prototype of a resurfacing prosthesis. Results. The intrinsic accuracy of models on bone stress predictions (RMSE < 10%) was aligned to the current state of the art in this field. The accuracy of prediction on the bone-prosthesis contact mechanics was also excellent (< 0.001 mm). The sensitivity of models prediction to uncertainties on modelling parameter was found below 8.4%. The analysis of the successful design resulted in a very good agreement with published retrospective studies. The geometry optimisation of the new prototype lead to a final design with a low risk of failure. The statistical analysis confirmed the minimal risk of the optimised design over the entire population of interest. The performances of the optimised design showed a significant improvement with respect to the first prototype (+35%). Limitations. On the authors opinion the major limitation of this study is on boundary conditions. The muscular forces and the hip joint reaction were derived from the few data available in the literature, which can be considered significant but hardly representative of the entire variability of boundary conditions the implant might face over the patients population. This moved the focus of the research on modelling the musculoskeletal system; the ongoing activity is to develop subject-specific musculoskeletal models of the lower limb from medical images. Conclusions. The developed protocol was able to accurately predict known clinical outcomes when applied to a well-established device and, to support the design optimisation phase providing important information on critical characteristics of the patients when applied to a new prosthesis. The presented approach does have a relevant generality that would allow the extension of the protocol to a large set of orthopaedic scenarios with minor changes. Hence, a failure mode analysis criterion can be considered a suitable tool in developing new orthopaedic devices.

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.

Predictive Ability of NGAL as a Marker of Renal Damage: evaluation of Multiple Clinical Settings

Introduction. Neutrophil Gelatinase-Associated Lipocalin (NGAL) belongs to the family of lipocalins and it is produced by several cell types, including renal tubular epithelium. In the kidney its production increases during acute damage and this is reflected by the increase in serum and urine levels. In animal studies and clinical trials, NGAL was found to be a sensitive and specific indicator of acute kidney injury (AKI). Purpose. The aim of this work was to investigate, in a prospective manner, whether urine NGAL can be used as a marker in preeclampsia, kidney transplantation, VLBI and diabetic nephropathy. Materials and methods. The study involved 44 consecutive patients who received renal transplantation; 18 women affected by preeclampsia (PE); a total of 55 infants weighing ≤1500 g and 80 patients with Type 1 diabetes. Results. A positive correlation was found between urinary NGAL and 24 hours proteinuria within the PE group. The detection of higher uNGAL values in case of severe PE, even in absence of statistical significance, confirms that these women suffer from an initial renal damage. In our population of VLBW infants, we found a positive correlation of uNGAL values at birth with differences in sCreat and eGFR values from birth to day 21, but no correlation was found between uNGAL values at birth and sCreat and eGFR at day 7. systolic an diastolic blood pressure decreased with increasing levels of uNGAL. The patients with uNGAL <25 ng/ml had significantly higher levels of systolic blood pressure compared with the patients with uNGAL >50 ng/ml ( p<0.005). Our results indicate the ability of NGAL to predict the delay in functional recovery of the graft. Conclusions. In acute renal pathology, urinary NGAL confirms to be a valuable predictive marker of the progress and status of acute injury.

Determinants of cesarean delivery, a population-based study in the Emilia Romagna Region

Cesarean Delivery (CD) rates are rising in many parts of the world. In order to define strategies to reduce them, it is important to explore the role of clinical and organizational factors. This thesis has the objective to describe the contemporary CD practice and study clinical and organizational variables as determinants of CD in all women who gave birth between 2005 and June 2010 in the Emilia Romagna region (Italy). All hospital discharge abstracts of women who delivered between 2005 and mid 2010 in the region were selected and linked with birth certificates. In addition to descriptive statistics, in order to study the role of clinical and organizational variables (teaching or non-teaching hospital, birth volumes, time and day of delivery) multilevel Poisson regression models and a classification tree were used. A substantial inter-hospital variability in CD rate was found, and this was only partially explained by the considered variables. The most important risk factors of CD were: previous CD (RR 4,95; 95%CI: 4,85-5,05), cord prolapse (RR 3,51; 95% CI:2,96-4,16), and malposition/malpresentation (RR 2,72; 95%CI: 2,66-2,77). Delivery between 7 pm and 7 am and during non working days protect against CD in all subgroups including those with a small number of elective CDs while delivery at a teaching hospital and birth volumes were not statistically significant risk factors. The classification tree shows that previous CD and malposition/malpresentation are the most important variables discriminating between high and low risk of CD. These results indicate that other not considered factors might explain CD variability and do not provide clear evidence that small hospitals have a poor performance in terms of CD rate. Some strategies to reduce CD could be found by focusing on the differences in delivery practice between day and night and between working and no-working day deliveries.

Pre-clinical and clinical development of leukemia stem cell inhibitors in acute leukemias

In Leukemias, recent developments have demonstrated that the Hedgehog pathway plays a key-role in the peculiar ability of self renewal of leukemia stem cells. The aim of this research activity was to investigate, through a first in man, Phase I, open label, clinical trial, the role and the impact, mainly in terms of safety profile, adverse events and pharmacokinetics, of a Sonic Hedgehog inhibitor compound on a population of heavely pretreated patients affected by AML, CML, MF, or MDS, resistant or refractory to standard chemotherapy. Thirty-five patients have been enrolled. The drug was administered orally, in 28 days cycles, without rest periods. The compound showed a good safety profile. The half life was of 17-35 hours, justifying the daily administration. Significant signs of activity, in terms of reduction of bone marrow blast cell amount were seen in most of the patients enrolled. Interestingly, correlative biological studies demonstrated that, comparing the gene expression profyiling signature of separated CD34+ cells before and after one cycle of treatment, the most variably expressed genes were involved in the Hh pathway. Moreover, we observed that many genes involved in MDR (multidrug resistance)were significantly down regulated after treatment. These data might lead to future clinical trials based on combinatory approaches, including, for instance, Hh inhibitors and conventional chemotherapy.

Adulthood with Turner Syndrome: Quality of life, psychosocial adjustment and clinical management in 70 Italian women

Abstract Background: Turner syndrome (TS) is a chromosomal abnormality (total or partial absence of one of the sexual chromosomes in some or all cells of the body), which affects approximately 1:2000 female. Principal characteristics are short stature and gonadal disgenesis. Clinical management consist of Growth Hormone (GH) treatment and oestrogen replacement therapy (HRT), to induce development of secondary characteristics and to avoid the sequelae of oestrogen deficiency. Aim of the study: To assess clinical management, quality of life (QoL) and general psychosocial adjustment of women with TS. Population: 70 adult Caucasian females with TS (mean age: 27.8, ± 7.6; range 18-48 y.). Setting: Specialist service for Rare Disease care, University Hospital. Methods: Subjects were required to fill in questionnaires collecting ASR, WHOQOL, and 8 open questions. Data were compared with those of the Italian population or to those collected in a comparison group (70 healthy females, mean age: 27.9, ±7.3, range 21-48 y.). Results: Women with TS are educated as well as the Italian Population, but they have a less successful professional life. They show good QoL in general, but they appeared less satisfied in social area. They had statistically higher scores than the comparison group for depression, anxiety and withdrawal. Are less involved in a love relationship. Diagnosis communication was mostly performed by doctors or parents, satisfaction was higher when information was given by parents. Main preoccupation about TS are infertility, feeling of being different and future health problem. Conclusions: Italian people with TS were generally well adapted and have a good QoL, but lived more often with parents and show impaired sentimental and sexual life. They have higher degree of psychological distress compared to a comparison group. Psychological intervention should firstly address parents in order to encourage an open communication on diagnosis issues and on sexual education.