Neuroanatomy of the bipolar brain: from brain structure to treatment

In this thesis, I summarized results from researches done during my PhD course, organizing them in a brief introduction and five chapters. Specifically, the first chapter of this work is dedicated to the progress made during the past years in neuroimaging technologies and techniques, with a focus on structural Magnetic Resonance Imaging techniques and their employment into the neuropsychiatric research. The following three chapters are dedicated to the three studies, all developed though a specific research topic and directed to the understanding of the neural basis of Bipolar Disorder and its clinical implications

Parent\u2019s perception of children\u2019s fear: from FSSC-IT to FSSC-PP

Studies involving parents' reports about children's fears and multiple informant comparisons are less extended than investigations on children's self-reporting fear schedules. Starting with the Italian version of FSSC-R, the FSSC-IT, the main aims of this study were to adapt a schedule for parents' perception of their children's fear: the FSSC-Parent Perception. Its psychometric properties were examined in a large sample of parents (N = 2970) of children aged 8-10 years. Exploratory and confirmatory factorial structures were examined and compared with the Italian children's ones. Mother vs. father, children's gender and school age group effects were analyzed. The confirmatory factor analysis confirmed a four correlated factors solution model (Fear of Danger and Death; Fear of Injury and Animals; Fear of Failure and Criticism; Fear of the unknown and Phobic aspects). Some effects related to child gender, age group, mother vs. father, were found. The FSSC-PP properties supported its use by parents to assess their children's fears. A qualitative analysis of the top 10 fears most endorsed by parents will be presented and compared with children's fears. Clinical implications about the quality of parent-child relationships where discussed, comparing mothers and fathers, and parents' perception about daughters' and sons' most endorsed fears

Synthesis and characterization of Na‑P1 (GIS) zeolite using a kaolinitic rock

This work focuses on the hydrothermal synthesis of Na-P1 zeolite by using a kaolinite rock coming from Romana (Sassari, Italy). The kaolin is calcined at a temperature of 650 °C and then mixed with calculated quantities of NaOH. The synthesis runs are carried out at ambient pressure and at variable temperatures of 65 and 100 °C. For the first time compared to the past, the Na-P1 zeolite is synthesized without the use of additives and through a protocol that reduces both temperatures and synthesis times. The synthesis products are analysed by X-ray diffraction, high temperature X-ray diffraction, infrared spectroscopy, scanning electron microscopy and inductively coupled plasma optical emission spectrometry. The cell parameters are calculated using the Rietveld method. Density and specific surface area are also calculated. The absence of amorphous phases and impurities in synthetic powders is verified through quantitative phase analysis using the combined Rietveld and reference intensity ratio methods. The results make the experimental protocol very promising for an industrial transfer

Downregulation of NOX4 Expression by Roflumilast N-Oxide Reduces Markers of Fibrosis in Lung Fibroblasts

The phosphodiesterase 4 inhibitor roflumilast prevents bleomycin- (BLM-) induced lung fibrosis in animal models. However, its mechanism of action remains unknown. We investigated whether roflumilast N-oxide (RNO), the active metabolite of roflumilast, can modulate in vitro the oxidative effects of BLM on human lung fibroblasts (HLF). In addition, since BLM increases the production of F2-isoprostanes that have per se fibrogenic activity, the effect of RNO on oxidative stress and fibrogenesis induced by the F2-isoprostane 8-epi-PGF2α was investigated. HLF were preincubated either with the vehicle or with RNO and exposed to either BLM or 8-epi-PGF2α. Proliferation and collagen synthesis were assessed as [3H]-thymidine and [3H]-proline incorporation. Reactive oxygen species (ROS) and F2-isoprostanes were measured. NADPH oxidase 4 (NOX4) protein and mRNA were also evaluated. BLM increased both cell proliferation and collagen synthesis and enhanced ROS and F2-isoprostane production. These effects were significantly prevented by RNO. Also, RNO significantly reduced the increase in both NOX4 mRNA and protein, induced by BLM. Finally, 8-epi-PGF2α per se stimulated HLF proliferation, collagen synthesis, and NOX4 expression and ROS generation, and RNO prevented these effects. Thus, the antifibrotic effect of RNO observed in vivo may be related to its ability to mitigate ROS generation via downregulation of NOX4

The Increasing Challenge of Multidrug-Resistant Gram-Negative Bacilli: Results of a 5-Year Active Surveillance Program in a Neonatal Intensive Care Unit

Colonization and infection by multidrug-resistant gram-negative bacilli (MDR GNB) in neonatal intensive care units (NICUs) are increasingly reported.We conducted a 5-year prospective cohort surveillance study in a tertiary NICU of the hospital "Paolo Giaccone," Palermo, Italy. Our objectives were to describe incidence and trends of MDR GNB colonization and the characteristics of the most prevalent organisms and to identify the risk factors for colonization. Demographic, clinical, and microbiological data were prospectively collected. Active surveillance cultures (ASCs) were obtained weekly. Clusters of colonization by extended spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae were analyzed by conventional and molecular epidemiological tools.During the study period, 1152 infants were enrolled in the study. Prevalences of colonization by MDR GNB, ESBL-producing GNB and multiple species/genera averaged, respectively, 28.8%, 11.7%, and 3.7%. Prevalence and incidence density of colonization by MDR GNB and ESBL-producing GNB showed an upward trend through the surveillance period. Rates of ESBL-producing E coli and K pneumoniae colonization showed wide fluctuations peaking over the last 2 years. The only independent variables associated with colonization by MDR GNB and ESBL-producing organisms and multiple colonization were, respectively, the days of NICU stay (odds ratio [OR] 1.041), the days of exposure to ampicillin-sulbactam (OR 1.040), and the days of formula feeding (OR 1.031). Most clusters of E coli and K pneumoniae colonization were associated with different lineages. Ten out of 12 clusters had an outborn infant as their index case.Our study confirms that MDR GNB are an increasing challenge to NICUs. The universal once-a-week approach allowed us to understand the epidemiology of MDR GNB, to timely detect new clones and institute contact precautions, and to assess risk factors. Collection of these data can be an important tool to optimize antimicrobials use and control the emergence and dissemination of resistances in NICU

The burden of Candida species colonization in NICU patients: a colonization surveillance study

Fungal infections are an important cause of morbidity and mortality in neonatal intensive care units (NICUs). The identification of specific risk factors supports prevention of candidemia in neonates. Effective prophylactic strategies have recently become available, but the identification and adequate management of high-risk infants is still a priority. Prior colonization is a key risk factor for candidemia. For this reason, surveillance studies to monitor incidence, species distribution, and antifungal susceptibility profiles, are mandatory. Among 520 infants admitted to our NICU between January 2013 and December 2014, 472 (90.77%) were included in the study. Forty-eight out of 472 (10.17%) patients tested positive for Candida spp. (C.), at least on one occasion. All the colonized patients tested positive for the rectal swab, whereas 7 patients also tested positive for the nasal swab. Fifteen out of 472 patients (3.18%) had more than one positive rectal or nasal swab during their NICU stay. Moreover, 9 out of 15 patients tested negative at the first sampling, suggesting they acquired Candida spp. during their stay. Twenty-five of forty-eight (52.1%) colonized patients carried C.albicans and 15/48 (31.25%) C.parapsilosis. We identified as risk factors for Candida spp. colonization: antibiotic therapy, parenteral nutrition, the use of a central venous catheter, and nasogastric tube. Our experience suggests that effective microbiological surveillance can allow for implementing proper, effective and timely control measures in a highrisk setting

Rare chondrosarcoma of the breast treated with quadrantectomy instead of mastectomy. A case report

Breast chondrosarcoma is a rare sarcoma that mainly occurs in females >50 years old. To the best of our knowledge, only 16 cases were reported in the literature prior to 2013 and all patients were surgically treated by mastectomy, with or without lymphadenectomy, which was occasionally preceded by neoadjuvant chemotherapy. However, the literature does not report the benefit of mastectomy compared with a more conservative surgery. The present study reports a novel case of extraskeletal chondrosarcoma of the breast. A 63‑year‑old female patient presented with a neoplasm localized in the upper‑outer quadrant of the right breast. The palpable lesion with sharp margins was a firm parenchymatous mass, which was confirmed by ultrasonography and mammography. The patient underwent conservative quadrantectomy instead of mastectomy, followed by post‑surgical chemotherapy. A positron emission tomography scan performed five months subsequent to the surgery revealed no remnants of the disease. The patient underwent a strict clinical and instrumental follow‑up, and two and half years after surgery, there are no signs of recurrent disease. In conclusion, the present case is currently one of the two cases in which a more conservative quadrantectomy was performed, instead of mastectomy. This surgical approach did not lead to metastasis and resulted in a good follow‑up for the patient

Candida SPP. Colonization in NICU: A 2-Year Surveillance Study

Introduction: Fungal infections are an important cause of increased morbidity and mortality in infants admitted to neonatal intensive care units (NICUs). In VLBW infants, Candida (C.) albicans is the third most common cause of neonatal late onset sepsis (LOS). The overall incidence of candidemia in NICU is increasing because of the longer survival and the invasive procedures related with the intensive care of extremely preterm infants. Prevention of candidemia in neonates is supported by the identification and adequate management of specific risk factors, including low birth weight, use of invasive devices, prolonged hospitalization and use of broad-spectrum antimicrobial agents. Effective prophylactic strategies have recently become available, but the identification of the best possible strategies to manage high-risk infants is still a priority. Prior colonization is a key risk factor for candidemia. For this reason, surveillance studies to monitor incidence, species distribution, and antifungal susceptibility profiles are mandatory. Materials and Methods: In 2013 and 2014, we performed a cohort, prospective surveillance study in our NICU, collecting weekly nasal and rectal swabs. For each patient, clinical and demographic data expected to affect Candida colonization were recorded. We evaluated Candida spp. colonization rate and assessed the related risk factors. Swabs were placed on Sabouraud agar and incubated at 30°C for 4 days. Candida growth on agar was confirmed by microscopic observation. Moreover, Candida spp. were identified through Candida chromogenic agar (ChromAgar Candida, Laboratorios Conda) and API® 20C AUX (Biomérieux). Statistical analysis was performed by EpiInfo (CDC software) using the chi square or the Fisher’s exact method, when indicated. We assumed as statistically significant a p-value < 0.05. Results: In this 2-year study, we enrolled 520 patients and we analyzed 1,259 nasal and 1,255 rectal swabs. From 472 out of 520 patients we collected complete microbiological, clinical and demographic data. 48 out of 472 (10.17%) patients tested positive for Candida spp. at least once. In particular, 26 patients tested positive for C. albicans, 16 for C. parapsilosis, 6 for C. glabrata and 1 each for C. guilliermondii and an environmental mold. All the colonized patients had their rectal samples positive, and 7 their nasal samples as well. 15 patients out of 472 (3.18%) had more than one rectal or nasal swab positive during their NICU stay. Importantly, 9 patients out of 15 tested negative at the first sampling, suggesting that they have acquired Candida spp. colonization during their stay. Table 1 summarizes data about risk factors for Candida colonization in the patients under study. No systemic infection by Candida spp. was reported during the study. Conclusion: Our experience suggest that an effective microbiological surveillance can allow for implementing proper, effective and timely control measures in a high-risk setting

Retinoic Acid Specifically Enhances Embryonic Stem Cell Metastate Marked by Zscan4

Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation