Expression of Placental Neurotrophin-3 (NT-3) in Physiological Pregnancy, Preeclampsia and Chorioamnionitis

Neurotrophic factors are a group of proteins that act as paracrine and autocrine growth factors. They are involved in the regulation of morphogenesis and development of several tissues. The present study aims to evaluate, for the first time, the expression of Neurotrophin-3 in the human placenta during normal pregnancy and in preeclampsia and chorioamnionitis. Neurotrophin-3 mRNA, assessed by RT-PCR analysis in six term placentas, were observed in all the specimens examined. Neurotrophin-3 protein expression and tissue distribution was evaluated by immunohistochemistry in placenta samples from uncomplicated first trimester (n = 5) and term (n = 5) pregnancies as well as in specimens from preeclampsia (n = 5) and chorioamnionitis (n = 5). In first trimester specimens, strong immunoreactivity was present in villous stromal cells, in the cyto- and syncytiotrophoblast, in decidua cells and in endometrial glands. Third trimester specimens showed prominent immunostaining in cyto- and syncytiotrophoblast cells, in decidua cells and in the amniotic membranes. Villous stromal cells were weakly stained. Similar protein localization was observed in placentas with preeclampsia and chorioamnionitis. In the latter, however, positive villous stromal cells increased in number and in staining intensity when compared with controls and preeclampsia (p < 0.001). The roles of Neurotrophin-3 in pregnancy are presently unknown. A regulatory function on placenta and foetal brain development and maternal inflammatory response may be hypothesized

Extension implants in the atrophic posterior maxilla: 1-year results of a retrospective case-series

Background/purpose: Blade implants account for one of the most debated dental implants design in scientific literature. They have been reconsidered by clinicians since their re-classification by Food and Drug Administration in 2014. Materials and methods: The present study aimed to evaluate the outcome of newly manufactured extension implants in the treatment of moderate atrophic posterior maxillae. All the patients enrolled in the present retrospective case series study showed a moderate bone atrophy in the posterior maxilla with a maximum residual height ranging between 4 mm and 8 mm. Implants were inserted with the aid of an electro-magnetic device, and then they covered with screws and left healing. Three months after, implants were exposed and loaded. Results: Difference between the marginal bone level at the 3-month evaluation (5.57 ± 0.67 mm) and that at baseline (5.67 ± 0.55 mm) appeared to be not significant (p-value = 0.63). At the 12-month evaluation, the marginal bone level (4.95 ± 0.45 mm) underwent significant decrease respect to baseline value as proven by significant change at marginal bone level (−0.62 ± 0.51 mm with a p-value = 0.01). Conclusion: The results of the present study suggested a positive 12-month outcome for extension implants in the rehabilitation of the moderate atrophic maxilla, without the need of extensive reconstructive surgeries and grafting procedures

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C - both symptomatic and asymptomatic - have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment

Analysis of tight junctions in placentas affected by chorioamnionitis: in vivo and in vitro analysis

The human placenta and fetal membranes provide a barrier regulating the transfer of materials between the mother and the developing fetus throughout gestation. Chorioamnionitis is an important risk factor for preterm delivery that is associated with high perinatal morbidity and mortality. Chorioamnionitis is the term applied to infections of the placenta and membranes resulting in high concentrations of IL- 1beta, IL-6, IL-8 and TGF-beta in the amniotic fluid (D’Alquen et al., 2005). With progression of inflammation, immune cells penetrate blood vessels and infiltrate the umbilical cord, resulting in funisitis (Romero and Mazor, 1988). In normal conditions the two important physical entities in endothelial/epithelial paracellular clefts are adherens junctions and tight junctions. Tight junction governs the paracellular movement of water, solutes and immune cells, through the intercellular space creating a boundary between the apical and basolateral sides of cellular barriers (Gruenheid and Finlay, 2003). We have evaluated the localization of tight junctions studying the Zonula Occludens-1 (ZO-1) and Occludin expressions as well as the localization of adherent junctions, testing the expression of VE-cadherin and beta-catenin in placentas from normal gestations, from preterm idiopathic deliveries and from chorioamnionitis by immunohistochemistry. In addition, we have evaluated the mRNAs by real time PCR, the protein levels of these molecules by Western blot analysis in placental tissues, and to better clarify the action of some cytokines on occludin we performed in vitro analysis of HUVEC cultures. Our more striking result is the decrease of occludin expression in placentas from chorioamnionitis and an evident action of the cytokines on this molecule

Raf Kinase Inhibitor Protein (RKIP) expression and function in human myometrium and leiomyoma

Many growth factors been identified in human myometrium and leiomyoma and activate multiple signaling pathways in order to regulate major cellular processes, including proliferation and fibrosis which are linked to uterine leiomyoma development and growth. The Raf kinase inhibitor protein (RKIP) has emerging roles as regulator of multiple signaling networks including mitogen activated protein (MAP) kinase cascade, as well as interaction with glycogen synthase kinase 3 (GSK3). In our study, we aimed to investigate the presence of RKIP in human myometrium and leiomyoma as well as to determine the effect of locostatin (RKIP inhibitor) on extracellular matrix (ECM) production, proliferation and migration in human myometrial and leiomyoma cells. Myometrial and leiomyoma tissues were used to investigate the localization and the expression level of RKIP through immunohistochemistry and western blotting. Myometrial and leiomyoma cells were treated with locostatin to measure ECM expression by real time PCR, GSK3b expression by western blotting, cell migration by wound-healing assay and cell proliferation by MTT assay. We found that RKIP is expressed in human myometrial and leiomyoma tissue. Locostatin treatment resulted in the activation of the MAPK signal pathway (ERK phosphorylation), providing a powerful validation of our targeting protocol. Further, RKIP inhibition by locostatin reduces ECM components. Moreover, the inhibition of RKIP by locostatin impaired cell proliferation and migration in both leiomyoma and myometrial cells. Finally, locostatin treatment reduced GSK3β expression. Therefore, even if the activation of MAPK pathway should increase proliferation and migration, the destabilization of GSK3β leads to the reduction of proliferation and migration of myometrial and leiomyoma cells

Array comparative genomic hybridization in retinoma and retinoblastoma tissues

In retinoblastoma, two RB1 mutations are necessary for tumor development. Recurrent genomic rearrangements may represent subsequent events required for retinoblastoma progression. Array-comparative genomic hybridization was carried out in 18 eye samples, 10 from bilateral and eight from unilateral retinoblastoma patients. Two unilateral cases also showed areas of retinoma. The most frequent imbalance in retinoblastomas was 6p gain (40%), followed by gains at 1q12-q25.3, 2p24.3-p24.2, 9q22.2, and 9q33.1 and losses at 11q24.3, 13q13.2-q22.3, and 16q12.1-q21. Bilateral cases showed a lower number of imbalances than unilateral cases (P = 0.002). Unilateral cases were divided into low-level (≤4) and high-level (÷7) chromosomal instability groups. The first group presented with younger age at diagnosis (mean 511 days) compared with the second group (mean 1606 days). In one retinoma case ophthalmoscopically diagnosed as a benign lesion no rearrangements were detected, whereas the adjacent retinoblastoma displayed seven aberrations. The other retinoma case identified by retrospective histopathological examination shared three rearrangements with the adjacent retinoblastoma. Two other gene-free rearrangements were retinoma specific. One rearrangement, dup5p, was retinoblastoma specific and included the SKP2 gene. Genomic profiling indicated that the first retinoma was a pretumoral lesion, whereas the other represents a subclone of cells bearing 'benign' rearrangements overwhelmed by another subclone presenting aberrations with higher 'oncogenic' potential. In summary, the present study shows that bilateral and unilateral retinoblastoma have different chromosomal instability that correlates with the age of tumor onset in unilateral cases. This is the first report of genomic profiling in retinoma tissue, shedding light on the different nature of lesions named 'retinoma'. (Cancer Sci 2009; 100: 465–471

The Relationship Between Infertility, Infertility Treatment, Psychological Interventions, and Posttraumatic Stress Disorder

The number of women diagnosed as infertile continues to grow every year. The psychological impact of the infertility experience has been said to create distress equivalent to that associated with life-threatening illnesses and has been linked with posttraumatic stress disorder (PTSD). Using shattered assumption and stress-buffering theory, this quantitative causal comparative study explored the potential functional relationship between infertility and PTSD. The majority of the (all-female) participants were 24- to 34-year-old college graduates. A 2 X 3 factorial between-subjects ANOVA examined and compared the cause and effect of the independent variables, fertility treatment and psychological intervention, on the dependent variable, PTSD. A multiple linear regression was conducted to understand PTSD symptomology scores. The results revealed that the type of infertility treatment does not impact PTSD symptomatology in medically diagnosed women. However, the main effect of psychological treatment was significant, as was infertility treatment by psychological treatment interaction. Additionally, the impact of fertility problems on the participant\u27s physical health was the highest ranking predictor, which suggests that stress levels in women receiving infertility treatment are equivalent to those in women with cancer, AIDS, and heart disease, as suggested by other researchers. This study has implications for positive social change, in that it may promote better understanding of the psychological impact of infertility and decreased PTSD symptomatology for medically diagnosed infertile women. It opens the door for future research about the effectiveness of psychological intervention, and provides awareness of possible PTSD susceptibility

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Cowboy innamorati e ladri ammogliati. Semiotica del fumetto caricaturale francese

Tra tutte le discipline che si sono interessate al mondo del fumetto, la semiotica ha il merito di aver offerto gli strumenti più elaborati per indagare il senso ultimo del testo su diversi piani, dall’elemento grafico a quello più strettamente narrativo. Nell’ambito di questo percorso di ricerca, tali principi hanno rappresentato gli strumenti principali per indagare più nel dettaglio la dimensione del fumetto parodico-caricaturale, con particolare riguardo per l’approccio della semiotica passionale. Concentrandosi in particolare sulla produzione fumettistica francese, la ricerca ha tratteggiato i contorni della storia della caricatura, per poi addentrarsi nell’analisi semiotica di alcuni casi di studio particolarmente rilevanti. Tra questi, fondamentale è stato il riferimento all’atipico western di Christophe Blain, Gus: un’opera che gioca con la dimensione grafica per costruire molteplici livelli di senso, trascinando il lettore in una costruzione testuale elaborata, nascosta dietro l’apparente leggerezza delle vicende antieroiche di cowboy innamorati e ladri ammogliati