Adipocytes sustain pancreatic cancer progression through a non-canonical WNT paracrine network inducing ROR2 nuclear shuttling.

BACKGROUND: Solid epidemiological evidences connect obesity with incidence, stage and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions. METHODS: We studied the role of factors secreted by two adipogenic model systems from primary human bone marrow stromal cells (hBMSCs) in an in vitro experimental cell transformation model system of human pancreatic ductal epithelial (HPDE) cell stably expressing activated KRAS (HPDE/KRAS),Results:We measured a significant induction of EMT and aggressiveness in HPDE and HPDE/KRAS cell lines when cultured with medium conditioned by fully differentiated adipocytes (ADIPOCM) if compared with the same cells cultured with medium conditioned by hBMSC (hBMSCCM) from two different healthy donors. Several genes coding for soluble modulators of the non-canonical WNT signaling pathway, including FRZB, SFRP2, RSPO1, WNT5A and 5B were significantly overexpressed in fully differentiated adipocytes than in their respective in hBMSC. ADIPOCM induced the overexpression and the nuclear translocation of the Frizzled family member receptor tyrosine kinase-like orphan receptor (Ror) 2 in HPDE and HPDE/KRAS cells. Vantictumab, an anti-Frizzled monoclonal antibody, reduced ROR2 nuclear translocation and in turn the EMT and aggressiveness in HPDE and HPDE/KRAS cells. CONCLUSIONS: We demonstrated that adipocytes could induce EMT and aggressiveness in models of pancreatic preneoplastic lesions by orchestrating a complex paracrine signaling of soluble modulators of the non-canonical WNT signaling pathway that determine, in turn, the activation and nuclear translocation of ROR2. This signaling pathway could represent a novel target for pancreatic cancer chemoprevention. Most importantly, these factors could serve as novel biomarkers to select a risk population among obese subjects for screening and, thus, early diagnosis of pancreatic cancer.

Abdominal Hernias, Giant Colon Diverticulum, GIST, Intestinal Pneumatosis, Colon Ischemia, Cold Intussusception, Gallstone Ileus, and Foreign Bodies: Our Experience and Literature Review of Incidental Gastrointestinal MDCT Findings.

Incidental gastrointestinal findings are commonly detected on MDCT exams performed for various medical indications. This review describes the radiological MDCT spectrum of appearances already present in the past literature and in today's experience of several gastrointestinal acute conditions such as abdominal hernia, giant colon diverticulum, GIST, intestinal pneumatosis, colon ischemia, cold intussusception, gallstone ileus, and foreign bodies which can require medical and surgical intervention or clinical follow-up. The clinical presentation of this illness is frequently nonspecific: abdominal pain, distension, nausea, fever, rectal bleeding, vomiting, constipation, or a palpable mass, depending on the disease. A proper differential diagnosis is essential in the assessment of treatment and in this case MDCT exam plays a central rule. We wish that this article will familiarize the radiologist in the diagnosis of this kind of incidental MDCT findings for better orientation of the therapy.

Impact of 2013 ASCO/CAP guidelines on HER2 determination of invasive breast cancer: A single institution experience using frontline dual-color FISH.

PURPOSE: The new ASCO/CAP guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2-FISH, introducing the most controversial change to the HER2-equivocal category. We retrospectively evaluated the impact of AC2013 in a cohort of consecutive invasive breast cancers (IBCs) analyzed with frontline dual-color FISH. METHODS: 2788 consecutive IBCs were reclassified based on the AC2013 guidelines. Clinico-pathological features of equivocal IBCs were compared with HER2-negative and HER2-positive IBCs. FISH HER2-equivocal cases underwent reflex tests: HER2-IHC, RARA-FISH, and SMS-FISH. Overall and disease-free survivals were evaluated in AC2007 HER2-positive patients treated with trastuzumab and in patients that became eligible for target-therapy according to AC2013. RESULTS: Two-hundred HER2-negative cases (7.2%) were classified differently, following AC2013: 0.3% (8/2788) became HER2-positive and 6.9% (192/2788) HER2-equivocal. AC2013, compared with AC2007, significantly increased initial HER2-equivocal cases (6.9%vs1.6%, p < 0.001). AC2013 equivocal-IBCs affected older patients and showed pathological features between HER2-negative and HER2-positive IBCs. After reflex tests, 102 of the 190 equivocal cases (53.7%) were reclassified as HER2-positive, 51 (26.8%) as negative and 37 (19.5%) as equivocal. IHC tested negative in 44.7% of cases, whereas SMS-FISH showed the highest percentage of positive results (45.8%). Clinical outcomes showed no statistically significant differences. CONCLUSION: Overall, 80.5% of FISH-equivocal cases were solved with at least one reflex test and 3.6% of patients became AC2013 HER2-positive, therefore eligible for target-therapy, but showed clinical outcomes similar to HER2-positive patients treated with trastuzumab. Our data belittle the clinical impact of AC2013 HER2-equivocal reclassification; further prospective randomized clinical studies are necessary to support these findings.

Molecular targets of developmental exposure to bisphenol A in diabesity: a focus on endoderm-derived organs.

Several studies associate foetal human exposure to bisphenol A (BPA) to metabolic/endocrine diseases, mainly diabesity. They describe the role of BPA in the disruption of pancreatic beta cell, adipocyte and hepatocyte functions. Indeed, the complexity of the diabesity phenotype is due to the involvement of different endoderm-derived organs, all targets of BPA. Here, we analyse this point delineating a picture of different mechanisms of BPA toxicity in endoderm-derived organs leading to diabesity. Moving from epidemiological data, we summarize the in vivo experimental data of the BPA effects on endoderm-derived organs (thyroid, pancreas, liver, gut, prostate and lung) after prenatal exposure. Mainly, we gather molecular data evidencing harmful effects at low-dose exposure, pointing to the risk to human health. Although the fragmentation of molecular data does not allow a clear conclusion to be drawn, the present work indicates that the developmental exposure to BPA represents a risk for endoderm-derived organs development as it deregulates the gene expression from the earliest developmental stages. A more systematic analysis of BPA impact on the transcriptomes of endoderm-derived organs is still missing. Here, we suggest in vitro toxicogenomics approaches as a tool for the identification of common mechanisms of BPA toxicity leading to the diabesity in organs having the same developmental origin.

Surgical management of advanced gastric cancer: An evolving issue.

Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer.

A review of the pattern of AIDS defining, HIV associated neoplasms and premalignant lesions diagnosed from 2000-2011 at Kenyatta National Hospital, Kenya.

BACKGROUND: Sub-Sahara Africa hosts up to 71 % of all HIV infected people in the world. With this high incidence of Human immunodeficiency virus ( HIV) comes the burden of co-morbidities such as malignant and premalignant lesions. Aids defining malignancies have been listed as Kaposi's sarcoma, Non-Hodgkin's lymphoma and invasive squamous cell carcinoma of the cervix. People with HIV/AIDS(PLWAS) have a higher risk of developing these neoplasms than the rest of the population. The pathogenesis of these neoplasms in people with HIV has been linked to immune suppression, persistent antigenic stimulation and cytokine dysregulation. Current study analyzes and presents the patterns and trends in the presentation of HIV related malignancies in patients diagnosed through histopathology at Kenyatta National Hospital. AIM: To describe the patterns of AIDS- defining and non-AIDS- defining malignancies and premalignant lesions 10 years pre- and post HAART period at Kenyatta National hospital, Kenya. METHODS AND TECHNIQUES: This was a hospital based descriptive cross sectional study. The Formalin fixed paraffin embedded (FFPE) blocks and histological reports of patients diagnosed between 2000 and 2011 were traced from archives. The patients' demographic data and clinical presentation was entered in an excel spreadsheet and the diagnosis and coding confirmed by a histopathologist. The data was then cleaned and analyzed using SSPS version 17.0 Ink. RESULTS: A total of 173 lesions were reviewed and analyzed. Of these 118 (68 %) were from females and 55 from males (32 %). The male to female ratio was 1:2. The age range was from two to 56 years with a median of 36 years. Kaposi sarcoma is the leading AIDS defining malignancy in Kenya while invasive squamous cell carcinoma of the conjunctiva is the leading non-AIDS defining malignancy. This is closely followed by invasive squamous cell carcinoma of the cervix and NHL. CONCLUSION: Kaposi sarcoma is the leading AIDS associated neoplasm in Kenya. Physicians and caretakers managing and following up on HIV/AIDS patients should look out for Kaposi sarcoma as a form of IRIS following the institution of HAART in all HIV/AIDS patients. The incidence of invasive squamous cell carcinoma of the conjunctiva is increasing in PLWAS in Kenya. There is therefore a need to introduce early screening programs for squamous intraepithelial neoplasm of the conjunctiva in HIV/AIDS patients.

Oncological safety of breast cancer patients undergoing free-flap reconstruction and lipofilling.

BACKGROUND: Autologous fat grafting is a widely accepted approach for breast reconstruction after mastectomy but its oncological safety has not been established. This study aimed to compare recurrence in patients who underwent fat-grafting procedures after autologous breast reconstruction and those who did not. PATIENTS AND METHODS: We retrospectively reviewed 207 consecutive patients, who underwent mastectomy and reconstruction using free flap surgery. We divide them in two groups: a study group of patients who underwent fat grafting procedure and a control group of patients who did not. Outcome regarding local and regional recurrence was compared between the two groups. Particularly, we studied recurrences from primary surgery to baseline (first lipofilling) and from baseline to most recent follow-up. RESULTS: Median follow-up was 60 months from surgery to baseline and 29 months from baseline to most recent follow-up. The overall observational period after mastectomy in the control group was 120 months. Local recurrence was observed in 6 patients from the study group, respectively 3 in the first observational period and 3 after the fat grafting procedure. The control group, as the study one, presented a total of 6 recurrences (p = 0.555; Hazard Ratio free flap and lipo vs only free flap: = 0.66; 95% CI 0.16-2.66). CONCLUSIONS: We found no significant differences in recurrence between patients who underwent fat grafting and those who did not. These encouraging findings support previous results but larger series of patients are required to confirm long-term oncological safety in these procedures.

Breast metastases from a Renal Cell Carcinoma. A case report and review of the literature.

INTRODUCTION: Metastases to the breast from extra-mammary tumors are uncommon and few sporadic cases are reported in the international literature. An accurate differential diagnosis of secondary cancer is mandatory because both prognosis and treatment differ with respect to primary breast tumors. PRESENTATION OF CASE: We present the case of a 70-year-old woman with an isolated metastasis to the breast occuring 9 years after undergoing a nephrectomy for Renal Cell Carcinoma (RCC). Clinical examination revealed a palpable and mobile mass in the right breast with an enlarged ipsilateral axillary lymph node. Mammographic findings showed a dense, well circumscribed solid mass and the breast ultrasonography findings were those of a hypoechoic homogeneous solid nodule with no posterior attenuation but with prominent peripheral vascularity. A tru-cut biopsy was conclusive for a metastatic deposit by RCC. A whole-body CT scan showed no evidence of further recurrences. The patient underwent metastasectomy and exeresis of the papable lymphnode. DISCUSSION: In patients with former surgery for RCC, a diagnosis based on a preoperative biopsy allows to indicate the proper surgical treatment: in facts, as compared to primary breast tumors treatment, the rationale to pursue wide surgical margins is pointless in cases of metastases and, similarly, the biopsy of the sentinel lymphnode is void of sense due to the lack of its physiopathological prerequisite. CONCLUSION: We suggest to consider a micro-histological biopsy of any new breast lesion appearing in a patient with a history of treatment for RCC. Prompt diagnosis is necessary to choose the right treatment.

Nitric oxide synthase evaluation in oral precancerous and cancerous lesions.

Nitric Oxide (NO) has been linked to several cardiovascular, neurological and immunological physiological and pathological functions. Several studies have shown that the eNOS, nNOS and iNOS effects on cancer cell growth and proliferation are related to the upregulation of the Wnt pathway and have a central role during metastasis development. Recent studies suggest that cancer cells undergo metabolic reprogramming, which drives cancer cell growth and progression. The aim of this study was to observe the NOS activity in the pathogenesis of oral precancerous and cancerous lesions. The results showed changes in eNOS activity levels, which increased from healthy oral mucosa to oral squamous cell carcinoma SCC, through different dysplasia levels. The iNOS activity levels increased in precancerous lesions compared to healthy mucosa, where iNOS was absent, while it decreased in SCC lesions. Moreover, a gradual increase of nNOS activity together with the progression of the lesions was also found. These results may suggest how NO could play a critical role during pathogenesis, growth and development of precancerous lesions to cancer degeneration.

Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. New insights into the pathogenesis of Burkitt lymphoma.

Epstein-Barr Virus (EBV) is a γ-herpesvirus that infects >90% of the human population. Although EBV persists in its latent form in healthy carriers, the virus is also associated with several human cancers. EBV is strongly associated with Burkitt lymphoma (BL), even though there is still no satisfactory explanation of how EBV participates in BL pathogenesis. However, new insights into the interplay between viruses and microRNAs (miRNAs) have recently been proposed. In particular, it has been shown that B-cell differentiation in EBV-positive BL is impaired at the post-transcriptional level by altered expression of hsa-miR-127. Here, we show that the overexpression of hsa-miR-127 is due to the presence of the EBV-encoded nuclear antigen 1 (EBNA1) and give evidence of a novel mechanism of direct regulation of the human miRNA by this viral product. Finally, we show that the combinatorial expression of EBNA1 and hsa-miR-127 affects the expression of master B-cell regulators in human memory B cells, confirming the scenario previously observed in EBV-positive BL primary tumors and cell lines. A good understanding of these mechanisms will help to clarify the complex regulatory networks between host and pathogen, and favor the design of more specific treatments for EBV-associated malignancies.

The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma.

Sporadic Burkitt lymphoma (sBL) can be delineated from diffuse large B-cell lymphoma (DLBCL) by a very homogeneous mRNA expression signature. However, it remained unclear whether all three BL variants-sBL, endemic BL (eBL) and human immunodeficiency virus-associated BL (HIV-BL)-represent a uniform biological entity despite their differences in geographical occurrence, association with immunodeficiency and/or incidence of Epstein-Barr virus (EBV) infection. To address this issue, we generated micro RNA (miRNA) profiles from 18 eBL, 31 sBL and 15 HIV-BL cases. In addition, we analyzed the miRNA expression of 86 DLBCL to determine whether miRNA profiles recapitulate the molecular differences between BL and DLBCL evidenced by mRNA profiling. A signature of 38 miRNAs containing MYC regulated and nuclear factor-kB pathway-associated miRNAs was obtained that differentiated BL from DLBCL. The miRNA profiles of sBL and eBL displayed only six differentially expressed miRNAs, whereas HIV and EBV infection had no impact on the miRNA profile of BL. In conclusion, miRNA profiling confirms that BL and DLBCL represent distinct lymphoma categories and demonstrates that the three BL variants are representatives of the same biological entity with only marginal miRNA expression differences between eBL and sBL.

Vascular endothelial growth factor enhances in vitro proliferation and osteogenic differentiation of human dental pulp stem cells.

Mesenchymal stem cells (MSC), isolated from dental tissues, are largely studied for future application in regenerative dentistry. In this study, we used MSC obtained from human dental pulp (DPSC) of normal impacted third molars that, when cultured in lineage-specific inducing media, differentiate into osteoblasts and adipocytes (evaluated by Alizarin Red S and Red Oil O stainings, respectively), thus showing a multipotency. We confirmed that DPSC, grown under undifferentiating conditions, are negative for hematopoietic (CD45, CD31, CD34, CD144) and positive for mesenchymal (CD29, CD90, CD105, CD166, CD146, STRO-1) markers, that underwent down-regulation when cells were grown in osteogenic medium for 3 weeks. In this condition, they also exhibit an increase in the expression of osteogenic markers (RUNX-2, alkaline phosphatase) and extracellular calcium deposition, whereas the expression of receptors (VEGFR-1 and -2) for vascular endothelial growth factors (VEGF) and related VEGF binding proteins was similar to that found in undifferentiated DPSC. Exposure of DPSC growing under undifferentiating or osteogenic conditions to VEGF-A165 peptide (10-40 ng/ml) for 8 days dose- and time-dependently increased the number of proliferating cells without inducing differentiation towards endothelial lineage, as evaluated by the lack of expression of specific markers (CD31, CD34, CD144). Additionally, exposure of DPSC cultured in osteogenic medium to VEGF-A165 for a similar period enhanced cell differentiation towards osteoblasts as evaluated after 14 and 21 days by Alizarin Red S staining and alkaline phosphatase activity quantification. These findings may have clinical implications possibly facilitating tissue repair and remodeling.

Phase diagram of electron systems near the superconductor-insulator transition.

The zero temperature phase diagram of Cooper pairs exposed to disorder and a magnetic field is determined theoretically from a variational approach. Four distinct phases are found: a Bose and a Fermi insulating, a metallic, and a superconducting phase, respectively. The results explain the giant negative magnetoresistance found experimentally in In-O, TiN, Be and high-T(c) materials.

MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation.

The molecular feature of Burkitt lymphoma (BL) is the translocation that places c-Myc under the control of immunoglobulin gene regulatory elements. However, there is accumulating evidence that some cases may lack an identifiable MYC translocation. In addition, during the EUROFISH project, aiming at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer and their association with fragile sites in the genome. They have also been shown to control cell growth, differentiation, and apoptosis, suggesting that these molecules could act as tumour suppressors or oncogenes. Our results demonstrated a modulation of specific miRNAs. In particular, down-regulation of hsa-let-7c was observed in BL cases, compared to normal controls. More interestingly, hsa-mir-34b was found to be down-regulated only in BL cases that were negative for MYC translocation, suggesting that this event might be responsible for c-Myc deregulation in such cases. This hypothesis was further confirmed by our in vitro experiments, which demonstrated that increasing doses of synthetic hsa-mir-34b were able to modulate c-Myc expression. These results indicate for the first time that hsa-mir-34b may influence c-Myc expression in Burkitt lymphoma as the more common aberrant control exercised by the immunoglobulin enhancer locus.

Distribution and ecological relevance of fine sediments in organic-enriched lagoons: the case study of the Cabras lagoon (Sardinia, Italy).

In organic-enriched sedimentary systems, like many Mediterranean coastal lagoons, a detailed analysis of sediment grain size composition and partitioning within the muds is crucial to investigate sedimentological trends related to both hydrodynamic energy and basin morphology. In these systems, sediment dynamics are particularly important because the partitioning and transport of fine sediments can strongly influence the redistribution and accumulation of large amounts of organic matter, and consequently the distribution of benthic assemblages and the trophic status and functioning of a lagoon. Nevertheless, studies on benthic-sediment relationships have been based mainly on a rather coarse analysis of sediment grain size features. In muddy systems, however, this approach may impede a proper evaluation of the relationships and effects of the distribution of fine sediment and organic matter on the biotic benthic components. Here we show that the distribution of sedimentary organic matter (OM) and total organic carbon (TOC) in the Cabras lagoon (Sardinia, Italy) can be explained (i.e., predicted) as a function of a nonlinear increase in the amount of the cohesive fraction of sediments (< or = 8 microm grain size particles) and that this fraction strongly influences the structure, composition and distribution of macrobenthic assemblages. Even in such a homogeneously muddy system, characterized by "naturally" occurring impoverished communities, impaired benthic assemblages were found at < or = 8 microm, OM, TOC contents of about 77%, 11% and 3.5%, respectively. A review of studies conducted in Mediterranean coastal lagoons highlighted a lack of direct integrated analysis of sediment features and the biotic components. We suggest that, especially in organic-enriched coastal lagoons, monitoring programs should primarily investigate and consider the cohesive fraction of sediments in order to allow a better assessment of benthic-sediment relationships and ecological quality of the system.

HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas.

Angiogenic switch marks the beginning of tumor's strategy to acquire independent blood supply. In some subtypes of non-Hodgkin's lymphomas, higher local vascular endothelial growth factor (VEGF) expression correlates with increased microvessel density. However, this local VEGF expression is higher only in tumors with elevated expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. Several studies have indicated that VEGF receptors are also targeted by Tat protein from the HIV-1-infected cells. Given the similarity of the basic region of Tat to the angiogenic factors (basic fibroblast growth factor, VEGF), Tat mimics these proteins and binds to their receptors. We evaluated the role of HIV-1 Tat in regulating the level of VEGF expression and microvessel density in the AIDS-related diffuse large B-cell (DLBCL) and Burkitt lymphomas (BL). By luciferase assay, we showed that VEGF promoter activity was downregulated in vitro in cells transfected with Tat. Reduced VEGF protein expression in primary HIV-1 positive BL and DLBCL, compared to the negative cases, supported the findings of promoter downregulation from the cell lines. Microvascular density assessed by CD34 expression was, however, higher in HIV-1 positive than in HIV-1 negative tumors. These results suggest that Tat has a wider angiogenic role, besides the regulation of VEGF expression. Thus, targeting Tat protein itself and stabilizing transient silencing of VEGF expression or use of monoclonal antibodies against their receptors in the AIDS-associated tumors will open a window for future explorable pathways in the management of angiogenic phenotypes in the AIDS-associated non-Hodgkin's lymphomas.

Hepatic artery aneurysm rupture in a woman with primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis. However, a small number of patients present with visceral aneurysms. Although such aneurysms are rare, their presence in patients who are usually treated with lifelong anticoagulation raises important therapeutic problems, in view of the risk of aneurysm rupture and acute abdominal hemorrhage. We report the case of a young woman with APS who presented with abdominal bleeding due to ruptured common hepatic artery aneurysm. She was successfully treated by proximal ligation. The features of such aneurysms are discussed.

Placental neurokinin B mRNA expression increases at preterm labor.

INTRODUCTION: Neurokinin B (NKB) is a neuropeptide belonging to the family of tachykinins-related peptides that elicits contractility of human myometrial strips in vitro. The present study evaluates whether placental mRNA and peptide expression of NKB change in women at preterm labor. METHODS: A group of 26 women with singleton pregnancies were enrolled in the study. Placental tissue specimens were collected from pregnant women delivering after elective cesarean section, after labor at term, or after preterm labor. Changes in placental NKB mRNA and protein expression were evaluated by real-time quantitative RT-PCR analysis and by immunofluorescence respectively. RESULTS: Placental mRNA expression of NKB was significantly higher after term and preterm labor (P<0.001) than cesarean section, and highest after preterm labor. Immunofluorescent staining in placentas from preterm or term labor was more intense than after cesarean section (P<0.001). In particular, NKB protein expression was higher in placentas collected after preterm labor than those collected after term labor. DISCUSSION: Neurokinin B mRNA and protein are highly expressed in placenta at term and preterm labor; thus, the involvement of this neuropeptide in the events cascade leading to parturition may be suggested.

Sediment characteristics and macrofauna distribution along a human-modified inlet in the Gulf of Oristano (Sardinia, Italy).

We studied the spatial variability and within-year temporal changes in hydrological features, grain size composition and chemical characteristics of sediments, as well as macrofaunal assemblages, along a heavily modified inlet in the Gulf of Oristano (western Sardinia, Italy). The inlet connects the Cabras lagoon to the gulf through a series of convoluted creeks and man-made structures, including a dam and fish barriers built in the last three decades. Sediments were muddy and mainly composed of the "non-sortable" fraction (i.e., <8 microm particle size) in all four areas investigated: Lagoon, Creeks, Channel and Seaward. Along the inlet, however, the ratio between the <8 microm and the 8-64 microm fractions was highest in Creeks and Channel, between the fish barriers and the dam, suggesting impaired hydrodynamics. Consistently, steep gradients in water salinity, temperature and dissolved oxygen concentrations were found in proximity to the fish barriers. The whole inlet was characterized by a major organic enrichment of sediments, with up to an annual mean of 33.6% of organic matter and 11.7% of total organic carbon in Seaward due to the presence of seagrass leaf litter. Acid-volatile sulphide and chromium-reduced sulphur concentrations were highest throughout the year in Seaward and Lagoon, respectively, with a peak in summer. Consistently, the whole inlet supported low structured macrofaunal assemblages dominated by few opportunist species, with a relatively lower diversity in Lagoon throughout the year and the highest abundances in Seaward in summer. We infer that the presence of artificial structures along the inlet, such as fish barriers and the dam, impair the lagoon-gulf hydrodynamics, sediment exchange and animal recruitment and colonization. We suggest that the removal of these structures would favour water renewal in the Cabras lagoon, but would also increase the outflow of organic C-bonding fine particles into the gulf with serious consequences for Posidonia oceanica and Cymodocea nodosa seagrass meadows. We conclude that all possible consequences of such initiatives should be carefully considered before any action is taken.