Acute mesenteric ischemia in the emergency department: a retrospective analysis to develop a clinical diagnostic tool and a prospective validation study supported by duplex ultrasound

Acute mesenteric ischemia in the emergency department: a retrospective analysis to develop a clinical diagnostic tool and a prospective validation study supported by duplex ultrasoun

An alarming deterioration of neurological status

This clinical case should make us reflect on the potential dangers of lithium, often too readily prescribed by non expert physicians to elderly, and often poorly compliant, patients. There also needs to be very close monitoring of plasma lithium levels, in addition to paying attention to clinical signs, such as a persistent polyuria or hyperosmolarity, because these could be important early warning signs. It is therefore useful to reiterate that, in case of lithium intoxication with altered neurological status despite improvement blood tests, it is necessary to consider pontine or extra-pontine myelinolysis as a rare but possible complicatio

Placental thrombomodulin expression in recurrent miscarriage

<p>Abstract</p> <p>Background</p> <p>Early pregnancy loss can be associated with trophoblast insufficiency and coagulation defects. Thrombomodulin is an endothelial-associated anticoagulant protein involved in the control of hemostasis and inflammation at the vascular beds and it's also a cofactor of the protein C anticoagulant pathway.</p> <p>Discussion</p> <p>We evaluate the Thrombomodulin expression in placental tissue from spontaneous recurrent miscarriage and voluntary abortion as controls. Thrombomodulin mRNA was determined using real-time quantitative polymerase chain reaction. Reduced expression levels of thrombomodulin were found in recurrent miscarriage group compared to controls (1.82-fold of reduction), that corresponds to a reduction of 45% (from control group Delta CT) of thrombomodulin expression in spontaneous miscarriage group respect the control groups.</p> <p>Summary</p> <p>We cannot state at present the exact meaning of a reduced expression of Thrombomodulin in placental tissue. Further studies are needed to elucidate the biological pathway of this important factor in the physiopathology of the trophoblast and in reproductive biology.</p

Identification and Characterization of Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma Cell Lines

Background/Aims: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. Methods: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. Results: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Conclusion: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy

The successful introduction of an adapted form of the mini extra corporeal circulation used for cardiac surgery in an obese patient

Obese patients undergoing cardiac surgery have been shown to have a high risk of developing postoperative complications, specifically: increased length of hospital stay, readmission to intensive care unit, acute renal failure, deep sternal wound infections and new onset of atrial fibrillation

Inhibition of ERK1/2 signaling prevents bone marrow fibrosis by reducing osteopontin plasma levels in a myelofibrosis mouse model

Clonal myeloproliferation and development of bone marrow (BM) fibrosis are the major pathogenetic events in myelofibrosis (MF). The identification of novel antifibrotic strategies is of utmost importance since the effectiveness of current therapies in reverting BM fibrosis is debated. We previously demonstrated that osteopontin (OPN) has a profibrotic role in MF by promoting mesenchymal stromal cells proliferation and collagen production. Moreover, increased plasma OPN correlated with higher BM fibrosis grade and inferior overall survival in MF patients. To understand whether OPN is a druggable target in MF, we assessed putative inhibitors of OPN expression in vitro and identified ERK1/2 as a major regulator of OPN production. Increased OPN plasma levels were associated with BM fibrosis development in the Romiplostim-induced MF mouse model. Moreover, ERK1/2 inhibition led to a remarkable reduction of OPN production and BM fibrosis in Romiplostim-treated mice. Strikingly, the antifibrotic effect of ERK1/2 inhibition can be mainly ascribed to the reduced OPN production since it could be recapitulated through the administration of anti-OPN neutralizing antibody. Our results demonstrate that OPN is a novel druggable target in MF and pave the way to antifibrotic therapies based on the inhibition of ERK1/2-driven OPN production or the neutralization of OPN activity

On the Role of the Balance of GPCR Homo/ Heteroreceptor Complexes in the Brain

The early work on neuropeptide-monoamine receptor-receptor interactions in the Central Nervous System gave the first indications of the existence of G protein-coupled receptors (GPCRs) heteroreceptor complexes and the GPCR field began to expand from monomers into heteromers and higher order heteromers, including also GPCR-ion channel, Receptor Tyrosine Kinases (RTK)-GPCR and Receptor activity-modifying proteins-GPCR heteroreceptor complexes. The existence of heteroreceptor complexes with allosteric receptor-receptor interactions increases the diversity of receptor function including recognition, trafficking and signalling. We have proposed the molecular phenomenon of receptor-receptor interactions as a good way to understand of how brain function can increase through molecular integration of signals. An alteration in specific receptor-receptor interactions or their balance/equilibrium (with the corresponding monomers-homomers) are indeed considered to have a role in the pathogenic mechanisms that lead to various diseases, including drug addiction, depression, Parkinson's disease and schizophrenia. Therefore, targeting protomer-protomer interactions in heteroreceptor complexes or the balance with their corresponding homoreceptor complexes in discrete brain regions may become an important field for developing novel drugs, including heterobivalent drugs and optimal types of combined treatments. Increasing our understanding of molecular integration of signals via allosteric receptor-receptor interactions in the heteroreceptor complexes will have a major impact on the molecular medicine, leading to novel strategies for drug discovery and treatment of diseases

On the Role of the Balance of GPCR Homo/ Heteroreceptor Complexes in the Brain

The early work on neuropeptide-monoamine receptor-receptor interactions in the Central Nervous System gave the first indications of the existence of G protein-coupled receptors (GPCRs) heteroreceptor complexes and the GPCR field began to expand from monomers into heteromers and higher order heteromers, including also GPCR-ion channel, Receptor Tyrosine Kinases (RTK)-GPCR and Receptor activity-modifying proteins-GPCR heteroreceptor complexes. The existence of heteroreceptor complexes with allosteric receptor-receptor interactions increases the diversity of receptor function including recognition, trafficking and signalling. We have proposed the molecular phenomenon of receptor-receptor interactions as a good way to understand of how brain function can increase through molecular integration of signals. An alteration in specific receptor-receptor interactions or their balance/equilibrium (with the corresponding monomers-homomers) are indeed considered to have a role in the pathogenic mechanisms that lead to various diseases, including drug addiction, depression, Parkinson's disease and schizophrenia. Therefore, targeting protomer-protomer interactions in heteroreceptor complexes or the balance with their corresponding homoreceptor complexes in discrete brain regions may become an important field for developing novel drugs, including heterobivalent drugs and optimal types of combined treatments. Increasing our understanding of molecular integration of signals via allosteric receptor-receptor interactions in the heteroreceptor complexes will have a major impact on the molecular medicine, leading to novel strategies for drug discovery and treatment of diseases

Consensus based recommendations for diagnosis and medical management of Poland syndrome (sequence)

Background Poland syndrome (OMIM: 173800) is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, breast, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals. Main body The aim of this work is to provide recommendations for the diagnosis and management of people affected by Poland syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years affected subjects. The literature search was performed in the second half of 2019. Original papers, meta-analyses, reviews, books and guidelines were reviewed and final recommendations were reached by consensus. Conclusion Being Poland syndrome a rare syndrome most recommendations here presented are good clinical practice based on the consensus of the participant experts

Association of MiR-126 with Soluble Mesothelin-Related Peptides, a Marker for Malignant Mesothelioma

BACKGROUND: Improved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress. METHODS AND RESULTS: miRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM. CONCLUSIONS AND SIGNIFICANCE: We propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos