Prognostic Impact of a 3-MicroRNA Signature on Cytological Samples of Small-Cell Lung Cancer and on Surgical Samples of Squamous Cell Carcinoma of the Lung

Lung cancer is currently the most common malignancy and the leading cause of cancerrelated death worldwide. There are two main types: small cell lung cancer (SCLC) and nonsmall lung cancer (NSCLC). As revealed by recent genome-wide studies, individual lung tumors also possess highly diverse genomes, which further underscore the biological complexity of these diseases. Untangling the relationship between lung tumor histotype, phenotype and molecular heterogeneity represents a critical barrier in improving the clinical outcome of thoracic malignancies, which collectively account for most cancer-related deaths to date. Evidences from multiple tumour types and model systems implicate miRNA dysregulation as a common mechanism of tumorigenesis. Besides miRNAs are more stable than other biomarkers during sample processing, thus more suitable for analysis in tissue sample. Moreover, we have investigated whether the expression of a 3-miRNA panel could be a useful prognostic biomarker in lung cancer patients. The aims were the evaluation of the feasibility of miRNA extraction in cytological clinical (n= 50, SCLC) and surgical samples Squamous Cell Carcinoma (n=86; SCC) of lung, and the possible influence of the different types of fixative solution in the preservation of the integrity of miRNA. Moreover, we tried to identify a panel of miRNAs possibly useful in clinical practice as prognostic and /or predictive biomarkers. In SCLC, multivariate Cox analysis indicated that 3-miRNA panel was independently associated with survival, and in the group of older patients could discriminate patients with better survival from patients with short survival. In SCC Multivariate analysis indicated that in our cohort of patients with SCC, better OS and DSS are high expression levels of miR-192. In conclusion, the results obtained by our studies support the possibility of the use of selected miRNAs as prognostic biomarkers in cytologic and histologic clinical samples of lung tumours

A cryptic promoter in the first exon of the SPG4 gene directs the synthesis of the 60-kDa spastin isoform

<p>Abstract</p> <p>Background</p> <p>Mutations in <it>SPG4 </it>cause the most common form of autosomal dominant hereditary spastic paraplegia, a neurodegenerative disease characterized by weakness and spasticity of the lower limbs due to degeneration of the corticospinal tract. <it>SPG4 </it>encodes spastin, a microtubule-severing ATPase belonging to the AAA family. Two isoforms of spastin, 68 and 60 kDa, respectively, are variably abundant in tissues, show different subcellular localizations and interact with distinct molecules. The isoforms arise through alternative initiation of translation from two AUG codons in exon 1; however, it is unclear how regulation of their expression may be achieved.</p> <p>Results</p> <p>We present data that rule out the hypothesis that a cap-independent mechanism may be involved in the translation of the 60-kDa spastin isoform. Instead, we provide evidence for a complex transcriptional regulation of <it>SPG4 </it>that involves both a TATA-less ubiquitous promoter and a cryptic promoter in exon 1. The cryptic promoter covers the 5'-UTR and overlaps with the coding region of the gene. By using promoter-less constructs in various experimental settings, we found that the cryptic promoter is active in HeLa, HEK293 and motoneuronal NSC34 cells but not in SH-SY-5Y neuroblastoma cells. We showed that the cryptic promoter directs the synthesis of a <it>SPG4 </it>transcript that contains a shorter 5'-UTR and translates the 60-kDa spastin isoform selectively. Two polymorphisms (S44L and P45Q), leading to an early onset severe form of hereditary spastic paraplegia when present in heterozygosity with a mutant allele, fall a few nucleotides downstream of the novel transcriptional start site, opening up the possibility that they may exert their modifier effect at the transcriptional level. We provide evidence that at least one of them decreases the activity of the cryptic promoter in luciferase assays.</p> <p>Conclusion</p> <p>We identified a cryptic promoter in exon 1 of the <it>SPG4 </it>gene that selectively drives the expression of the 60-kDa spastin isoform in a tissue-regulated manner. These data may have implications for the understanding of the biology of spastin and the pathogenic basis of hereditary spastic paraplegia.</p

Long lasting allergic patch test reactions: a literature review

Long-lasting allergic patch test reactions (LLAPTR) are those in which the clinical features of palpable erythema are still present at the site of a positive allergic patch test reaction 14 or more days after application of the allergen. LLAPTR have been described for a wide range of contact allergens, many of these included in the baseline patch test series. LLAPTR are far from uncommon; they occur in consecutive patients with positive patch tests to baseline allergens with frequency up to 17.9% of the total reactions. Patch test reactions persisting for a very long time (up to several months after the test) have been described, the most frequent ones being those induced by gold salts. The pathomechanisms of LLAPTR have not been clarified, but may hypothetically involve a constant antigen stimulation and/or a defect in cell-mediated immunity down-regulation. Host-related factors significantly associated with LLAPTR are, according to some studies, a strong initial patch test response, older age, and atopy. No significant sex differences have been observed in the frequency of LLAPTR. </span

Clinicopathological features of an equine ovarian teratoma.

The present study describes the clinicopathological features of a mature cystic ovarian teratoma occurred in a 4 year old, cyclic, nulliparous Andalusian mare. The mass was discovered in the left ovary during a breeding soundness examination, and was hard in consistency and variously echogenic. Laparoscopy was performed to confirm the neoplastic change, followed by a unilateral laparotomic ovariectomy in the standing animal. On the cut surface the teratomatous ovary showed a large cyst filled with hair and sebaceous material and three small cysts containing mucous fluid, surrounded by solid areas where bone and cartilage could be recognized. Exceptionally, functional remnants of the ovary, including small follicles and a diestral corpus luteum were found near the tubal extremity. Histology revealed mature tissues foreign to the ovary including stratified squamous and respiratory epithelia, mucous, sebaceous and sweat glands, muscle fibres, fat and nervous tissue. The appearance of tracheal and lung architecture was occasionally observed

Effects of hydrodynamic cavitation, low-level thermal and low-level alkaline pre-treatments on sludge solubilisation.

Abstract WAS is a polluting and hazardous waste generated in WWTPs that must be treated to prevent pollution and human health risks. Anaerobic digestion is the most used process for sludge stabilization. However, it must be improved in terms of both speed and extend of degradation. With the purpose of reducing the energy and chemical consumption linked to sludge treatment, in this study, different anaerobic digestion pre-treatments such as low-level mechanical (hydrodynamic cavitation, 2 bar), low-level thermal (50 °C) and low-level alkaline (NaOH, KOH and Ca(OH)2, pH 10) methods, and a combination thereof, were tested as strategies to improve sludge solubilisation. When the pre-treatments were used alone, the alkaline pre-treatment showed the highest sludge solubilisation. Among the alkaline reagents tested, NaOH and KOH led to higher DDPCOD (41.6 and 39.4%), while only 8.4% was achieved by using Ca(OH)2. However, the low-level hydrodynamic cavitation assisted thermo-alkaline pre-treatment was the most efficient in terms of both sludge solubilisation (DDPCOD = 53.0%) and energy efficiency (EE = 64.5 mgΔSCOD kJ−1). The synergetic effects of the combined pre-treatment were also confirmed by the highest release of EPS. Furthermore, cytometric analyses showed that the main mechanism involved in sludge solubilisation for the investigated pre-treatments was flocs disintegration rather than cell lysis

Effects of design and operational conditions on performance of constructed wetlands for agricultural pollution control - critical review

Constructed wetlands (CWs) can be considered as an efficient nature-based solution for treatment of agricultural drainage water (ADW) and consequently for the mitigation of the non-point source pollution. Aiming to provide suggestions for the construction and implementation of CWs, this paper proposes and discusses key parameters of CW design and operation. In order to verify the effect of these features, different case studies were reviewed, focusing on the performance of CWs that are treating agricultural drainage water. The findings showed that design and operational factors (e.g., the application of simple hydraulic structures and vegetation establishment) can improve the pollutant removal efficiencies by increasing hydraulic retention time. Hydraulic efficiency of CWs can also be enhanced through certain shape characteristics (e.g., adoption of a high aspect ratio, creation a long and narrow CW shape). The careful consideration of these parameters before and during CW implementation can therefore help these systems to achieve their full potential. However, further study is recommended to assess effects of some parameters (e.g., flow direction and the application of deep zones)

Assessing mental health therapeutic communities functioning

Empirical and clinical evidence shows that therapeutic communities produce changes in people’s mental health and well-being. Treatment in communities has effects on improving interpersonal relationships, acceptance among members, ability to recognize other people’s feelings, symptomatology, life satisfaction and self-esteem. This paper aims to investigate which factors can explain the treatment effectiveness, measured by an index which incorporates the point of view of the communities staff members, by means of a beta regression model with random intercept. The results show the influence of some organizational dimension as well as staff roles, providing a meaningful insights into the functioning of mental therapeutic communities with implications of particular interest to the mental health sector stakeholders

Neonatal Hypersusceptibility to Endotoxin Correlates with Increased Tumor Necrosis Factor Production in Mice

Septic shock is a major cause of mortality in neonates. The hypothesis was tested that neonatal, age is associated with altered sensitivity to shock-inducing bacterial products or proinflammatory, cytokines (or both). Mice of different ages were inoculated with various doses of lipopolysaccharide, (LPS), superantigenic staphylococcal enterotoxin B (SEB), or recombinant tumor necrosis factor-α, (rTNF-α), alone or in combination with the sensitizing agent D-galactosamine. Neonatal mice were, markedly more susceptible to LPS-induced lethality but more resistant to SEB than were adults (P, \u3c .05). Mice of different ages did not differ, however, in their sensitivity to lethal activities of rTNFα. Neonatal susceptibility to LPS and SEB correlated directly with plasma TNF-α but not IFN-γ, levels, which was confirmed by TNF-α and IFN-γ blockade experiments. These data document, marked age-related differences in the pathophysiology of septic shock and suggest that IFN-γ is, not an obligatory mediator of either LPS- or SEB-induced lethality in neonates