CELL SORTING IN THE PRESENCE OF CYTOCHALASIN B

The ability of cytochalasin B to inhibit ruffled membrane activity and cellular locomotion of vertebrate cells in monolayer culture prompted its use to study the necessity for this kind of active cellular locomotion in cell sorting in heterotypic cell aggregates. Cell sorting was inhibited in chick embryo heart-pigmented retina aggregates but a remarkable degree of sorting did occur in neural retina-pigmented retina aggregates. In these experiments, the levels of cytochalasin B employed (5 or 10 µg/ml) are sufficient to inhibit completely locomotion of these cell types in monolayer culture. It is proposed that the degree of cell movement achieved during sorting in neural retina-pigmented retina aggregates in the presence of cytochalasin B is the result of changes in cell contact resulting from adhesive interaction of cells. The effect of cytochalasin B on the initial aggregation of dissociated cells was also tested. With the cell types used in this study (chick embryo neural retina and limb bud), aggregation was not affected for a period of several hours

Patient-reported outcome assessment of inflammatory arthritis patient experience with intravenously administered biologic therapy

Objective: To evaluate patient perspectives regarding utilization of intravenous (IV) therapy for inflammatory arthritis (IA). Methods: This was a single-center, non-interventional, patient questionnaire-based study of adult IA patients currently receiving IV biologics. At a single visit, patients completed the questionnaire comprising 30 questions centered on their experience receiving an intravenously administered therapy to treat their IA. The questionnaire included questions on patient demographics, disease characteristics, and previous biologic treatment for IA (subcutaneous [SC] and IV). Patients rated their level of agreement with statements regarding satisfaction with current IV biologic therapy and potential advantages and disadvantages of IV biologic therapy using a 5-point Likert scale (1= strongly disagree, 5= strongly agree). Results: One hundred patients were enrolled and completed the survey; 66% were female and the mean age was 58 years. Before IV treatment, 97% of patients received information regarding therapy options. Ninety patients ranked their satisfaction with current IV therapy as 4 or 5. The proportion of patients with an “extremely favorable” perception of IV therapy increased from 33% to 71% following initiation of their current medication. Thirty-one patients had previously received SC therapies to treat their IA. Conclusion: These results demonstrated an overall favorable perception of IV therapy among this patient population. Patients previously treated with SC therapy also had a positive shift in the perception of IV therapy after initiating IV therapy. Patients’ perception and preference for treatment options should be highly considered by the treating physician during or as part of a shared decision-making process. © 2017 Gaylis et al

On the nature of prominence emission observed by SDO/AIA

The Prominence-Corona Transition Region (PCTR) plays a key role in the thermal and pressure equilibrium of solar prominences. Our knowledge of this interface is limited and several major issues remain open, including the thermal structure and, in particular, the maximum temperature of the detectable plasma. The high signal-to-noise ratio of images obtained by the Atmospheric Imaging Assembly (AIA) on NASA's Solar Dynamics Observatory clearly show that prominences are often seen in emission in the 171 and 131 bands. We investigate the temperature sensitivity of these AIA bands for prominence observation, in order to infer the temperature content in an effort to explain the emission. Using the CHIANTI atomic database and previously determined prominence differential emission measure distributions, we build synthetic spectra to establish the main emission-line contributors in the AIA bands. We find that the Fe IX line always dominates the 171 band, even in the absence of plasma at > 10^6 K temperatures, while the 131 band is dominated by Fe VIII. We conclude that the PCTR has sufficient plasma emitting at > 4 10^5 K to be detected by AIA.Comment: accepted Ap

A techno-economic approach for decision-making in metal additive manufacturing: metal extrusion versus single and multiple laser powder bed fusion

This work presents a decision-making methodology that allows the merging of quantitative and qualitative decision variables for selecting the optimal metal Additive Manufacturing (AM) technology. The approach is applied on two competing technologies in the field of metal AM industry, i.e., the metal extrusion AM process (metal FFF) and the Laser Powder Bed Fusion process (LPBF) with single and multiple lasers, which represent the benchmark solution currently on the market. A comprehensive techno-economical comparison is presented where the two processes are analysed in terms of process capabilities (quality, easiness of use, setup time, range of possible materials, etc.) and costs, considering two different production scenarios and different parts’ geometries. In the first scenario, the AM system is assumed to be dedicated to one single part production while in this second scenario, the AM system is assumed to be saturated, as devoted to producing a wide mix of part types. For each scenario, two different part types made of 17–4 PH stainless steel are considered as a reference to investigate the effect of shape complexity, part size and production times to select the best technology when metal FFF and LPBF must be considered. The first part type refers to an extrusion die, to represent typical shapes of interest in the tooling industry, while the second part type is an impeller which can be used in many different industrial sectors, ranging from oil and gas to aerospace. In order to include quantitative and qualitative criteria, a decision-making model based on Analytic Hierarchy Process (AHP) is proposed as the enabler tool for decision making. The proposed approach allows to determine the most effective solution depending on the different production configurations and part types and can be used as a guideline and extended to include other technologies in the field of metal AM. On the other side, the critical discussion of the criteria selected, and the results achieved allow to highlight the pros and cons of the competing technologies, thus defining the existing limits to define directions for future research

Updated and new perspectives on diagnosis, prognosis, and therapy of malignant pheochromocytoma/paraganglioma.

Malignant pheochromocytomas/paragangliomas are rare tumors with a poor prognosis. Malignancy is diagnosed by the development of metastases as evidenced by recurrences in sites normally devoid of chromaffin tissue. Histopathological, biochemical, molecular and genetic markers offer only information on potential risk of metastatic spread. Large size, extraadrenal location, dopamine secretion, SDHB mutations, a PASS score higher than 6, a high Ki-67 index are indexes for potential malignancy. Metastases can be present at first diagnosis or occur years after primary surgery. Measurement of plasma and/or urinary metanephrine, normetanephrine and metoxytyramine are recommended for biochemical diagnosis. Anatomical and functional imaging using different radionuclides are necessary for localization of tumor and metastases. Metastatic pheochromocytomas/paragangliomas is incurable. When possible, surgical debulking of primary tumor is recommended as well as surgical or radiosurgical removal of metastases. I-131-MIBG radiotherapy is the treatment of choice although results are limited. Chemotherapy is reserved to more advanced disease stages. Recent genetic studies have highlighted the main pathways involved in pheochromocytomas/paragangliomas pathogenesis thus suggesting the use of targeted therapy which, nevertheless, has still to be validated. Large cooperative studies on tissue specimens and clinical trials in large cohorts of patients are necessary to achieve better therapeutic tools and improve patient prognosis

Performance evaluation of polymer-filled metal fused filament fabrication tooling for profile extrusion

The application of additive manufacturing (AM) for tooling in the mould and die industry brings a disruptive potential in process performance, design flexibility and product enhancements. Maturing of existing AM technologies and emerging technologies such as metal-fused filament fabrication (metal FFF) can further support the applicability of AM tooling in polymer profile extrusion. This study provides a complete characterization of metal FFF 17–4 PH stainless-steel die inserts and evaluates their applicability in a polymer extrusion process chain. The presented experimental assessment pivots on the metrological characterization of the produced inserts and the impact of the insert characteristics on the final extrudates’ product. Considering a conventionally manufactured benchmark insert, produced via subtractive methods (CNC machining and electrical discharge machining), comparable results for AM tools in terms of extrudates’ quality and process repeatability are presented. It was found that despite significant higher average surface parameters for AM insert tools (Sa = 2–9 μm vs. Sa = 0.3–0.9 μm for dies manufactured by machining), a much smaller difference was observed in the resulting quality of polymer extrudates’ product. The roughness generation effect of polymer profile extrusion based on the different dies’ internal surface roughness topography and the effect on extrudates product was evaluated. Three-dimensional average roughness Sa on acrylonitrile butadiene styrene extrudate surfaces obtained from conventionally machined dies was in the range of 0.3 μm. For extrudates obtained from additively manufactured dies, their Sa was in the rage of 0.5 μm (despite the much higher surface roughness of FFF dies compared to machined dies). The results confirm that with suitable extrudates’ product requirement, it is feasible to apply metal FFF as the selected manufacturing method for tooling in polymer profile extrusion

Understanding olive oil stability using filtration and high hydrostatic pressure

Veiled extra virgin olive oil (VEVOO) is very attractive on the global market. A study was performed to highlight the role of different amounts of water and microorganisms on the evolution of VEVOO quality during storage, using the selective effects of the application of individual or combined filtration and high hydrostatic pressure (HHP) treatments. Four oil processing trials were carried out in four replicates, resulting in a full factorial design with two independent fixed factors: filtration and HPP treatments. The turbidity of all the olive oil samples was characterized. Furthermore, all the olive oil samples were analysed for legal parameters, volatile organic compounds and phenolic compounds during the storage tests. The microbial contamination in the presence of a high level of water activity (>0.6 Aw) was related to the formation of volatile aroma compounds, which were responsible for the \u201cfusty\u201d sensory defect. Furthermore, high water activity values were related to an increase in the hydrolytic degradation rate of the phenolic compounds. The oil turbidity has to be planned and controlled, starting from adjustment of the water content and application of good manufacturing practices

Filtration scheduling: Quality changes in freshly produced virgin olive oil

Filtration is the most widespread stabilisation operation for extra virgin olive oil, preventing microbial and enzymatic changes. However, during the harvest, the workload of olive mills is at its peak. This results in two approaches to filtration: (i) delays it until after harvesting, increasing the risk of degraded oil quality, and (ii) filters it immediately, increasing the workload. The aim of our experiment is to assess the risk of delaying filtration and establish a safe delay time. Changes in the sensory profile and volatile compound contents were evaluated during 30 days in filtered and unfiltered samples. Significant differences were related to filtration: both turbidity grade and microbial contamination; no differences for the legal parameters were found. Two, contrasting, results were obtained with respect to oil quality: (i) the fusty defect, appearing in less than five days in unfiltered oils, leading to the downgrade of the oil\u2019s commercial category, and (ii) filtration removing some lipoxygenase volatile compounds. Consequently, a fruity attribute was more pronounced in unfiltered samples until day five of storage; it seems that, from this point, the fusty defect masked a fruity attribute. Hence, filtering within a few days strongly reduced the risk of degraded oil quality compared to a delayed filtration

Molecular analysis has allowed the definitive diagnosis of multiple acyl-CoA dehydrogenase deficiency (MADD)

Multiple acyl-CoA dehydrogenation deficiency (MADD) is a rare autosomal recessive disorder due to defects in the electron transfer flavoprotein (ETF) or in the electron transfer flavoprotein dehydrogenase (ETFDH) enzymes, involved in the mitochondrial electron transport chain. Patients with MADD fall into different clinical phenotypes, ranging from a severe neonatal presentation, with metabolic acidosis, cardiomyopathy and liver disease to a mild childhood/adult disease, with episodic metabolic decompensation, muscle weakness and respiratory failure.Nowadays, the MADD diagnosis is established by the presence of dicarboxylic organic acids and acylglycine derivatives in the urine and increased levels of medium-and long-chain acylcarnitines in the blood. Mutations in ETFA, ETFB, ETFDH genes, encoding for alpha and beta subunits of ETF and for ETF-dehydrogenase are associated with MADD. We report the case of a three years old child, affected by lethargy and asthenia associated with anorexia. Biochemical analyses showed hypoketotic hypoglycemia with remarkable increments in transaminases, lactic dehydrogenase, aldolase and creatine kinase. The chromatographic layout of urinary organic acids showed a typical dicarboxylic aciduria. Thus, based on these features, MADD was suspected. Fifteen years later, at the age of 19, MADD diagnosis was confirmed by molecular analysis, showing a compound heterozygosity for the mutations c.1074G>C (p.R358S; HGMD: CM031670 in HGMD database) and c.1073G>A (p.R358K) in the ETFDH gene. The c.1073G>A (p.R358K; rs796051959) mutation is reported in ClinVar database as pathogenic allele, although lacking link to a specific clinical condition. However, familial segregation study and in silico analysis, performed by bioinformatics tools, confirmed that this substitution is likely pathogenetic. Her parents were healthy carriers of one of the two mutations. It is known that the severity of the clinical phenotype of MADD may be related to the type of mutation in the ETFA/ETFB/ETFDH genes. Particularly, missense mutations in the ETFDH gene, leaving a detectable residual enzyme activity, may account for the milder form of the disease, as is the case here. In conclusion we suggest that molecular analysis is essential to the definitive diagnosis of MADD and to direct the adequate therapeutic management. Thus, through a close nutritional follow up, a few months ago the patient gave birth to a healthy boy. References Olsen et al. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat. 2003; 22:12–23