On the simulation,economic analysis,and life cycle assessment of batch-mode organic solvent recovery alternatives for the pharmaceutical industry

This study explores design alternatives for the purification and possible reuse of low-volume organic solvents waste streams in pharmaceutical manufacturing. Solvent use has a large impact on the life cycle of pharmaceutical processes, as typically 80–90% of the total mass used in the production of an active pharmaceutical ingredient is attributed to solvent use. Solvents are not consumed in pharmaceutical processes so they exit the process as waste. These waste streams are usually disposed of using incineration; therefore, generating significant life cycle emissions from disposal and replacement of virgin solvent. Solvent recovery efforts are generally limited to large-volume waste streams. However, results show that solvents in low-volume streams can also be economically recovered using a versatile multi-campaign solvent recovery skid. Three different solvent waste streams were evaluated, and 85.3% reduction in total emissions and 86.3% reduction in operating costs were achieved. Investment in the solvent recovery system was determined to have a payback period of 4.5 years and a 28% IRR over 10 years. A life cycle impact assessment shows impacts on the human health, ecosystems, and resources categories have been reduced by 82.4, 85.1, and 87.1%, respectively.     

A numerical modelling for the extraction of decay regions from color images of monuments

An innovative application focused on the segmentation of decay zones from images of stone materials is presented. The adopted numerical approach to extract decay regions from the color images of monuments provides a tool that helps experts analyze degraded regions by contouring them. In this way even if the results of the proposed procedure depend on the evaluation of experts, the approach can be a contribution to improving the efficiency of the boundary detection process. The segmentation is a process that allows an image to be divided into disjoint zones so that partitioned zones contain homogeneous characteristics. The numerical method, used to segment color images, is based on the theory of interface evolution, which is described by the eikonal equation. We adopted the fast marching technique to solve the upwind finite difference approximation of the eikonal equation. The fast marching starts from a seed point in the region of interest and generates a front which evolves according to a specific speed function until the boundary of the region is identified. We describe the segmentation results obtained with two speed functions, attained by the image gradient computation and color information about the object of interest. Moreover, we present the extension of the working modality of the method by introducing the possibility to extract the regions not only in a local way but also in a global way on the entire image. In this case, in order to improve the segmentation efficiency the application of the fast marching technique starts with more seed points defined as seed regions. The study case concerns the impressive remains of the Roman Theatre in the city of Aosta (Italy). In the image segmentation process the color space L^∗a^∗b^∗$L^{\ast }{a}^{\ast }{b}^{\ast }$ is utilized.     

Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence that includes FP-RMS, harboring the fusion oncoprotein PAX3/7-FOXO1 and FN-RMS, often mutant in the RAS pathway. Risk stratifications of RMS patients determine different prognostic groups and related therapeutic treatment. Current multimodal therapeutic strategies involve surgery, chemotherapy (CHT) and radiotherapy (RT), but despite the deeper knowledge of response mechanisms underpinning CHT treatment and the technological improvements that characterize RT, local failures and recurrence frequently occur. This review sums up the RMS classification and the management of RMS patients, with special attention to RT treatment and possible radiosensitizing strategies for RMS tumors. Indeed, RMS radioresistance is a clinical problem and further studies aimed at dissecting radioresistant molecular mechanisms are needed to identify specific targets to hit, thus improving RT-induced cytotoxicity.     

Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism

Obesity is a chronic illness associated with several metabolic derangements and comorbidities (i.e., insulin resistance, leptin resistance, diabetes, etc.) and often leads to impaired testicular function and male subfertility. Several mechanisms may indeed negatively affect the hypothalamic–pituitary–gonadal health, such as higher testosterone conversion to estradiol by aromatase activity in the adipose tissue, increased ROS production, and the release of several endocrine molecules affecting the hypothalamus–pituitary–testis axis by both direct and indirect mechanisms. In addition, androgen deficiency could further accelerate adipose tissue expansion and therefore exacerbate obesity, which in turn enhances hypogonadism, thus inducing a vicious cycle. Based on these considerations, we propose an overview on the relationship of adipose tissue dysfunction and male hypogonadism, highlighting the main biological pathways involved and the current therapeutic options to counteract this condition.     

Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma

Patients with advanced thyroid cancer harboring NTRK rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for NTRK rearrangements, but its efficacy has been poorly explored in thyroid cancer. The aim of this study is to investigate the diagnostic utility of Trk IHC in the identification of NTRK rearrangements. A series of 26 follicular-derived thyroid tumors, positive for NTRK rearrangements, and 28 NTRK fusion-negative controls were retrospectively analyzed by IHC using the pan-Trk monoclonal antibody (clone {"type":"entrez-protein","attrs":{"text":"EPR17341","term_id":"523383444","term_text":"EPR17341"}}EPR17341) on the Ventana system. Area under the curve (AUC), sensitivity and specificity were calculated by ROC analysis. Trk expression was detected in 25 samples, including 22 out of the 26 NTRK-rearranged (84.6%) and three out of 28 NTRK-negative samples (10.7%). Four out of twenty-six NTRK-rearranged thyroid tumors were negative for Trk expression (15.4%), all carrying the ETV6/NTRK3 fusion. The AUC, sensitivity and specificity were 0.87, 0.85 and 0.89, respectively. A screening based on IHC analysis showed limited sensitivity and specificity in the identification of NTRK-rearranged tumors. Since falsely negative results could preclude the administration of effective targeted drugs, alternative detection strategies should be considered for thyroid cancer.     

Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling,reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats

Dietary PUFA, mainly those of the n‐3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low‐fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso‐energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF‐α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione‐S‐transferase NADH quinone oxidoreductase) in DM‐treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid‐related factor 2 pathway.     

Obesity and Male Reproduction: Do Sirtuins Play a Role?

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.     

The effect of compatibilization on the behavior of a polycarbonate/polymer liquid crystal blend

Polymer liquid crystalline materials (PLC) blended with engineering plastics (EP) have the potential to reduce viscosity and increase the modulus of the EP, particularly if the PLC is in a favorable fibrillar morphology. A major deficiency in these blends—as with many other immiscible polymeric systems—is poor failure properties. In this paper, polycarbonate (PC) and a rigid, all-aromatic commercial PLC are blended and a third resin, a copolymer of methyl methacrylate and N-methyl-dimethyl-glutarimide is included as a compatibilizing agent. Characterization of the binary and ternary blends is carried out using rheological, mechanical, morphological, and dynamic mechanical characterization techniques. Binary blends of PLC in a PC matrix result in an immiscible, nodular morphology with low failure stresses. The addition of the copolymeric compatibilizer—particularly one with reactive functionalities—is found to improve tensile strength and yield a fibrillar blend morphology. It is proposed that this may be due to the compatibilizer reducing interfacial tension and adhering to the blend phases, rather than by causing a major change in blend viscosity.     

Complete Characterization of the O-Antigen from the LPS of Aeromonas bivalvium

Aeromonas species are found in the aquatic environment, drinking water, bottled mineral water, and different types of foods, such as meat, fish, seafood, or vegetables. Some of these species are primary or opportunistic pathogens for invertebrates and vertebrates, including humans. Among the pathogenic factors associated with these species, there are the lipopolysaccharides (LPSs). LPSs are the major components of the external leaflet of Gram-negative bacterial outer membrane. LPS is a glycoconjugate, generally composed of three portions: lipid A, core oligosaccharide, and O-specific polysaccharide or O-antigen. The latter, which may be present (smooth LPS) or not (rough LPS), is the most exposed part of the LPS and is involved in the pathogenicity by protecting infecting bacteria from serum complement killing and phagocytosis. The O-antigen is a polymer of repeating oligosaccharide units with high structural variability, particularly the terminal sugar, that confers the immunological specificity to the O-antigen. In this study, we established the structure of the O-chain repeating unit of the LPS from Aeromonas bivalvium strain 868 E^T (=CECT 7113^T = LMG 23376^T), a mesophilic bacterium isolated from cockles (Cardium sp.) and obtained from a retail market in Barcelona (Spain), whose biosynthesis core LPS cluster does not contain the waaE gene as most of Aeromonas species. After mild acid hydrolysis, the lipid A was removed by centrifugation and the obtained polysaccharide was fully characterized by chemical analysis and NMR spectroscopy. The polymer consists of a heptasaccharide repeating unit containing D-GalNAc, L-Rha, D-GlcNAc, and D-FucNAc residues.