Neuroprotective Effects of Testosterone in the Hypothalamus of an Animal Model of Metabolic Syndrome

Metabolic syndrome (MetS) is known to be associated to inflammation and alteration in the hypothalamus, a brain region implicated in the control of several physiological functions, including energy homeostasis and reproduction. Previous studies demonstrated the beneficial effects of testosterone treatment (TTh) in counteracting some MetS symptoms in both animal models and clinical studies. This study investigated the effect of TTh (30 mg/kg/week for 12 weeks) on the hypothalamus in a high-fat diet (HFD)-induced animal model of MetS, utilizing quantitative RT-PCR and immunohistochemical analyses. The animal model recapitulates the human MetS features, including low testosterone/gonadotropin plasma levels. TTh significantly improved MetS-induced hypertension, visceral adipose tissue accumulation, and glucose homeostasis derangements. Within hypothalamus, TTh significantly counteracted HFD-induced inflammation, as detected in terms of expression of inflammatory markers and microglial activation. Moreover, TTh remarkably reverted the HFD-associated alterations in the expression of important regulators of energy status and reproduction, such as the melanocortin and the GnRH-controlling network. Our results suggest that TTh may exert neuroprotective effects on the HFD-related hypothalamic alterations, with positive outcomes on the circuits implicated in the control of energy metabolism and reproductive tasks, thus supporting a possible role of TTh in the clinical management of MetS.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Hydrocarbon condensation modelling to mitigate fluid coker cyclone fouling

FLUID COKING is a continuous process that thermally converts heavy hydrocarbons, such as oil sands bitumen, to lighter and higher‐value products by horizontal spray injection onto a fluidized bed of hot coke particles. The cyclone sections of commercial fluid coker reactors experience fouling during typical operation, which limits unit run lengths. The main objective of this work is to improve fluid coker reliability by proposing cyclone fouling mitigation strategies based on practical operation modifications. This study developed a process simulation in Aspen Plus to establish the combined impact of vapour‐liquid equilibrium, endothermic thermal cracking reactions, pressure changes, and overall fluid dynamics in the selected fluid coker control volumes. The hydrocarbon composition was defined by applying an assay characterization of distillation data for representative hydrocarbon streams. Case studies were performed to determine the sensitivity of the predicted temperatures and hydrocarbon condensate flow rates for: (a) the burner‐to‐fluid coker transfer line temperature; (b) the hot coke flow rate; (c) hot coke entrainment from the freeboard region; and (d) scouring coke flow rate in the horn chamber. The scouring coke flow rate was identified as the most promising process lever to mitigate fluid coker cyclone fouling.     

On‐Chip Magnetic Platform for Single‐Particle Manipulation with Integrated Electrical Feedback

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high‐throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig‐zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1‐μm sized beads is demonstrated.     

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.     

A microfluidic approach for development of hybrid collagen-chitosan extracellular matrix-like membranes for on-chip cell cultures

To advance organ-on-a-chip development and other areas befitting from physiologically-relevant biomembranes,a microfluidic platform is presented for synthesis of biomembranes during gelation and investigation into their role as extracellular matrix supports.In this work,high-throughput studies of collagen,chitosan,and collagen-chitosan hybrid biomembranes were carried out to characterize and compare key properties as a function of the applied hydrodynamic conditions during gelation.Specifically,depending on the biopolymer material used,varying flow conditions during biomembrane gelation caused width,uniformity,and swelling ratio to be differently affected and controllable.Finally,cell viability studies of seeded fibroblasts were conducted,thus showing the potential for biological applications.     

Solid Fat Content as a Substitute for Total Polar Compound Analysis in Edible Oils

The solid fat contents (SFC) of heated edible oil samples were measured and found to correlate positively with total polar compounds (TPC) and inversely with triglyceride concentration. Traditional methods for determination of TPC require a laboratory setting and are time and solvent intensive. Therefore, SFC analysis represents a viable user-friendly alternative to measuring total polar components in environments where low-resolution NMR may already be in use, for example, in quality assurance environments. The slope of SFC measurements versus time was also found to correlate with the oxidative stability index of the edible oils studied.     

The Composition of Mixed Micelles Formed by Dodecyl Trimethyl Ammonium Bromide and Benzethonium Chloride in Water

The composition of the mixed micelles formed by benzethonium chloride and dodecyl trimethyl ammonium bromide in water were experimentally determined by a combination of surfactant ion-selective electrodes and UV–Vis spectroscopy measurements. Results were compared with the computed compositions from three theories on mixed micelles available in the literature (Regular Solution, Motomura’ and Georgiev’s). The basis of the Junquera and Aicart method and the determination of the micelle aggregation number (N) by pyrene fluorescence quenching, i.e., the constancy of N and the mixed micelle composition when the total concentration is changed, were not supported by our experimental results. Experimental micelle compositions were statistically equal to those computed by Regular Solution Theory. The mixed micelle composition and the quantity of non-micellized surfactant molecules change with concentration above the critical micelle concentration, and therefore do not support the assumptions used in the Junquera and Aicart procedure and in the determination of N by pyrene fluorescence quenching. The reason why the latter procedure gives N values similar to those obtained from other techniques is discussed.     

The magnitude of a product recall: offshore outsourcing vs. captive offshoring effects

The escalation in product recalls in recent years is attributed to the rise of globalisation and associated challenges of offshoring. Extant SCM research suggests that product recalls have a significant negative impact on financial performance, but gaps exist relative to the managerial actions to minimise their impact. Recall response strategies have become more important in the press, given that a single recall may result in the mandatory withdrawal of millions of products from the market, with firms incurring enormous logistics costs and brand damage. In this study, we address this gap in the research, and using a measure of product recall defined as the volume of products withdrawn from the market due to product quality failure. We explore the scale of the recall in the context of pharmaceutical sector global sourcing strategies, exploring whether the variation in global sourcing decisions not only increases the likelihood of a recall, but also influences the capability to minimise the total cost of recall. Our results suggest that offshore outsourcing and captive offshoring have opposite effects in terms of their influence on the magnitude of product recall. We summarise the implications through a compelling set of insights for future global sourcing strategy research themes.