Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases

The skin is the largest organ of the human body, serving as an effective mechanical barrier between the internal milieu and the external environment. The skin is widely considered the first-line defence of the body, with an essential function in rejecting pathogens and preventing mechanical, chemical, and physical damages. Keratinocytes are the predominant cells of the outer skin layer, the epidermis, which acts as a mechanical and water-permeability barrier. The epidermis is a permanently renewed tissue where undifferentiated keratinocytes located at the basal layer proliferate and migrate to the overlying layers. During this migration process, keratinocytes undertake a differentiation program known as keratinization process. Dysregulation of this differentiation process can result in a series of skin disorders. In this context, aquaporins (AQPs), a family of membrane channel proteins allowing the movement of water and small neutral solutes, are emerging as important players in skin physiology and skin diseases. Here, we review the role of AQPs in skin keratinization, hydration, keratinocytes proliferation, water retention, barrier repair, wound healing, and immune response activation. We also discuss the dysregulated involvement of AQPs in some common inflammatory dermatological diseases characterised by skin barrier disruption.     

Pathogenetic Mechanisms of Hypertension–Brain-Induced Complications: Focus on Molecular Mediators

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.     

Experimental study on condensation heat transfer inside a single circular minichannel

The measurement of the condensation heat transfer coefficient inside micro- and minichannels is still somewhat elusive due to the difficult task of getting accurate values of the heat transfer coefficients during the condensation process, particularly when studied within single minichannels. The present paper reports local heat transfer coefficients obtained from the measurement of the local heat flux and the direct measurement of the saturation and wall temperatures during condensation of R134a and R32 within a single circular 0.96 mm diameter minichannel. Except for the lowest mass velocity, the test results do not show significant discrepancy from the trends expected for macroscale tubes.     

Optimal design of an integrated renewable-storage energy system in a mixed-use building

The rise of mixed-use buildings contributes to the sustainable development of cities but are still met with challenges in energy management due to the lack of energy efficiency and sustainability guidelines. The use of integrated renewable-storage energy systems is a more beneficial solution to this problem over individual solutions; however, most design studies only focused on single-type buildings. Thus, this study aims to optimally design an integrated energy system for mixed-use buildings using HOMER Grid. The objective is to minimize the net present costs, subject to capacity limits, energy balances, and operational constraints. Economic metrics were used to evaluate and compare the proposed system to the varying design cases such as business-as-usual, stand-alone renewable source, and stand-alone energy storage. The case study considered a mixed-use building in a tropical area, with a solar photovoltaic system as the renewable energy source and lithium-ion battery as the energy storage system technology. The results show that the integrated system is the most financially attractive design case. It has a levelized cost of electricity of 0.1384 US$ kWh⁻¹, which is significantly less than the 0.2580 US$ kWh⁻¹ baseline. The system also provides electricity cost savings of 294 698 US$ y⁻¹, excess electricity of 35 746 kWh, and carbon emission reduction of 550 tons annually for a mixed-use building with daily average consumption of 4557-kWh and 763-kW peak demand.     

A glucose-specific metric to assess predictors and identify models

In diabetes, the mean square error (MSE) metric is extensively used for assessing glucose prediction methods and identifying glucose models. One limitation of this metric is that, by equally treating errors in hypo-, eu-, and hyperglycemia, it is not able to weight the different clinical impact of errors in these three situations. In this paper, we propose a new cost function, which overcomes this limitation and can be used in place of MSE for several scopes, in particular for assessing the quality of glucose predictors and identifying glucose models. The new metric called glucose-specific MSE (gMSE) modifies MSE with a Clark error grid inspired penalty function, which penalizes overestimation in hypoglycemia and underestimation in hyperglycemia, i.e., the most harmful conditions on a clinical perspective. From a mathematical point of view, gMSE retains sensitivity of MSE and inherits some of its important mathematical features, in particular it has no local minima, simplifying the optimization. This makes it suitable for model identification purposes also. First, the goodness of it is demonstrated by means of three experiments, designed ad hoc to evidence its sensitivity to accuracy, precision, and distortion in glucose predictions. Second, a prediction assessment problem is presented, in which two real prediction profiles are compared. Results show that the MSE chooses the worst clinical situation, while gMSE correctly selects the situation with less clinical risk. Finally, we also demonstrate that models identified minimizing gMSE are more accurate in potentially harmful situations (hypo- and hyperglycemia) than those obtained by MSE.     

Leonardo da Vinci: the search for the soul

The human race has always contemplated the question of the anatomical location of the soul. During the Renaissance the controversy crystallized into those individuals who supported the heart ("cardiocentric soul") and others who supported the brain ("cephalocentric soul") as the abode for this elusive entity. Leonardo da Vinci (1452-1519) joined a long list of other explorers in the "search for the soul." The method he used to resolve this anatomical problem involved the accumulation of information from ancient and contemporary sources, careful notetaking, discussions with acknowledged experts, and his own personal search for the truth. Leonardo used a myriad of innovative methods acquired from his knowledge of painting, sculpture, and architecture to define more clearly the site of the "senso comune"--the soul. In this review the author examines the sources of this ancient question, the knowledge base tapped by Leonardo for his personal search for the soul, and the views of key individuals who followed him.