The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.     

Soil-washing design methodology for a lead-contaminated sandy-soil

Soils located near high traffic roadways, particularly where renovations have taken place, typically exhibit elevated levels of trace metals in the upper soil horizon. Regulators are currently seeking an efficient method of site characterization and treatment system design which will lend itself to timely and environmentally efficacious clean-up. The soil investigated in this study was a silty sand collected near a bridge abutment for a major interstate highway. The soil had a total lead content of 1392 mg/kg. In addition, the soil contained a considerable fraction of organic carbon (approximately 6.3%). A sequential chemical extraction indicated that a fraction of contaminants were in labile soil phases and thus amenable to chemical extraction (soil-washing). A soil washing design methodology is presented based on surface chemistry and equilibrium stage operation. In this work, a double layer surface complexation model was used to describe equilibrium sorption behavior and a preliminary design of an ex-situ counter-current equilibrium stage extraction process is presented. Model calibration was conducted using sorption data obtained from a 1:40 solid to liquid ratio (s/l), adsorption edge. Model validation was accomplished with batch titration data and a 1:20 s/l, adsorption edge. The model accurately predicted leachable lead concentrations over a wide pH range. The required number of ideal equilibrium stages was highly sensitive to pH.     

Diabetes and Ischemic Stroke: An Old and New Relationship an Overview of the Close Interaction between These Diseases

Diabetes mellitus is a comprehensive expression to identify a condition of chronic hyperglycemia whose causes derive from different metabolic disorders characterized by altered insulin secretion or faulty insulin effect on its targets or often both mechanisms. Diabetes and atherosclerosis are, from the point of view of cardio- and cerebrovascular risk, two complementary diseases. Beyond shared aspects such as inflammation and oxidative stress, there are multiple molecular mechanisms by which they feed off each other: chronic hyperglycemia and advanced glycosylation end-products (AGE) promote ‘accelerated atherosclerosis’ through the induction of endothelial damage and cellular dysfunction. These diseases impact the vascular system and, therefore, the risk of developing cardio- and cerebrovascular events is now evident, but the observation of this significant correlation has its roots in past decades. Cerebrovascular complications make diabetic patients 2–6 times more susceptible to a stroke event and this risk is magnified in younger individuals and in patients with hypertension and complications in other vascular beds. In addition, when patients with diabetes and hyperglycemia experience an acute ischemic stroke, they are more likely to die or be severely disabled and less likely to benefit from the one FDA-approved therapy, intravenous tissue plasminogen activator. Experimental stroke models have revealed that chronic hyperglycemia leads to deficits in cerebrovascular structure and function that may explain some of the clinical observations. Increased edema, neovascularization, and protease expression as well as altered vascular reactivity and tone may be involved and point to potential therapeutic targets. Further study is needed to fully understand this complex disease state and the breadth of its manifestation in the cerebrovasculature.     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Detection of frozen salt in pipes using gamma-ray spectrometry of potassium self-activity

Solar plants that use molten salts as heat transfer fluid need careful control to avoid the freezing of the salt in the pipes; if such a problem occurs, a diagnostic instrument to localize where is the frozen salt plug and to determine its length is useful. If the salt contains potassium (as is the case of the most common mixture used in solar plants, NaNO₃/KNO₃ 60/40% by weight), the gamma decay of the natural unstable isotope ⁴⁰K can be exploited to detect the frozen salt in a non-invasive way. Simulations and experimental results regarding the detectability of such plugs with different masses/lengths are presented.     

Experimental study on the restart of core-annular flow

We show the results of an experimental campaign to study the pressure drop during the restart of a core-annular flow from a stratified configuration. In normal core annular flow operations, due to fouling or pump failures, a core flow may not be sustained anymore and hence it stratifies. Since the pressure drops connected to the stratified flow regime are much larger than the ones of core annular, the flow suddenly stops. To restart it there are two possibilities: one is to try to provide a higher pressure gradient trying to restore the flow of water and oil, the other is to clean the pipe using water only: in both cases an attachment of a thin layer of oil on the pipe internal wall occurs and the pressure drop for water only or oil–water are higher than the previous ones with clean pipe wall. We focused our attention on the cleaning by water only and we provide experimental data on the evolution of the pressure drop as function of time in order to find when the pipe could be considered as perfectly cleaned or, at least, when the pressure drop are low enough to restart the oil flow. The experimental results are finally compared with a two-fluid model available in literature.