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.     

Artificial Intelligence Technologies for COVID-19 De Novo Drug Design

The recent covid crisis has provided important lessons for academia and industry regarding digital reorganization. Among the fascinating lessons from these times is the huge potential of data analytics and artificial intelligence. The crisis exponentially accelerated the adoption of analytics and artificial intelligence, and this momentum is predicted to continue into the 2020s and beyond. Drug development is a costly and time-consuming business, and only a minority of approved drugs generate returns exceeding the research and development costs. As a result, there is a huge drive to make drug discovery cheaper and faster. With modern algorithms and hardware, it is not too surprising that the new technologies of artificial intelligence and other computational simulation tools can help drug developers. In only two years of covid research, many novel molecules have been designed/identified using artificial intelligence methods with astonishing results in terms of time and effectiveness. This paper reviews the most significant research on artificial intelligence in de novo drug design for COVID-19 pharmaceutical research.     

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.     

A Review of Guidance Approaches in Visual Data Analysis: A Multifocal Perspective

Visual data analysis can be envisioned as a collaboration of the user and the computational system with the aim of completing a given task. Pursuing an effective system‐user integration, in which the system actively helps the user to reach his/her analysis goal has been focus of visualization research for quite some time. However, this problem is still largely unsolved. As a result, users might be overwhelmed by powerful but complex visual analysis systems which also limits their ability to produce insightful results. In this context, guidance is a promising step towards enabling an effective mixed‐initiative collaboration to promote the visual analysis. However, the way how guidance should be put into practice is still to be unravelled. Thus, we conducted a comprehensive literature research and provide an overview of how guidance is tackled by different approaches in visual analysis systems. We distinguish between guidance that is provided by the system to support the user, and guidance that is provided by the user to support the system. By identifying open problems, we highlight promising research directions and point to missing factors that are needed to enable the envisioned human‐computer collaboration, and thus, promote a more effective visual data analysis.     

New processes in the environmental chemistry of nitrite. 2. The role of hydrogen peroxide

The oxidation of nitrite and nitrous acid to *NO2 upon irradiation of dissolved Fe(III), ferric (hydr)oxides, and nitrate has previously been shown to enhance phenol nitration. This allowed the proposal of a new role for nitrite and nitrous acid in natural waters and atmospheric aerosols. This paper deals with the interaction between hydrogen peroxide, a key environmental factor in atmospheric oxidative chemistry, and nitrite/nitrous acid. The reaction between nitrous acid and hydrogen peroxide yields peroxynitrous acid, a powerful nitrating agent and an important intermediate in atmospheric chemistry. The kinetics of this reaction is compatible with a rate-determining step involving either H3O2+ and HNO2 or H2O2 and protonated nitrous acid. In the former case the rate constant between the two species would be 179.6 +/- 1.4 M(-1) s(-1), in the latter case it would be as high as (1.68 +/- 0.01) x 10(10) M(-1) s(-1) (diffusion-controlled reaction). Due to the more reasonable value of the rate constant, the reaction between H3O2+ and HNO2 seems more likely. In the presence of HNO2 + H2O2 the nitration of phenol is strongly enhanced when compared with HNO2 alone. The nitration rate of phenol in the presence of peroxynitrous acid decreases as pH increases, thus HOONO is a potential source of atmospheric nitroaromatic compounds in acidic water droplets. The mixture Fe(II) + H2O2 (Fenton reagent) can oxidize nitrite and nitrous acid to nitrogen dioxide, which results in phenol nitration. The nitration in the presence of Fe(II) + H2O2 + NO2-/HNO2 occurs more rapidly than the one with H2O2 + NO2-/HNO2 at pH 5, where little HNO2 is available to directly react with hydrogen peroxide. Both systems, however, are more effective than NO2-/HNO2 alone in producing nitrophenols from phenol. Another process leading to the oxidation of nitrite to nitrogen dioxide is the photo-Fenton one. It can be relevant at pH > or = 6, as nitrite does not react with H2O2 at room temperature. Under such conditions the source of Fe(II) is the photolysis of ferric (hydr)oxides (heterogeneous photo-Fenton reaction). In the presence of nitrite this reaction induces very effective nitrophenol formation from phenol.     

Laccase Mediator Cocktail System as a Sustainable Skin Whitening Agent for Deep Eumelanin Decolorization

The overproduction of eumelanin leads to a panel of unaesthetic hyper-pigmented skin diseases, including melasma and age spots. The treatment of these diseases often requires the use of tyrosinase inhibitors, which act as skin whitening agents by inhibiting the synthesis of eumelanin, with harmful side effects. We report here that laccase from Trametes versicolor in association with a cocktail of natural phenol redox mediators efficiently degraded eumelanin from Sepia officinalis, offering an alternative procedure to traditional whitening agents. Redox mediators showed a synergistic effect with respect to their single-mediator counterpart, highlighting the beneficial role of the cocktail system. The pro-oxidant DHICA sub-units of eumelanin were degraded better than the DHI counterpart, as monitored by the formation of pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA) degradation products. The most effective laccase-mediated cocktail system was successively applied in a two-component prototype of a topical whitening cream, showing high degradative efficacy against eumelanin.     

Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1–9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.     

Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients

The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.