Specific Local Predictors That Reflect the Tropism of Endometriosis—A Multiple Immunohistochemistry Technique

Ectopic endometrial epithelium associates a wide spectrum of symptomatology. Their evolution can be influenced by inflammatory and vascular changes, that affect not only the structure and cell proliferation rate, but also symptoms. This prospective study involved tissue samples from surgically treated patients, stained using classical histotechniques and immunohistochemistry. We assessed ectopic endometrial glands (CK7+, CK20−), adjacent blood vessels (CD34+), estrogen/progesterone hormone receptors (ER+, PR+), inflammatory cells (CD3+, CD20+, CD68+, Tryptase+), rate of inflammatory cells (Ki67+) and oncoproteins (BCL2+, PTEN+, p53+) involved in the development of endometriosis/adenomyosis. A CK7+/CK20− expression profile was present in the ectopic epithelium and differentiated it from digestive metastases. ER+/PR+ were present in all cases analyzed. We found an increased vascularity (CD34+) in the areas with abdominal endometriosis and CD3+−:T-lymphocytes, CD20+−:B-lymphocytes, CD68+:macrophages, and Tryptase+: mastocytes were abundant, especially in cases with adenomyosis as a marker of proinflammatory microenvironment. In addition, we found a significantly higher division index-(Ki67+) in the areas with adenomyosis, and inactivation of tumor suppressor genes-p53+ in areas with neoplastic changes. The inflammatory/vascular/hormonal mechanisms trigger endometriosis progression and neoplastic changes increasing local pain. Furthermore, they may represent future therapeutic targets. Simultaneous-multiple immunohistochemical labelling represents a valuable technique for rapidly detecting cellular features that facilitate comparative analysis of the studied predictors.     

Can porous polymeric scaffolds be functionalized by stem cells leading to osteogenic differentiation? A systematic review of in vitro studies

The aim of this study was to analyze the influence of nanoporous structure of polymeric biomaterials on the in vitro osteogenic induction of human stem cells. An electronic search in three databases (MEDLINE, SCOPUS, and Web of Science) was performed for articles that were published before May 2018. In vitro studies were included if they met the following criteria: (1) the use of polymeric scaffolds (natural or synthetic); (2) the co-culture of human stem cells with the scaffold; and (3) cell viability, proliferation, and osteogenic differentiation assays. The main characteristics of the published studies were summarized, and a quality assessment tool was used to analyze methodological features. Eighty-eight potential articles were firstly retrieved. Thirteen were eligible for qualitative analysis. Only three studies characterized cell stemness. Nanostructure of the scaffolds showed a significant influence on viability, proliferation, and osteogenic differentiation of human stem cells. Combination of porosity between 72 and 93% and a large range diameter between 50 and 224 μm resulted in more remarkable cellular proliferation and differentiation. Porous polymeric scaffolds can be functionalized by stem cells leading to osteogenic induction. High standards of laboratory practice and accurate methodological reporting are essential for the credibility of the results.     

Obesity and Bone Health: A Complex Relationship

Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.     

In vivo assessment of the corrosion of nickel–titanium orthodontic archwires by using scanning electron microscopy and atomic force microscopy

This study was undertaken to assess in vivo the corrosion in two commercial nickel–titanium (NiTi) orthodontic archwires removed from the oral cavity of patients using fluoride mouthwashes. Five volunteers took part in this study on the corrosion behavior of two brands of NiTi archwires (3M and AO (brand of archwire)) during use of two mouthwashes with neutral sodium fluoride 1.1%, one with acidulated fluoride 1.1%, and one with placebo and a control group. Each patient used one mouthwash in three different periods of time for 1 min a day for 30 days. The archwires were assessed with scanning electron microscopy and atomic force microscopy for qualitative and quantitative analysis. The values obtained with atomic force microscopy (AFM) were submitted to normality test, two‐way analysis of variance, and Tukey's test at a significance level of 5%. The AFM images showed a gradual qualitative increase in the roughness of both types of wire between the treatments: control < placebo < neutral fluoride < acidulated fluoride. The arithmetic average of the roughness and root mean square of the roughness were similar. As for 3M archwires, only the acidulated fluoride group differed statistically from the others. As for AO archwires, the control and placebo groups did not differ from each other, but differed from the other fluoride treatments. The group using neutral fluoride also differed significantly from the acidulated fluoride group. 3M archwires were not affected by daily oral challenges. AO archwires were not affected by daily oral challenges either; their association with fluoride, either neutral or acidulated, increased their roughness.     

A Sensitivity-Based Design Space Exploration Methodology for Embedded Systems

In this paper, we propose a system-level design methodology for the efficient exploration of the architectural parameters of the memory sub-systems, from the energy-delay joint perspective. The aim is to find the best configuration of the memory hierarchy without performing the exhaustive analysis of the parameters space. The target system architecture includes the processor, separated instruction and data caches, the main memory, and the system buses. To achieve a fast convergence toward the near-optimal configuration, the proposed methodology adopts an iterative local-search algorithm based on the sensitivity analysis of the cost function with respect to the tuning parameters of the memory sub-system architecture. The exploration strategy is based on the Energy-Delay Product (EDP) metric taking into consideration both performance and energy constraints. The effectiveness of the proposed methodology has been demonstrated through the design space exploration of a real-world case study: the optimization of the memory hierarchy of a MicroSPARC2-based system executing the set of Mediabench benchmarks for multimedia applications. Experimental results have shown an optimization speedup of 2 orders of magnitude with respect to the full search approach, while the near-optimal system-level configuration is characterized by a distance from the optimal full search configuration in the range of 2%.     

Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients.     

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.     

Leptin Signaling in Obesity and Colorectal Cancer

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.