Current advances concerning the most cited metal ions doped bioceramics and silicate-based bioactive glasses for bone tissue engineering

Studies related to biomaterials that stimulate the repair of living tissue have increased considerably, improving the quality of many people's lives that require surgery due to traumatic accidents, bone diseases, bone defects, and reconstructions. Among these biomaterials, bioceramics and bioactive glasses (BGs) have proved to be suitable for coating materials, cement, scaffolds, and nanoparticles, once they present good biocompatibility and degradability, able to generate osteoconduction on the surrounding tissue. However, the role of biomaterials in hard tissue engineering is not restricted to a structural replacement or for guiding tissue regeneration. Nowadays, it is expected that biomaterials develop a multifunctional role when implanted, orchestrating the process of tissue regeneration and providing to the body the capacity to heal itself. In this way, the incorporation of specific metal ions in bioceramics and BGs structure, including magnesium, silver, strontium, lithium, copper, iron, zinc, cobalt, and manganese are currently receiving enhanced interest as biomaterials for biomedical applications. When an ion is incorporated into the bioceramic structure, a new category of material is created, which has several unique properties that overcome the disadvantages of primitive material and favors its use in different biomedical applications. The doping can enhance handling properties, angiogenic and osteogenic performance, and antimicrobial activity. Therefore, this review aims to summarize the effect of selected metal ion dopants into bioceramics and silicate-based BGs in bone tissue engineering. Furthermore, new applications for doped bioceramics and BGs are highlighted, including cancer treatment and drug delivery.     

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

SR ARQ packet delay statistics on markov channels in the presence of variable arrival rate

In this letter we investigate the packet delay statistics of a fully reliable selective repeat ARQ scheme by considering a discrete time Markov channel with non-instantaneous feedback and assigned round-trip delay m. Our focus is on studying the impact of the arrival process on the delay experienced by a packet. An exact model is introduced to represent the system constituted by the transmitter buffer, the m round-trip slots, and the channel state. By means of this model, we evaluate and discuss the delay statistics and we analyze the impact of the system parameters, in particular the packet arrival rate, on the delay statistics     

Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

IL-4- and IL-5-secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections

Helminth infections in humans and animals are associated with strong T helper 2 (Th2) responses. To determine whether parasite-derived Ag preferentially expand a Th2-like cell population, a filter immunoplaque assay was used to enumerate the frequencies (F0) of PBMC and CD4(+)-enriched PBMC from individuals with helminth infections secreting selected cytokines in response to parasite-derived (PAg) and nonparasite antigens (NPAg). In 20 individuals with lymphatic filariasis, frequency analysis of PBMC secreting IL-4 and IFN-gamma indicated that the F0 of PAg-specific IL-4-secreting cells (geometric mean F0 (GM): 1/12,100) was 57-fold higher than the corresponding F0 of NPAg-reactive cells (GM: 1/692,000; p < 0.02). In marked contrast, the F0 of IFN-gamma-secreting cells responding to PAg (GM: 1/2,700) did not differ from those of cells specific for NAPg (GM: 1/3,400; p = 0.83). In another group of helminth-infected individuals, the F0 of highly enriched CD4+ cells secreting IL-4 and IL-5 in response to PAg (GMs: 1/2,600 and 1/5,600 CD4+ cells, respectively) were also found to be significantly higher than those specific for NPAg (GMs: 1/291,000 and 1/303,000 CD4+; p < 0.05 and p < 0.01, respectively), whereas the corresponding F0 of IFN-gamma- and granulocyte-macrophage-CSF-secreting cells were equivalent for PAg and NPag. Furthermore, the proportion of PAg-specific IL-4- and IL-5-secreting CD4+ cells relative to all cells secreting the given cytokine were approximately 29-fold higher than the proportion of NPAg-specific cells secreting these cytokines. Again, the corresponding proportions of Ag-specific IFN-gamma-and GM-CSF-secreting CD4+ cells were equivalent for PAg and NPAg. Thus, in this ex vivo system, a circulating population of IL-4- and IL-5-secreting (Th2-like) cells has been shown to exist in humans; PAg appears to expand these cells preferentially.