Micro-CT studies on 3-D bioactive glass-ceramic scaffolds for bone regeneration

The aim of this study was the preparation and characterization of bioactive glass-ceramic scaffolds for bone tissue engineering. For this purpose, a glass belonging to the system SiO2-P2O5-CaO-MgO-Na2O-K2O (CEL2) was used. The sponge-replication method was adopted to prepare the scaffolds; specifically, a polymeric skeleton was impregnated with a slurry containing CEL2 powder, polyvinyl alcohol (PVA) as a binding agent and distilled water. The impregnated sponge was then thermally treated to remove the polymeric phase and to sinter the inorganic one. The obtained scaffolds possessed an open and interconnected porosity, analogous to cancellous bone texture, and with a mechanical strength above 2 MPa. Moreover, the scaffolds underwent partial bioresorption due to ion-leaching phe- nomena. This feature was investigated by X-ray computed microcomputed tomography (micro-CT). Micro-CT is a three-dimensional (3- D) radiographic imaging technique, able to achieve a spatial resolution close to 1 lm3. The use of synchrotron radiation allows the selected photon energy to be tuned to optimize the contrast among the different phases in the investigated samples. The 3-D scaffolds were soaked in a simulated body fluid (SBF) to study the formation of hydroxyapatite microcrystals on the scaffold struts and on the internal pore walls. The 3-D scaffolds were also soaked in a buffer solution (Tris-HCl) for different times to assess the scaffold bioresorp- tion according to the ISO standard. A gradual resorption of the pores walls was observed during the soakings both in SBF and in Tris- HC

The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways

Motivation: Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions

Association Between Sex Hormone Levels and Clinical Outcomes in Patients With COVID-19 Admitted to Hospital: An Observational, Retrospective, Cohort Study

Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. The median age was 73.5 years [IQR 61, 82]; 55.8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L, p =0.0378 and 3.7 vs. 8.5 nmol/L, p =0.0011, respectively). Deceased males had lower testosterone (2.4 vs. 4.8 nmol/L, p =0.0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0.0006). Testosterone was negatively associated with ARDS (OR 0.849 [95% CI 0.734, 0.982]), severe COVID-19 (OR 0.691 [95% CI 0.546, 0.874]), and in-hospital mortality (OR 0.742 [95% CI 0.566, 0.972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1.051 [95% CI 1.018, 1.084]), confirmed in both sex models. In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes.The research was funded by Italian Ministry of Health “Fondi Ricerca Corrente, Project L1P5” for IRCCS Sacro Cuore Don Calabria Hospital. The funding source had no role in the collection, analysis, or interpretation of data, the study design, or the writing of the paper.Peer reviewe

A Systems Biology Approach to Characterize the Regulatory Networks Leading to Trabectedin Resistance in an In Vitro Model of Myxoid Liposarcoma

Trabectedin, a new antitumor compound originally derived from a marine tunicate, is clinically effective in soft tissue sarcoma. The drug has shown a high selectivity for myxoid liposarcoma, characterized by the translocation t(12;16)(q13; p11) leading to the expression of FUS-CHOP fusion gene. Trabectedin appears to act interfering with mechanisms of transcription regulation. In particular, the transactivating activity of FUS-CHOP was found to be impaired by trabectedin treatment. Even after prolonged response resistance occurs and thus it is important to elucidate the mechanisms of resistance to trabectedin. To this end we developed and characterized a myxoid liposarcoma cell line resistant to trabectedin (402-91/ET), obtained by exposing the parental 402-91 cell line to stepwise increases in drug concentration. The aim of this study was to compare mRNAs, miRNAs and proteins profiles of 402-91 and 402-91/ET cells through a systems biology approach. We identified 3,083 genes, 47 miRNAs and 336 proteins differentially expressed between 402-91 and 402-91/ET cell lines. Interestingly three miRNAs among those differentially expressed, miR-130a, miR-21 and miR-7, harbored CHOP binding sites in their promoter region. We used computational approaches to integrate the three regulatory layers and to generate a molecular map describing the altered circuits in sensitive and resistant cell lines. By combining transcriptomic and proteomic data, we reconstructed two different networks, i.e. apoptosis and cell cycle regulation, that could play a key role in modulating trabectedin resistance. This approach highlights the central role of genes such as CCDN1, RB1, E2F4, TNF, CDKN1C and ABL1 in both pre- and post-transcriptional regulatory network. The validation of these results in in vivo models might be clinically relevant to stratify myxoid liposarcoma patients with different sensitivity to trabectedin treatment

Text comprehension in Down Syndrome: The role of lower and higher level abilities

The contribution of lower level linguistic abilities (study 1) and a higher level capacity, namely the use of context, (study 2), on text comprehension was studied. Participants were 16 individuals with Down syndrome aged between aged between 8 years 11 months and 16 years 10 months, and 16 children with typical development, aged between 5 years 11 months and 7 years 3 months, matched for the level of text comprehension. In study 1 the two groups were compared for receptive vocabulary and sentence comprehension: both of them were shown to play a role in text comprehension in Down syndrome. Since participants with Down syndrome had very low scores in sentence comprehension, study 2 tested the hypothesis that when sentences were presented within a brief context, individuals with Down syndrome would perform better. This hypothesis was confirmed and it was shown that contextual facilitation was closely related to text comprehension skills

Sonographic evaluation of bone fractures: a reliable alternative in clinical practice?

Abstract Objective The objective was to compare the diagnostic accuracy of conventional radiography and ultrasonography (US) for the diagnosis of suspected bone fractures. Method Eighty-six patients were assessed using conventional radiography and US on the affected bone district. Results Radiographic and sonographic findings were concordant in 93% of cases. In one case, US suggested a fracture not seen on radiographic assessment. Ultrasonography showed a sensitivity of 0.94 and a specificity of 0.92. Conclusion In clinical practice, US could become the first diagnostic approach

Contrast-Enhanced Ultrasound for Characterizing Lymph Nodes With Focal Cortical Thickening in Patients With Cutaneous Melanoma

OBJECTIVE: The aim of this study was to ascertain the utility of contrast-enhanced ultrasound in assessing the significance of focal cortical thickening in the lymph nodes of patients followed up after surgery for cutaneous melanoma. MATERIALS AND METHODS: Ultrasound was used to examine 460 consecutive patients to identify nodes with focal hypoechoic cortical thickening. Patients whose nodes revealed these features underwent contrast-enhanced ultrasound and ultrasound-guided fine-needle aspiration cytology (FNAC) focusing on the area of cortical thickening. Enhancement in the arterial and parenchymal phases was evaluated: A generalized homogeneous or intense enhancement was considered benign and the presence of a perfusion defect was considered metastatic. RESULTS: After exclusion of 24 patients with frank signs of malignancy at gray-scale ultrasound, the study included 436 patients. Focal hypoechoic cortical thickening was seen in 44 of 436 nodes in as many patients. In 29 nodes, the area of focal thickening showed contrast enhancement similar to that of the remaining cortex on contrast-enhanced ultrasound. In 15 nodes, the area of cortical thickening was less well vascularized than the adjacent parenchyma in the arterial phase and there were areas with perfusion defects that were more evident in the parenchymal phase. FNAC focusing on the areas of focal cortical thickening identified 13 metastatic nodes and 31 nodes with benign features. Contrast-enhanced ultrasound compared with FNAC correctly classified 42 of 44 nodes, showing a sensitivity of 100% and a specificity of 99.5%. CONCLUSION: Although our findings need to be confirmed in larger series, they indicate that contrast-enhanced ultrasound can be useful in clinical practice for characterizing focal cortical thickening in lymph nodes. The exclusion or identification of regional lymph node metastases is of fundamental importance in oncologic staging because this issue directly influences both the prognosis and the choice of therapeutic strategy

Potential use of contrast-enanched ultrasound (CEUS) in the detection of metastatic superficial lymph nodes in melanoma patients.

Abstract Purpose: Malignant melanoma represents a significant and growing public health burden worldwide. Ultrasonography is the most useful diagnostic modality for regional lymph nodal staging. Because any focal areas of cortical lobulation or thickening-swelling should also be considered as a sign of metastases, we are going to report the usefulness of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign or malignant lymph nodes in patients with malignant melanoma based on blood stream patterns and investigate the diagnostic capability. Patients and Methods: After the excision of cutaneous melanoma with positive excision margins but with negative sentinel lymph node, 540 patients underwent US of superficial lymph nodes. The inclusion criteria for CEUS consisted of both major signs (absence of the echogenic hilus, round shape, and peripheral capsular vascularity) and minor ones (the presence of focal cortical thickening). The diagnostic capability was evaluated by comparing the cytological findings with the enhancement pattern on CEUS.\u200a Results: US in combination with CEUS correctly classified 534/540 patients. CEUS applied to lymph nodes with focal cortical thickening on grayscale US confirmed great sensitivity (0.98) and specificity (0.99) but above all, it showed a markedly improved accuracy of 0.99. The likelihood ratios confirmed the good performance of the methods used. Conclusion: CEUS increases the diagnostic accuracy of US in the differential diagnosis of benign and malignant LNs but it also allows us, when possible, to avoid unnecessary invasive operations such as LN FNAC. Moreover, CEUS may guide FNAC in the case of focal cortical thickening on the basis of hypoperfusion, with a reduction in the number of false negatives and much earlier detection of nodal metastatic foci