45S5 bioglass-derived glass-ceramic scaffolds containing niobium obtained by gelcasting method

Scaffolds of bioglass derived from BG45S5 (45 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O and 6 wt% P2O5) containing 10 wt% niobium were prepared by gelcasting method. The scaffolds presented a 3D porous structure with interconnected and spherical pores (pore size range 100 µm to 500 µm) and high porosity (89%), similar to trabecular architecture of spongy bone. The compressive strength was 0.18 ± 0.03 MPa which is acceptable for bone repair applications. The in vitro biological studies showed cytocompatibility for human osteoblastic cells as well tendency for higher alkaline phosphatase activity. Therefore, the findings here suggest the great potential of the scaffolds for using in bone tissue engineering.This work was supported by São Paulo Research Foundation - FAPESP (Grant: 2015-24659-7), National Council for Scientific and Technological Development (Grant: 456461/2014-0) and Erasmus Mundus Program (Be Mundus Project). The authors acknowledge the use of the analytical instrumentation facility at I3S-Instituto de Investigação e Inovação em Saúde (Portugal) and the provision of Nb2O5 by CBMM - Companhia Brasileira de Metalurgia e Mineração

Synthesis of new proteomimetic quinazolinone alkaloids and evaluation of their neuroprotective and antitumor effects

New quinazolinone derivatives of the marine-derived alkaloids fiscalin B (3) and fumiquinazoline G (1), with neuroprotective and antitumor effects, were synthesized. Eleven quinazolinone-containing indole alkaloids were synthesized, proceeding the anti analogs via a one-pot method, and the syn analogs by the Mazurkiewicz-Ganesan approach. The neuroprotection capacity of these compounds on the rotenone-damage human neuroblastoma cell SH-SY5y was evaluated using the MTT assay. Compounds 1, 3, 5, and 7 showed more than 25% protection. The antitumor activity was investigated using the sulforhodamine B assay and some compounds were tested on the non-malignant MCF-12A cells. Fumiquinazoline G (1) was the most potent compound, with GI50 values lower than 20 µM. Compounds 5, 7, and 11 were more active in all tumor cell lines when compared to their enantiomers. Compounds 5, 7, 10, and 11 had very little effect in the viability of the non-malignant cells. Differences between enantiomeric pairs were also noted as being essential for these activities the S-configuration at C-4. These results reinforce the previously described activities of the fiscalin B (3) as substance P inhibitor and fumiquinazoline G (1) as antitumor agent showing potential as lead compounds for the development of drugs for treatment of neurodegenerative disorders and cancer, respectively.This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT—Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the program PT2020. The authors thank to national funds provided by FCT—Foundation for Science and Technology and European Regional Development Fund (ERDF) and COMPETE under the Strategic Funding UID/Multi/04423/2013, the projects POCI-01-0145-FEDER-028736 and PTDC/MAR-BIO/4694/2014 (POCI-01-0145-FEDER-016790; 3599-PPCDT)

Influence of PLLA/PCL/HA scaffold fiber orientation on mechanical properties and osteoblast behavior

Scaffolds based on aligned and non-aligned poly (L-lactic acid) (PLLA)/polycaprolactone (PCL) fibers obtained by electrospinning, associated to electrosprayed hydroxyapatite (HA) for tissue engineering applications were developed and their performance was compared in terms of their morphology and biological and mechanical behaviors. The morphological results assessed by scanning electron microscopy showed a mesh of PLLA/PCL fibers (random and perfectly aligned) associated with aggregates of nanophased HA. Fourier transform infrared spectrometry confirmed the homogeneity in the blends and the presence of nanoHA in the scaffold. As a result of fiber alignment a 15-fold increase in Young's Modulus and an 8-fold increase in tensile strength were observed when compared to non-aligned fibers. In PLLA/PCL/HA scaffolds, the introduction of nanoHA caused a remarkable improvement of the mechanical strength of this material acting as a reinforcement, enhancing the response of these constructs to tensile stress. In vitro testing was evaluated using osteoblast (MC3T3-E1) cells. The results showed that both fibrous scaffolds were able to support osteoblast cell adhesion and proliferation and that fiber alignment induced increased cellular metabolic activity. In addition, the adhesion and proliferation of Staphylococcus aureus were evaluated and a lower number of colony forming units (CFUs) was obtained in the scaffolds with aligned fibers.Project UID/BIM/04293/2019 by FCT/MCTES through Portuguese Funds

Modelling outcomes after paediatric brain injury with admission laboratory values: a machine-learning approach.

BACKGROUND: Severe traumatic brain injury (TBI) is a leading cause of mortality in children, but the accurate prediction of outcomes at the point of admission remains very challenging. Admission laboratory results are a promising potential source of prognostic data, but have not been widely explored in paediatric cohorts. Herein, we use machine-learning methods to analyse 14 different serum parameters together and develop a prognostic model to predict 6-month outcomes in children with severe TBI. METHODS: A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between 2009 and 2013 with a TBI. The data for 14 admission serum parameters were recorded. Logistic regression and a support vector machine (SVM) were trained with these data against dichotimised outcomes from the recorded 6-month Glasgow Outcome Scale. RESULTS: Ninety-four patients were identified. Admission levels of lactate, H+, and glucose were identified as being the most informative of 6-month outcomes. Four different models were produced. The SVM using just the three most informative parameters was the best able to predict favourable outcomes at 6 months (sensitivity = 80%, specificity = 99%). CONCLUSIONS: Our results demonstrate the potential for highly accurate outcome prediction after severe paediatric TBI using admission laboratory data

The Percentage of [−2]Pro–Prostate-Specific Antigen and the Prostate Health Index Outperform Prostate-Specific Antigen and the Percentage of Free Prostate-Specific Antigen in the Detection of Clinically Significant Prostate Cancer and Can Be Used as Reflex Tests

Context.—: There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. Objective.—: To evaluate the clinical utility of [-2]pro-prostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). Design.—: Two hundred thirty-seven men (PSA: 2-10 ng/mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. Results.—: Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: ≥1.25%) and PHI (cutoff: ≥27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: ≥1.12% and ≥24 for %[-2]proPSA and PHI, respectively). Conclusions.—: The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies.info:eu-repo/semantics/publishedVersio

AB0747 MATERNAL AND FETAL OUTCOMES IN PREGNANT WOMEN WITH JUVENILE IDIOPATHIC ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW

info:eu-repo/semantics/publishedVersio

Radiological Correlates of Raised Intracranial Pressure in Children: A Review.

Radiological assessment of the head is a routine part of the management of traumatic brain injury. This assessment can help to determine the requirement for invasive intracranial pressure (ICP) monitoring. The radiological correlates of elevated ICP have been widely studied in adults but far fewer specific pediatric studies have been conducted. There is, however, growing evidence that there are important differences in the radiological presentations of elevated ICP between children and adults; a reflection of the anatomical and physiological differences, as well as a difference in the pathophysiology of brain injury in children. Here in, we review the radiological parameters that correspond with increased ICP in children that have been described in the literature. We then describe the future directions of this work and our recommendations in order to develop non-invasive and radiological markers of raised ICP in children

Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches

PMCID: PMC3668194SEP was directly funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. SN acknowledges support from the Oxford NIHR Biomedical Research Centre and from the Oxford British Heart Foundation Centre of Research Excellence. SP and PL are funded by a BHF Senior Clinical Research fellowship. RC is supported by a BHF Research Chair and acknowledges the support of the Oxford BHF Centre for Research Excellence and the MRC and Wellcome Trust. PMM gratefully acknowledges training fellowships supporting his laboratory from the Wellcome Trust, GlaxoSmithKline and the Medical Research Council

Thresholds for identifying pathological intracranial pressure in paediatric traumatic brain injury.

Intracranial pressure (ICP) monitoring forms an integral part of the management of severe traumatic brain injury (TBI) in children. The prediction of elevated ICP from imaging is important when deciding on whether to implement invasive ICP monitoring for a patient. However, the radiological markers of pathologically elevated ICP have not been specifically validated in paediatric studies. Here in, we describe an objective, non-invasive, quantitative method of stratifying which patients are likely to require invasive monitoring. A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between January 2009 and December 2016 with a TBI requiring invasive neurosurgical monitoring was performed. Radiological biomarkers of TBI (basal cistern volume, ventricular volume, volume of extra-axial haematomas) from CT scans were measured and correlated with epochs of continuous high frequency variables of pressure monitoring around the time of imaging. 38 patients were identified. Basal cistern volume was found to correlate significantly with opening ICP (r = -0.53, p < 0.001). The optimal threshold of basal cistern volume for predicting high ICP ([Formula: see text]20 mmHg) was a relative volume of 0.0055 (sensitivity 79%, specificity 80%). Ventricular volume and extra-axial haematoma volume did not correlate significantly with opening ICP. Our results show that the features of pathologically elevated ICP in children may differ considerably from those validated in adults. The development of quantitative parameters can help to predict which patients would most benefit from invasive neurosurgical monitoring and we present a novel radiological threshold for this.We gratefully acknowledge financial support as follows. Research support: the Medical Research Council (MRC, Grant Nos. G0600986 ID79068 and G1002277 ID98489) and the National Institute for Health Research Biomedical Research Centre (NIHR BRC) Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Authors’ support: Peter J Hutchinson – NIHR Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship, NIHR Global Health Research Group on Neurotrauma, and NIHR Cambridge BRC. Joseph Donnelly is supported by a Woolf Fisher Scholarship. MC- NIHR BRC