Bioactive SiO2-K2O-CaO-P2O5 glass-ceramic scaffold prepared using polyurethane foam template

Abstract A glass-ceramic in the SiO2-K2O-CaO-P2O5 quaternary system was prepared by substituting the Na2O component with K2O to avoid Na2Ca2Si3O9 formation upon thermal treatment since this phase decreases apatite formation kinetics on glass material. To form the glass-ceramic, a modified sol-gel method involving solution precipitation, followed by reagents encapsulation in citric acid was adopted to enable the use of sodium metasilicate as a cheap substitute for traditional alkoxysilane silica precursors. The foam replication method using polyurethane foam as a sacrificial template was used to obtain the scaffold, which on analysis gave a porosity of 92% and an average pore size of 36±6 mm. In vitro bioactivity evaluation in simulated body fluid for a maximum of 14 days indicated the formation of hydroxyapatite on the sample surface. Phase analysis showed that CaSiO3 and K2CaSiO4 crystals formed in the sintered sample as the main phases, which exhibited biodegradability in simulated body fluid (SBF). Therefore, economically-derived porous bioactive glass-ceramic scaffolds based on the current method (a simple process) are feasible

Tumor-homing cytotoxic human induced neural stem cells for cancer therapy

Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSCTE), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSCTE in patient-derived GBM models of surgical and nonsurgical disease. Molecular and functional analysis revealed that our single-factor SOX2 TD strategy converted human skin fibroblasts into h-iNSCTE that were nestin+ and expressed pathways associated with tumor-homing migration in 4 days. Time-lapse motion analysis showed that h-iNSCTE rapidly migrated to human GBM cells and penetrated human GBM spheroids, a process inhibited by blockade of CXCR4. Serial imaging showed that h-iNSCTE delivery of the proapoptotic agent tumor necrosis factor-A-related apoptosis-inducing ligand (TRAIL) reduced the size of solid human GBM xenografts 250-fold in 3 weeks and prolonged median survival from 22 to 49 days. Additionally, h-iNSCTE thymidine kinase/ganciclovir enzyme/prodrug therapy (h-iNSCTE-TK) reduced the size of patient-derived GBM xenografts 20-fold and extended survival from 32 to 62 days. Mimicking clinical NSC therapy, h-iNSCTE-TK therapy delivered into the postoperative surgical resection cavity delayed the regrowth of residual GBMs threefold and prolonged survival from 46 to 60 days. These results suggest that TD of human skin into h-iNSCTE is a platform for creating tumor-homing cytotoxic cell therapies for cancer, where the potential to avoid carrier rejection could maximize treatment durability in human trials

COMPARATIVE ASSESSMENT OF STORAGE STABILITY OF GINGER-GARLIC AND CHEMICAL PRESERVATION ON FRUIT JUICE BLENDS

The study aimed at reduction of wastage of fruit, encourage production, consumption and preservation of fruit juice blends using garlic ginger filtrate with health benefits as biopreservative thus providing alternatives with biological advantage over chemical preservatives (ascorbic and benzoate acids) without altering the organoleptic and physicochemical properties of fruit juice blends. The study evaluated the potential of natural preservatives (ginger, garlic and ginger-garlic filtrates) in comparison with two conventional chemical preservatives (ascorbic and benzoate acids) for fruit juice blends preservation. The juice blend used was cashew, pineapple and watermelon. In terms of flavor and mouth feel, the order of preference of the juice were the preserved with 1% garlic-ginger > 1% ginger > 1% garlic > 1% ascorbic acid > and preserved with 1% sodium benzoate at ambient temperature. Maximum decrease in pH was observed in the juice sample that had no added preservative. Generally, all the fruit blends (preserved and unpreserved), with the exception of the one preserve with 1% ginger-garlic showed growth of bacteria after one week of storage. Juice blends preserved with the 1% ginger-garlic were most acceptable compared to other preservatives. The synergistic biopreservative ability observed with the ginger-garlic may be a preferable alternative to conventional preservatives

Fiscal federalism and economic development in Nigeria: An auto-regressive distributed lag approach

This study examines the impact of fiscal federalism on economic development in Nigeria for the period 1981–2017 using the auto-regressive distributed lag approach. The data for the study were sourced from various issues of Central Bank of Nigeria Statistical Bulletin and International Country Risk Guide. It was found that revenue decentralization with a coefficient of −2.15 significantly retarded economic development at 5%, while expenditure decentralization with a coefficient of 2.935 significantly increased economic development at 5%. The overall decentralization indicator, captured as simultaneity measure with a coefficient of 4.264 significantly increased economic development at 1%. From the empirical evidence, fiscal federalism will encourage economic development in Nigeria. These findings support and reinforce the need for greater decentralization of fiscal responsibilities to sub-national government. Also, government should enact legislations to improve bureaucratic quality, and implement appropriate security reforms to further strengthen law and order to ensure economic development in Nigeria

Design for occupational safety and health of workers in construction in developing countries: A study of architects in Nigeria

Purpose. Design for safety (DfS) of workers is amongst the prominent ways of tackling poor occupational safety and health performance in construction. However, in developing countries there is extremely limited research on DfS. This study thus makes an important contribution to the subject of DfS in developing countries by specifically examining the awareness and practice of DfS amongst architects within the construction sector of Nigeria. Materials and methods. A survey of architects, yielding 161 valid responses, was conducted. Results. While there is high awareness of the concept of DfS, the actual practice is low. Additionally, although there is high interest in DfS training, the engagement in DfS training is low. Significantly, awareness of DfS, training and education related to DfS, and membership of a design professional body have very limited bearing on the practice of DfS by architects. Conclusions. The findings are thus symptomatic of the prevalence of influential DfS implementation barriers within the construction sector. Industry stakeholders should seek to raise the profile of DfS practice within the sector. Furthermore, similar empirical studies in the construction sector of other developing countries would be useful in shedding light on the status of DfS in these countries

Development of a heptaplex PCR assay for identification of Staphylococcus aureus and CoNS with simultaneous detection of virulence and antibiotic resistance genes

Background Staphylococcal toxicity and antibiotic resistance (STAAR) have been menacing public health. Although vancomycin-resistant Staphylococcus aureus (VRSA) is currently not as widespread as methicillin-resistant S. aureus (MRSA), genome evolution of MRSA into VRSA, including strains engineered within the same patient under anti-staphylococcal therapy, may build up to future public health concern. To further complicate diagnosis, infection control and anti-microbial chemotherapy, non-sterile sites such as the nares and the skin could contain both S. aureus and coagulase-negative staphylococci (CoNS), either of which could harbour mecA the gene driving staphylococcal methicillin-resistance and required for MRSA-VRSA evolution. Results A new heptaplex PCR assay has been developed which simultaneously detects seven markers for: i) eubacteria (16S rRNA), ii) Staphylococcus genus (tuf), iii) Staphylococcus aureus (spa), iv) CoNS (cns), v) Panton-Valentine leukocidin (pvl), vi) methicillin resistance (mecA), and vii) vancomycin resistance (vanA). Following successful validation using 255 reference bacterial strains, applicability to analyse clinical samples was evaluated by direct amplification in spiked blood cultures (n = 89) which returned 100 % specificity, negative and positive predictive values. The new assay has LoD of 1.0x103 CFU/mL for the 16S rRNA marker and 1.0x104 CFU/mL for six other markers and completes cycling in less than one hour. Conclusion The speed, sensitivity (100 %), NPV (100 %) and PPV (100 %) suggest the new heptaplex PCR assay could be easily integrated into a routine diagnostic microbiology workflow. Detection of the cns marker allows for unique identification of CoNS in mono-microbial and in poly-microbial samples containing mixtures of CoNS and S. aureus without recourse to the conventional elimination approach which is ambiguous. In addition to the SA-CoNS differential diagnostic essence of the new assay, inclusion of vanA primers will allow microbiology laboratories to stay ahead of the emerging MRSA-VRSA evolution. To the best of our knowledge, the new heptaplex PCR assay is the most multiplexed among similar PCR-based assays for simultaneous detection of STAAR

Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells

Background: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells. Methods: Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways. Results: The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. Conclusions: Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the "go-or-grow" phenotypic switch of GBM cells.Fundação para a Ciência e Tecnologia (IF/00601/2012 to B.M.C.; IF/00111 to A.J.S; SFRH/BD/52287/2013 to A.I.O.; SFRH/BD/81495/2011 to S.I.A.; SFRH/BD/88121/2012 to J.V.C.; projects PTDC/SAU-GMG/113795/2009 to B.M.C.; PTDC/NEU-NMC/0205/2012, PTDC/NEU-SCC/7051/2014, PEst-C/SAU/LA0001/2013–2014 and UID/NEU/04539/2013 to B.M.), Liga Portuguesa Contra o Cancro (B.M.C.), Fundação Calouste Gulbenkian (B.M.C.) and Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC; to A.I.O.). Project co-financed by Programa Operacional Regional do Norte (ON.2—O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER), Programa Operacional Factores de Competitividade (COMPETE), and by The National Mass Spectrometry Network (RNEM) under the contract REDE/1506/REM/2005info:eu-repo/semantics/publishedVersio

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

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The evolving SARS-CoV-2 epidemic in Africa: insights from rapidly expanding genomic surveillance

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century