Congenital anomalies in low- and middle-income countries: the unborn child of global surgery.

Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability

Targeting human osteoarthritic chondrocytes with ligand directed bacteriophage-based particles

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive deterioration and loss of articular cartilage. There is currently no treatment to reverse the onset of OA. Thus, we developed a targeted delivery strategy to transfer genes into primary human chondrocytes as a proof-of-concept study. We displayed a chondrocyte-affinity peptide (CAP) on the pIII minor coat protein of the M13 filamentous bacteriophage (phage)-based particle carrying a mammalian transgene cassette under cytomegalovirus CMV promoter and inverted terminal repeats (ITRs) cis elements of adeno-associated virus serotype 2 (AAV-2). Primary human articular chondrocytes (HACs) were used as an in vitro model, and the selectivity and binding properties of the CAP ligand in relation to the pathogenic conditions of HACs were characterized. We found that the CAP ligand is highly selective toward pathogenic HACs. Furthermore, the stability, cytotoxicity, and gene delivery efficacy of the CAP-displaying phage (CAP.Phage) were evaluated. We found that the phage particle is stable under a wide range of temperatures and pH values, while showing no cytotoxicity to HACs. Importantly, the CAP.Phage particle, carrying a secreted luciferase (Lucia) reporter gene, efficiently and selectively delivered transgene expression to HACs. In summary, it was found that the CAP ligand preferably binds to pathogenic chondrocytes, and the CAP.Phage particle successfully targets and delivers transgene to HACs

Factors affecting compressive strength and expansion due to alkali-silica reaction of fly ash-based alkaline activated mortar

Data availability: Data will be made available on request.Copyright © 2023 The Author(s). The development of environmentally friendly alkaline-activated materials (AAMs) holds promise, as AAMs can be derived from waste materials. This study aims to investigate the factors influencing (i) compressive strength and (ii) expansion due to alkali-silica reaction (ASR) in AAMs. These factors include alkaline concentration, heat curing conditions, fineness of fly ash, and the liquid alkaline-to-binder (L/B) ratio. The findings indicate that the higher concentrations of NaOH solution led to an increase in AAM compressive strength due to the enhanced dissolution and polymerization rates in a more alkaline environment. Heat curing stimulated chemical reactions and structure formation, while the reduced water content resulted in lower porosity and higher compressive strength in the hardened cement. Finer fly ash yielded greater compressive strength than coarser ash, as its smaller spherical particles contributed to denser and firmer structures. The presence of calcium minerals, from both Ordinary Portland Cement (OPC) and high-calcium fly ash, bolstered the strength of hardened products. Moreover, calcium minerals like CaO, Ca(OH)2, and CaSO4 were found to induce ASR expansion by promoting gel formation, leading to later-stage expansion in the hardened cement or concrete. However, finely milled fly ash as a precursor significantly reduced ASR expansion in AAMs, by approximately 40% compared to ordinary Portland cement. This study provides valuable insights for civil engineers for better understanding of AAM behavior and makes contributions to the safety and sustainability of cement and concrete systems.Thailand Science Research and Innovation (TSRI) under Fundamental Fund 2023 (Project: Advanced Construction Towards Thailand 4.0); Department of Civil Engineering, Faculty of Engineering, Chiang Mai University (CMU)

A new approach to assessing the health benefit from obesity interventions in children and adolescents: the assessing cost-effectiveness in obesity project

OBJECTIVE: To report on a new modelling approach developed for the assessing cost-effectiveness in obesity (ACE-Obesity) project and the likely population health benefit and strength of evidence for 13 potential obesity prevention interventions in children and adolescents in Australia. METHODS: We used the best available evidence, including evidence from non-traditional epidemiological study designs, to determine the health benefits as body mass index (BMI) units saved and disability-adjusted life years (DALYs) saved. We developed new methods to model the impact of behaviours on BMI post-intervention where this was not measured and the impacts on DALYs over the child\u27s lifetime (on the assumption that changes in BMI were maintained into adulthood). A working group of stakeholders provided input into decisions on the selection of interventions, the assumptions for modelling and the strength of the evidence. RESULTS: The likely health benefit varied considerably, as did the strength of the evidence from which that health benefit was calculated. The greatest health benefit is likely to be achieved by the \u27Reduction of TV advertising of high fat and/or high sugar foods and drinks to children\u27, \u27Laparoscopic adjustable gastric banding\u27 and the \u27multi-faceted school-based programme with an active physical education component\u27 interventions. CONCLUSIONS: The use of consistent methods and common health outcome measures enables valid comparison of the potential impact of interventions, but comparisons must take into account the strength of the evidence used. Other considerations, including cost-effectiveness and acceptability to stakeholders, will be presented in future ACE-Obesity papers. Information gaps identified include the need for new and more effective initiatives for the prevention of overweight and obesity and for better evaluations of public health interventions

Doxorubicin improves cancer cell targeting by filamentous phage gene delivery vectors.

Merging targeted systemic gene delivery and systemic chemotherapy against cancer, chemovirotherapy, has the potential to improve chemotherapy and gene therapy treatments and overcome cancer resistance. We introduced a bacteriophage (phage) vector, named human adeno-associated virus (AAV)/phage or AAVP, for the systemic targeting of therapeutic genes to cancer. The vector was designed as a hybrid between a recombinant adeno-associated virus genome (rAAV) and a filamentous phage capsid. To achieve tumor targeting, we displayed on the phage capsid the double-cyclic CDCRGDCFC (RGD4C) ligand that binds the alpha-V/beta-3 (αvβ3) integrin receptor. Here, we investigated a combination of doxorubicin chemotherapeutic drug and targeted gene delivery by the RGD4C/AAVP vector. Firstly, we showed that doxorubicin boosts transgene expression from the RGD4C/AAVP in two-dimensional (2D) cell cultures and three-dimensional (3D) tumor spheres established from human and murine cancer cells, while preserving selective gene delivery by RGD4C/AAVP. Next, we confirmed that doxorubicin does not increase vector attachment to cancer cells nor vector cell entry. In contrast, doxorubicin may alter the intracellular trafficking of the vector by facilitating nuclear accumulation of the RGD4C/AAVP genome through destabilization of the nuclear membrane. Finally, a combination of doxorubicin and RGD4C/AAVP-targeted suicide gene therapy exerts a synergistic effect to destroy human and murine tumor cells in 2D and 3D tumor sphere settings

Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic Dictyostelium discoideum: assessing stress and developmental competency post treatment

Bio-electrospraying (BES) and aerodynamically assisted bio-jetting (AABJ) have recently been established as important novel biospray technologies for directly manipulating living cells. To elucidate their potential in medical and clinical sciences, these bio-aerosol techniques have been subjected to increasingly rigorous investigations. In parallel to these studies, we wish to introduce these unique biotechnologies for use in the basic biological sciences, for handling a wide range of cell types and systems, thus increasing the range and the scope of these techniques for modern research. Here, the authors present the analysis of the new use of these biospray techniques for the direct handling of the simple eukaryotic biomedical model organism Dictyostelium discoideum. These cells are widely used as a model for immune cell chemotaxis and as a simple model for development. We demonstrate that AABJ of these cells did not cause cell stress, as defined by the stress-gene induction, nor affect cell development. Furthermore, although BES induced the increased expression of one stress-related gene (gapA), this was not a generalized stress response nor did it affect cell development. These data suggest that these biospray techniques can be used to directly manipulate single cells of this biomedical model without inducing a generalized stress response or perturbing later development

Investigation of hard-burn and soft-burn lime kiln dust as alternative materials for alkali-activated binder cured at ambient temperature

Copyright © 2020 The Author(s). As climate change becomes a severe concern, the development of green technology becomes a goal for many sectors, including the construction material sector. Ordinary Portland cement (OPC), the main constituent of concrete production, is a primary contributor to releasing carbon dioxide (CO2) into the atmosphere. Some alternative cementitious materials have been studied to reduce the massive amount of OPC consumption. Lime kiln dust (LKD), a by-product of quicklime production, is produced in abundance worldwide and mostly disposed of in landfills. The two types of LKD, soft-burn and hard-burn, are high-potential wastes that can be developed as alternative cementitious binders using the alkali-activated binder (AAB) technology. This study investigates the mixture designation and properties of LKD-based AAB when cured at ambient temperature. The results show that an ambient-cured soft-burn LKD-AAB achieved practical workability with an 8 M NaOH solution, 1.50 of sodium silicate-to-sodium hydroxide ratio (SS/SH), and 0.60 of liquid alkaline-to-binder ratio (L/B). A rapid setting behavior and an excellent compressive strength of 10.89 MPa at 28 days were revealed at room temperature curing. The ambient-cured hard-burn LKD-AAB could not provide the appropriate properties. However, the mixture of 20% hard-burn LKD and 80% soft-burn LKD resulted in an LKD-AAB mixture that meets the minimum requirement for low-strength cement applications. The positive outcome of this study may be the solution for of LKD wastes utilization in Thailand that addresses the challenge of developing ambient-cured AAB for in-field applications.Partially supported by Chiang Mai University; the fifth author would like to acknowledge the financial support of the Thailand Research Fund (TRF) under the TRF Distinguished Research Professor Grant No. DPG6180002; financial support and the raw materials for these experiments from Chememan Public Company Limited, Thailand

Laboratory-grade vs. industrial-grade NaOH as alkaline activator: The properties of coal fly ash based-alkaline activated material for construction

Case study.Data Availability: Data will be made available on request.Copyright © 2023 The Author(s). Alkaline-activated materials (AAM) are potentially low-carbon alternative binders for the cement industry. Most research studies related to AAM have been performed with high-purity laboratory-grade NaOH alkaline activators (Lab-grade). Gaining confidence in AAM beyond the laboratory scale in real applications remains a major challenge. To make this prospect more realistic, the viability of low-purity industrial-grade (Ind.-grade) and local no-grade alkaline activators was investigated. The strength results of Ind.-grade AAM were 15–20% lower than those of Lab-grade AAM. The purity of the Ind.-grade activator should be at least 98% to achieve the performance of Lab-grade AAM. The production cost of Ind.-grade AAM was 75–85% lower than that of Lab-grade AAM at the same activator concentration. It should be noted that the use of no-grade NaOH is not recommended for engineering purposes due to its uncertain quality and low purity. The combined benefits of low cost and high availability of Ind.-grade activators are expected to enhance the commercial viability of AAM as a sustainable alternative construction material for field applications.This work (grant no. RGNS 63–078) was supported by the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation (OPS MHESI), Thailand Science Research and Innovation (TSRI). Furthermore, this research work was partially supported by Chiang Mai University. The authors would like to express gratitude to the Department of Civil Engineering, Faculty of Engineering, Chiang Mai University (CMU), for providing equipment and facilities, as well as Mr. Witthawat Moonnee (M.Eng) who was working hard on this project. Special thanks to the cooperation of Brunel University London, UK and Imperial College London, UK. The last author would also like to acknowledge the support from the Research and Graduate Studies, Khon Kaen University

Influence of ammonia-contaminated fly ash from selective catalytic reduction process on the properties of Portland-fly ash blended cement and geopolymer composites

Data availability: Data will be made available on request.Fly ash, a by-product of coal-fired power plants, finds valuable application in the cement and concrete industry due to its pozzolanic properties. Environmental concerns necessitate the use of Selective Catalytic Reduction (SCR) systems to reduce nitrogen oxide emissions; however, this process introduces residual ammonia onto the fly ash, known as SCR-fly ash, which may affect its properties. This study investigates the characteristics and suitability of SCR-fly ash as a supplementary cementitious material in Portland cement and geopolymer cement composites, compared to conventional high-calcium fly ash. The results show that Portland-fly ash blended cement mixtures containing 20% SCR-fly ash achieve comparable engineering properties to those with high-calcium fly ash, with a slight reduction in compressive strength of ~3.4% at 28 days. Geopolymers with SCR-fly ash exhibit a significantly lower (~52.8%) compressive strength than that of high-calcium fly ash 28 days. However, SCR-fly ash requires a resting period of at least 20 days to reduce ammonia content before use. The larger particle size and presence of residual ammonia can react to form detrimental gypsum or ammonium salts that lead to reduced strength. Therefore, SCR-fly ash may need to be chemically treated to be suitable as a geopolymer precursor. Overall, this work provides crucial insights into the potential utilization of SCR-fly ash in the cement and concrete industry, promoting resource recovery and environmental sustainability.This research work was supported by Fundamental Fund 2025, Chiang Mai University. The authors would like to express their gratitude to the Department of Civil Engineering, Faculty of Engineering, Chiang Mai University, for providing the necessary equipment and facilities. Special thanks are due to Mr. Teerapad Jongwijak (M.Eng) for his dedicated efforts on this project. Thanks to the Electricity Generating Authority of Thailand (EGAT 68-N402000-11-IO.SS03N3008692) for their kind support

Efficacy of arginine depletion by ADI-PEG20 in an intracranial model of GBM

Glioblastoma multiforme (GBM) remains a cancer with a poor prognosis and few effective therapeutic options. Successful medical management of GBM is limited by the restricted access of drugs to the central nervous system (CNS) caused by the blood brain barrier (BBB). We previously showed that a subset of GBM are arginine auxotrophic because of transcriptional silencing of ASS1 and/or ASL and are sensitive to pegylated arginine deiminase (ADI-PEG20). However, it is unknown whether depletion of arginine in peripheral blood in vivo has therapeutic activity against intracranial disease. In the present work, we describe the efficacy of ADI-PEG20 in an intracranial model of human GBM in which tumour growth and regression are assessed in real time by measurement of luciferase activity. Animals bearing intracranial human GBM tumours of varying ASS status were treated with ADI-PEG20 alone or in combination with temozolomide and monitored for tumour growth and regression. Monotherapy ADI-PEG20 significantly reduces the intracranial growth of ASS1 negative GBM and extends survival of mice carrying ASS1 negative GBM without obvious toxicity. The combination of ADI-PEG20 with temozolomide (TMZ) demonstrates enhanced effects in both ASS1 negative and ASS1 positive backgrounds.Our data provide proof of principle for a therapeutic strategy for GBM using peripheral blood arginine depletion that does not require BBB passage of drug and is well tolerated. The ability of ADI-PEG20 to cytoreduce GBM and enhance the effects of temozolomide argues strongly for its early clinical evaluation in the treatment of GBM