•Viability of self-healing in alkali-activated slag-based composites demonstrated.•Bacteria immobilized in expanded glass granules made from recycled glass.•Bio-based AAM specimens attained ...remarkably enhanced crack healing ratio.•Sorptivity coefficient decreased significantly by incorporating bacteria.•Using calcium lactate advantageous for economic and sustainability considerations.
Decarbonizing concrete manufacturing calls for sustainable construction materials since cement production contributes about 8% of global anthropogenic CO2 emissions. Alkali-activated materials (AAMs), usually derived from the activation of industrial by-products, have demonstrated great potential as alternatives to ordinary portland cement (OPC) concrete. However, AAMs are susceptible to cracking due to their inherent brittleness, which may compromise their service life and severely hinder wider acceptance and applications of AAMs. While bacteria-based crack self-healinghas attracted enormous research interests in OPC-based materials, only limited research has explored such self-healing in AAMs. Accordingly, this study aims at investigating the self-healing efficiency of alkali-activated slag-based composites using bacteria immobilized in expanded glass granules made from recycled glass. The effect of different calcium sources on the reaction kinetics, mechanical properties, capillary water absorption, and final self-healing compounds was investigated. The results reveal that the bio-based specimens attained a remarkably enhanced crack healing ratio, while no obvious self-healing was observed in abiotic control samples. Furthermore, the sorptivity coefficient decreased significantly by incorporating bacteria. Scanning electron microscopy with energy dispersive X-ray (SEM-EDX) analysis and Raman spectroscopy confirmed that calcite was the dominant self-healing product. This study suggests that using calcium lactate as the calcium source is advantageous owing to its economic and sustainability considerations.
The biocompatibility of two forms of calcined mesoporous silica particles, labeled as MCM41-cal and SBA15-cal, with fetal blood mononuclear cells was assessed in vitro.
Fetal mononuclear cells were ...isolated from umbilical cord blood and exposed to 0.5 mg/mL of MCM41-cal or SBA15-cal for several hours. Transmission electron micrographs confirmed the presence of particles in the cytosol of macrophages, neutrophils, and lymphocytes without noticeable damage to the cellular organelles. The particles (especially MCM41-cal) were in close proximity to plasma, and nuclear and mitochondrial membranes. Biocompatibility was assessed by a functional assay that measured cellular respiration, ie, mitochondrial O(2) consumption. The rate of respiration (k(c), in μM O(2) per minute per 10(7) cells) for untreated cells was 0.42 ± 0.16 (n = 10), for cells treated with MCM41-cal was 0.39 ± 0.22 (n = 5, P > 0.966) and for cells treated with SBA15-cal was 0.44 ± 0.13 (n = 5, P > 0.981).
The results show reasonable biocompatibility of MCM41-cal and SBA15-cal in fetal blood mononuclear cells. Future studies are needed to determine the potential of collecting fetal cells from a fetus or neonate, loading the cells in vitro with therapeutic MCM41-cal or SBA15-cal, and reinfusing them into the fetus or neonate.
Risankizumab has demonstrated efficacy in phase III trials in patients with moderate‐to‐severe plaque psoriasis. The exposure–response relationships for risankizumab efficacy (Psoriasis Area and ...Severity Index (PASI)75, PASI90, PASI100, and static Physician's Global Assessment (sPGA)0/1) at week 16 (N = 1,732) and week 52 (N = 598) as well as safety (incidence of any adverse event, serious adverse event, infection and infestation, or serious infection) over up to 52 weeks were characterized using the data from risankizumab phase II and III clinical trials in patients with moderate‐to‐severe plaque psoriasis. Impact of clinically relevant covariates was evaluated. Risankizumab phase III regimen (150 mg subcutaneously at weeks 0, 4, and every 12 weeks thereafter) achieved the plateau of the exposure–efficacy relationships with model‐estimated PASI90 and sPGA0/1 response probabilities of 77%, and 87%, respectively, at week 16 and 85%, and 88%, respectively, at week 52. There was no apparent relationship between risankizumab plasma exposure and the evaluated safety variables.
To evaluate the prevalence of tuberculosis (TB) stigma and to determine the relation between socio-demographic characteristics and TB stigma among TB cases and their controls in Gezira State, Sudan.
...A case-control study design was used. New smear-positive TB patients registered in Gezira State in 2010 (n = 425) and controls who attended the same health facility for other reasons (n < 850) formed the study population. Stigma was measured using a standard modified World Health Organization TB KAP (knowledge, attitudes, practice) instrument.
TB stigma did not differ between TB cases and controls; mild stigma was found in both groups. The higher degree of stigma among both groups was significantly associated with higher age, lower level of education, residence in rural areas, unemployment and poor TB awareness, while sex had no association with the degree of stigma in either group.
Although TB stigma among the Gezira population was found to be mild, it can affect treatment adherence. Empowering both TB patients and communities by increasing their knowledge through proper education programmes could effectively contribute to the effort of controlling TB in the state.
Elagolix is a novel oral gonadotropin releasing hormone receptor antagonist, that can suppress estradiol in a dose‐dependent manner. It is indicated for management of moderate‐to‐severe pain ...associated with endometriosis. A population exposure‐response model describing the relationship between elagolix exposure and changes in bone mineral density (BMD) was developed using data from four phase III studies in premenopausal women with endometriosis‐associated pain. Elagolix pharmacokinetic exposure‐dependent changes in BMD were described by an indirect‐response maximum effect (Emax) model through stimulation of bone resorption. African American race, higher body mass index (BMI), and lower type‐I collagen C‐telopeptide concentrations were significantly associated with higher baseline BMD. Higher BMI was significantly associated with higher bone formation rates. Simulations using the final model demonstrated that elagolix 150 mg q.d. dosing for 24 months is predicted to result in −1.45% (−2.04 to −0.814) decrease from baseline in BMD and were used to support corresponding dosing recommendations in the label.
Elagolix is a novel, oral gonadotropin‐releasing hormone receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding ...associated with uterine fibroids. Consistent with its mechanism of action, elagolix exhibited dose‐dependent suppression of estradiol (E2) in clinical studies. A dose‐response model that describes the relationship between elagolix dosages and average E2 levels was combined with a previously published quantitative systems pharmacology (QSP) model of calcium homeostasis to predict bone mineral density (BMD) changes during and following elagolix treatment. In the QSP model, changes in E2 levels were linked to downstream changes in markers of bone resorption (carboxyterminal cross‐linked telopeptide of type 1 collagen CTX), formation (N‐terminal propeptide of type 1 procollagen P1NP) and BMD. The BMD, CTX, and P1NP predictions by the QSP model were validated against observed data from four phase III clinical trials of elagolix in premenopausal women with endometriosis. BMD, CTX, and P1NP were successfully described by the QSP model, without any model fitting, suggesting that the model was validated for further predictions of elagolix effects on BMD. Simulations using the validated QSP model demonstrated that elagolix 150 mg once daily dosing for 24 months is predicted to result in −0.91% change from baseline in lumbar spine BMD. The QSP model simulation results were part of the totality of evidence to support the approved duration of therapy for elagolix 150 mg once daily in patients with endometriosis.
The role of microRNAs (miRNAs) in the pathogenesis of cardiovascular disease has been extensively studied. miRNAs have been highlighted as an important physiological regulator for activities like ...cardiac protection. miRNAs are present in the circulation, and they have been investigated as physiological markers, especially in the condition of heart failure. However, there is less compelling verification that miRNAs can outperform traditional biomarkers. However, clinical evidence is still required. In this review article, we explored the feasibility of miRNAs as diagnostic biomarkers for heart failure in a systematic study. Searching in the PubMed database to identify miRNA molecules that are differentially expressed between groups of patients with heart failure or heart disease and controls, throughout the investigation, we discovered no significant overlap in differentially expressed miRNAs. Only four miRNAs (“miR-126,” “miR-150-5p,” “hsa-miR-233,” and “miR-423-5p”) were differentially expressed. Results from our review show that there is not enough evidence to support the use of miRNAs as biomarkers in clinical settings.
Cardioplegic cardioprotection strategies used during paediatric open-heart surgery remain suboptimal. Sildenafil, a phosphodiesterase 5 (PDE-5) inhibitor, has been shown to be cardioprotective ...against ischemia/reperfusion injury in a variety of experimental models and this study therefore tested the efficacy of supplementation of cardioplegia with sildenafil in a piglet model of cardiopulmonary bypass and arrest, using both cold and warm cardioplegia protocols. Piglets were anaesthetized and placed on coronary pulmonary bypass (CPB), the aorta cross-clamped and the hearts arrested for 60 min with cardioplegia with or without sildenafil (10 nM). Twenty minutes after removal of cross clamp (reperfusion), attempts were made to wean the pigs from CPB. Termination was carried out after 60 min reperfusion. Throughout the protocol blood and left ventricular tissue samples were taken for analysis of selected metabolites (using HPLC) and troponin I. In both the cold and warm cardioplegia protocols there was evidence that sildenafil supplementation resulted in faster recovery of ATP levels, improved energy charge (a measure of metabolic flux) and altered release of hypoxanthine and inosine, two purine catabolites. There was no effect on troponin release within the studied short timeframe. In conclusion, sildenafil supplementation of cardioplegia resulted in improved cardiac energetics in a translational animal model of paediatric CPB surgery.
Background: Tuberculosis (TB) is among the top ten causes of global mortality. Sudan is among the countries with high TB control programme was established. Since its establishment, however, the ...programme has never been adequately assessed. Aim: To evaluate and describe the tuberculosis control programme in Khartoum State, Sudan in 2006; to find out if the programme achieved its global targeted goals; and to identify the challenges and needs for performing a good standard tuberculosis control programme. Methods: A descriptive cross-sectional and retrospective study design was used. The study population was tuberculosis control departments at the levels of the state (n = 1), localities (n = 7), health areas (n = 19) and health facilities in (n = 42). Records review and group interviews were used to collect the required data. Results: The study found that the control programme in Khartoum State achieved a 77.2% case detection rate of the smear-postive cases, and 73.5% treatment success rate, and a case fatality rate of 2.2%, treatment failure rate of 2.2%, and default rate of 14.1%. There was no system to detect the prevalence of MDR-TB (multi-drug resistant or HIV (human immunodeficiency virus) among the TB cases. The programme was not well implemented at locality or health area levels. Conversely, drugs and laboratory supply systems were functioning well. Conclusions: The tuberculosis control programme in Khartoum State is centralized, not updated, and does not achieve the targeted goals.
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