Constant Release Research Articles

Influence of the Acceptor Fluid on the Bupivacaine Release from the Prospective Intra-Articular Methylcellulose Hydrogel.

Injections are one way of delivering drugs directly to the joint capsule. Employing this possibility, local anesthetic, such as bupivacaine (Bu), in the form of the suspension can be administered. The aim of this work was to propose a methylcellulose-based hydrogel-incorporated bupivacaine for intra-articular injections and to study the release kinetics of the drug from the hydrogel to different acceptor media, reflecting the synovial fluid of a healthy joint and the synovial fluid of an inflamed joint. The drug release studies were performed employing the flow apparatus. The drug was released to four different acceptor fluids: phosphate buffer pH = 7.4 (PBS7.4), phosphate buffer pH = 6.8 (PBS6.8), phosphate buffer pH = 7.4 with the high-molecular-weight sodium hyaluronate (PBS7.4H), and phosphate buffer pH = 6.8 with the low-molecular-weight sodium hyaluronate (PBS6.8L). The investigation was carried out at the temperature of 37 °C. The absorbance of the Bu released was measured at the wavelength of 262 nm every 2 min for 24 h. The release profiles of Bu to the acceptor media PBS7.4, PBS6.8, PBS7.4H, and PBS6.8L were described best by the first-order kinetics and the second-order equation. According to these models, the release rate constants were the highest when Bu was released to the fluid PBS7.4 and were k1 = (7.20 ± 0.01) × 10-5 min-1 and k2 = (3.00 ± 0.04) × 10-6 mg-1 × min-1, respectively. The relative viscosity of the acceptor medium, its pH, and the addition of high-molecular-weight or low-molecular-weight sodium hyaluronate (HAH or HAL) to the acceptor fluid influenced the drug dissolution. The release of Bu into the medium reflecting healthy synovial fluid takes a different pattern from its release into the fluid of an inflamed joint.

Preparation, Characterization, and Antioxidant Properties of Self-Assembled Nanomicelles of Curcumin-Loaded Amphiphilic Modified Chitosan.

Curcumin (Cur) is a phytochemical with various beneficial properties, including antioxidant, anti-inflammatory, and anticancer activities. However, its hydrophobicity, poor bioavailability, and stability limit its application in many biological approaches. In this study, a novel amphiphilic chitosan wall material was synthesized. The process was carried out via grafting chitosan with succinic anhydride (SA) as a hydrophilic group and deoxycholic acid (DA) as a hydrophobic group; 1H-NMR, FTIR, and XRD were employed to characterize the amphiphilic chitosan (CS-SA-DA). Using a low-cost, inorganic solvent-based procedure, CS-SA-DA was self-assembled to load Cur nanomicelles. This amphiphilic polymer formed self-assembled micelles with a core-shell structure and a critical micelle concentration (CMC) of 0.093 mg·mL-1. Cur-loaded nanomicelles were prepared by self-assembly and characterized by the Nano Particle Size Potential Analyzer and transmission electron microscopy (TEM). The mean particle size of the spherical Cur-loaded micelles was 770 nm. The drug entrapment efficiency and loading capacities were up to 80.80 ± 0.99% and 19.02 ± 0.46%, respectively. The in vitro release profiles of curcumin from micelles showed a constant release of the active drug molecule. Cytotoxicity studies and toxicity tests for zebrafish exhibited the comparable efficacy and safety of this delivery system. Moreover, the results showed that the entrapment of curcumin in micelles improves its stability, antioxidant, and anti-inflammatory activity.

Dynamic Covalent Hydrogel as a Single-Dose Vaccine Adjuvant for Sustained Antigen Release and Significantly Elevated Humoral Immunity.

Vaccine is the most important way for fighting against infection diseases. However, multiple injections and unsatisfied immune responses are the main obstacles for current vaccine application. Herein, a dynamic covalent hydrogel (DCH) is used as a single-dose vaccine adjuvant for eliciting robust and sustained humoral immunity. By adjusting the mass ratio of the DCH gel, 10-30 d constant release of the loaded recombinant protein antigens is successfully realized, and it is proved that sustained release of antigens can significantly improve the vaccine efficacy. When loading SARS-CoV-2 RBD (Wuhan and Omicron BA.1 strains) antigens into this DCH gel, an over 32000 times and 8000 times improvement is observed in antigen-specific antibody titers compared to conventional Aluminum adjuvanted vaccines. The universality of this DCH gel adjuvant is confirmed in a Nipah G antigen test as well as a H1N1 influenza virus antigen test, with much improved protection of C57BL/6 mice against H1N1 virus infection than conventional Aluminum adjuvanted vaccines. This sustainably released, single-dose DCH gel adjuvant provides a new promising option for designing next-generation infection vaccines.

Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system.

Silk fibroin nanoparticles (FNP) have been increasingly investigated in biomedical fields due to their biocompatibility and biodegradability properties. To widen the FNP versatility and applications, and to control the drug release from the FNP, this study developed the Eudragit S100-functionalized FNP (ES100-FNP) as a pH-responsive drug delivery system, by two distinct methods of co-condensation and adsorption, employing the zwitterionic furosemide as a model drug. The particles were characterized by sizes and zeta potentials (DLS method), morphology (electron microscopy), drug entrapment efficiency and release profiles (UV-Vis spectroscopy), and chemical structures (FT-IR, XRD, and DSC). The ES100-FNP possessed nano-sizes of ∼200-350 nm, zeta potentials of ∼ -20 mV, silk-II structures, enhanced thermo-stability, non-cytotoxic to the erythrocytes, and drug entrapment efficiencies of 30%-60%, dependent on the formulation processes. Interestingly, the co-condensation method yielded the smooth spherical particles, whereas the adsorption method resulted in durian-shaped ones due to furosemide re-crystallization. The ES100-FNP adsorbed furosemide via physical adsorption, followed Langmuir model and pseudo-second-order kinetics. In the simulated oral condition, the particles could protect the drug in the stomach (pH 1.2), and gradually released the drug in the intestine (pH 6.8). Remarkably, in different pH conditions of 6.8, 9.5, and 12, the ES100-FNP could control the furosemide release rates depending on the formulation methods. The ES100-FNP made by the co-condensation method was mainly controlled by the swelling and corrosion process of ES100, and followed the Korsmeyer-Peppas non-Fickian transport mechanism. Whereas, the ES100-FNP made by the adsorption method showed constant release rates, followed the zero-order kinetics, due to the gradual furosemide dissolution in the media. Conclusively, the ES100-FNP demonstrated high versatility as a pH-responsive drug delivery system for biomedical applications.

Biopolymer-Based Hydrogel Incorporated with Naproxen Sodium and Lidocaine Hydrochloride for Controlled Drug Delivery.

Sodium hyaluronate (HA) is a natural polysaccharide. This biopolymer occurs in many tissues of living organisms. The regenerating, nourishing, and moisturizing properties as well as the rheological properties of HA enable its application in the pharmaceutical industry as a carrier of medicinal substances. The aim of this work was to assess the release of naproxen sodium (Nap) in the presence of lidocaine hydrochloride (Lid) from the biopolymer-based hydrogels and to determine the respective kinetic parameters of this process. The possible interaction between the HA polysaccharide carrier and the selected drugs was also investigated. Three hydrogels containing Nap and Lid with different concentrations of the biopolymer were prepared. The release of Nap was studied by employing USP apparatus 5. The infrared study and differential scanning calorimetry analysis of physical mixtures and dried formulations were performed. The highest amount of Nap was released from the formulation with the lowest concentration of the biopolymer. The most representative kinetic model that described the dissolution of Nap was obtained through the Korsmeyer-Peppas equation. The release rate constants were in the range of 1.0 ± 0.1 × 10-2 min-n-1.7 ± 0.1 × 10-2 min-n. Lid did not influence the dissolution of Nap from the formulations tested; however, in the desiccated samples of assessed formulations, the interaction between the polysaccharide and both drugs was observed.

Synthesis and drug release kinetics of ciprofloxacin from polyacrylamide/dextran/carbon quantum dots (PAM/Dex/CQD) hydrogels

Sustainable release of drug by utilizing β-cyclodextrin (β-CD) based inclusion complex (IC) is the prime objective of the present work. Herein, polyacrylamide/dextran containing carbon quantum dots (PAM/Dex/CQD) nanocomposite hydrogels are prepared by in situ polymerization of acrylamide. The incorporation of CQD triggers the change in orientation of the PAM/Dex polymeric chains to result the formation of stacked surface morphology of the hydrogel. The average particle size of CQD is found to be 4.13 nm from HRTEM analysis. As-synthesized nanocomposite hydrogel exhibits an optimum swelling ratio of 863 % in aqueous medium. The cytotoxicity study is conducted on HeLa cells by taking up to 2 μM concentration of the prepared nanocomposite hydrogel demonstrate 78 % cell viability. In present study, ciprofloxacin (Cipro) is taken as model drug that achieves release of 64.15 % in 32 h from β-Cipro@PAM/Dex/CQD hydrogels in acidic medium. From theoretical study, release rate constants, R2, Akaike information criterion (AIC) and model selection criterion (MSC) are computed to determine the best fitted kinetics model. Peppas-Sahlin model is the best fitted kinetics model for β-Cipro@PAM/Dex/CQD and concluded that the release of Cipro follows Fickian drug diffusion mechanism in acidic medium.

Improvement of biomedical properties of PEO-treated titanium with flurbiprofen and exosome conjugation

Exosome (EXO)-based drug delivery systems have attained a desirable position among scientific researchers and in biomedical applications. In this study, an exosomal coating comprising the anti-inflammatory drug flurbiprofen (FLB) was applied on a commercially pure titanium (cp-Ti) substrate that had undergone surface treatment using plasma electrolytic oxidation (PEO) process. The samples were characterized through field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and water contact angle (WCA) measurement. The results indicated that FLB was loaded onto the EXO and the formation of FLB.EXO was confirmed by FTIR, XRD, AFM and FESEM. Furthermore, FLB.EXO system was treated on PEO-treated substrates and FLB.EXO@PEO system demonstrated a considerable degree of roughness (Ra= 51.16 nm) and exceptional WCA (37.2 ± 0.7 ̊) in comparison to the other samples. The cellular inquiries were assessed through examination of the morphology of bone marrow mesenchymal stem cells (BMMSc) and the MTT assay. The cytotoxicity assessment showed that the FLB.EXO@PEO improved BMMSCs attachment without toxicity. The antibacterial efficacy was determined by means of bacterial adhesion testing against both gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) bacterial strains. FLB.EXO@PEO sample also revealed an excellent antibacterial rate of ∼ 86 % against S. aureus and ∼ 55 % against E. coli. Additionally, in vitro drug release evaluations indicated that sustained drug release was occurred and FLB released from FLB.EXO@PEO during 191 h that was lower than release time in FLB.EXO (120 h). Moreover, the prolonged release was confirmed by constant release rate in both of systems of FLB.EXO and FLB.EXO@PEO after 191 h and 167 h, respectively. The release kinetic of FLB.EXO and FLB.EXO@PEO followed the zero order and first-order model, respectively. Overall, the results indicate that the designed sustained release system have a high potential for development of advanced biomedical implants.

Macrophage-mediated controlled release of cysteine protease inhibitor from PLGA-PEG/hydroxyapatite microspheres for targeting cathepsin S in Alzheimer’s disease

The cause of Alzheimer’s disease (AD) remains unknown; however, studies have indicated the increased expression of cathepsin S (CTSS) in AD brains. Cathepsin S acts as a β-secretase, prompting the release of amyloid-β peptides and stimulating microglial cell activation, causing microglial migration, and contributing to neuroinflammation and disease progression. In this study, CT001, an inhibitor of the cysteine protease CTSS, was encapsulated in poly(lactic-co-glycolic acid)-polyethylene glycol microspheres combined with hydroxyapatite microspheres (CPPMs/HAMs) to achieve a constant and long-term drug release for AD. The results showed that CPPMs/HAMs had a uniform diameter of approximately 1 μm, enabling macrophage endocytosis and facilitating sustained CT001 release into the bloodstream, ultimately reaching the brain for AD treatment. The developed CPPMs/HAMs demonstrated excellent anti-inflammatory properties and mitigated CTSS expression in an in vitro inflammation microglial model. Intramuscular administration of CPPMs/HAMs improved learning and memory in AD mice during behavioral assessments. Furthermore, CPPMs/HAMs reduced CTSS expression, amyloid-beta accumulation, and deposition in vivo. This study demonstrated the potential of CT001 delivered via CPPMs/HAMs as a promising approach for managing AD in patients.

Tailoring drug release from long-acting contraceptive levonorgestrel intrauterine systems

The wide array of polydimethylsiloxane (PDMS) variants available on the market, coupled with the intricate combination of additives in silicone polymers, and the incomplete understanding of drug release behavior make formulation development of levonorgestrel intrauterine systems (LNG-IUSs) formidable. Accordingly, the objectives of this work were to investigate the impact of excipients on formulation attributes and in vitro performance of LNG-IUSs, elucidate drug release mechanisms, and thereby improve product understanding. LNG-IUSs with a wide range of additives and fillers were prepared, and in vitro drug release testing was conducted for up to 12 months. Incorporating various additives and/or fillers (silica, silicone resins, silicone oil, PEG, etc.) altered the crystallization kinetics of the crosslinked polymer, the viscosity, and the microstructure. In addition, drug-excipient interactions can occur. Interestingly, additives which increased matrix hydrophobicity and hindered PDMS crystallization facilitated dissolution and permeation of the lipophilic LNG. The influence of additives and lubricants on the mechanical properties of LNG-IUSs were also evaluated. PDMS chemical substitution and molecular weight were deemed to be most critical polymer attributes to the in vitro performance of LNG-IUSs. Drugs with varying physicochemical characteristics were used to prepare IUSs, modeling of the release kinetics was performed, and correlations between release properties and the various physicochemical attributes of the model drugs were established. Strong correlations between first order release rate constants and both drug solubility and Log P underpin the partition and diffusion-based release mechanisms in LNG-IUSs. This is the first comprehensive report to provide a mechanistic understanding of material-property-performance relationships for IUSs. This work offers an evidence-based approach to rational excipient selection and tailoring of drug release to achieve target daily release rates in vivo. The novel insights gained through this research could be helpful for supporting development of brand and generic IUS products as well as their regulatory assessment.

A finite crack growth energy release rate for interlaminar fracture analysis of composite material at different temperatures

The interlaminar fracture toughness of unidirectional fiber reinforced polymer composite material is temperature and crack growth history dependence. The non-constant interlaminar fracture toughness challenges the wide application of the linear elastic fracture mechanics-based approach for analyzing the interlaminar crack growth in composite material and structures. In addition, a quantitative relationship between the ductility of the matrix and interlaminar fracture toughness of the fiber reinforced composite is still highly desirable. In this paper, both pure resin and composite double cantilever beam (DCB) are tested at different temperatures. A finite crack growth energy release rate is used to analyze the interlaminar crack growth behavior of composite material at different temperatures. The plasticity of the composite DCB is modeled by Hill’s anisotropic plasticity, with the properties determined from multiscale analyses. It is found that a single constant finite growth energy release rate can well predict the interlaminar mode I crack growth of composite material at different temperatures. The roles of the ductility of matrix, thickness of the DCB, and crack growth history on the interlaminar mode I fracture toughness of composite material are quantitatively determined by using the present method.

Spectroscopic Determination and In vitro Bioequivalence Studies of Different Amoxicillin Capsule Brands

Amoxicillin is an aminopenicillin antibiotic, used in the treatment of several infections resulting from susceptible Gram-positive and Gram-negative, such as pneumonia, acute otitis media, acne vulgaris, bacterial endocarditis, streptococcal pharyngitis, urinary tract, Lyme borreliosis, Salmonella, Helicobacter pylori, chlamydia, and odontogenic infections. The study aimed to determine the in-vitro bioequivalence of amoxicillin capsules from various brands using physicochemical and spectroscopic parameters. Weight uniformity, friability, disintegration, dissolving tests, and UV spectroscopy were used to determine the in-vitro bioequivalence of different brands of amoxicillin capsules. The weight variation for all the capsules showed compliance with the USP specifications (≤10% weight deviation). All brands complied with the USP/BP specification for the disintegration test, as disintegration time ranged from 7 to 12 minutes. The dissolution profile of the innovator and the generic brands showed a percentage release from 80.81 – 89.11% within 30 minutes. The first-order kinetics, t1/2 and k of amoxicillin released ranged from 16.01 – 27.11 min and 2.56 – 4.33 x 10-2 min-1 respectively. A straight-line graph was obtained as a calibration curve of amoxicillin. UV absorption spectrum showed four distinctive peaks at 240, 275, 320, and 360 nm, with the maximum at 240 nm, while the percentage content of amoxicillin ranged from 90.58 ± 1.38 to 98.74 ± 0.97%. This result complied with the BP and USP specifications. Hence, there was a strong correlation between the release rate constant, k, and time since values were ≥ 0.8087 compared with the innovator and other brands.

Synthesis and Characterization of Cassava Gum Hydrogel Associated with Chlorhexidine and Evaluation of Release and Antimicrobial Activity.

Hydrogels from natural sources are attracting increasing interest due to their ability to protect biologically active molecules. Starch extracted from cassava tubers is a promising material for synthesizing these hydrogels. Copolymerization of cassava gum and incorporation of chlorhexidine digluconate (CLX) into the hydrogels is confirmed by changes in the crystallographic profile, as observed through X-ray diffraction, and a shift in the 1000 cm-1 band in the Fourier-transform infrared spectroscopy spectrum. The differential scanning calorimetry reveals changes in the decomposition temperature of the synthesized hydrogels related to CLX volatility. Micrographs illustrate the material's porosity. Release tests indicate a constant linear release over 72 h, while antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans is satisfactory, with 100% effectiveness from 0.5% CLX and the formation of inhibition halos. Toxicity and biocompatibility studies show no cytotoxicity. The continuous release of chlorhexidine is promising for components of biomedical implants and applications as it can ensure antimicrobial action according to specific therapeutic needs.

Depth-Wise Distribution of Soil Chemical Properties, Micro-nutrients Status, and Bacterial Population under Quercus leucotrichophora and Shorea robusta Forest of Chakrata and Thano Region of Uttarakhand

Forest trees have an appreciable demand for nutrients as they have longer rotation than crops and this is easily replenished by the constant release of nutrients resulting from weathering under favorable conditions in the soils developed from parent material rich in nutrient-bearing minerals. A study was undertaken to assess the chemical properties, micro-nutrient status, and bacterial population; two sites were taken for the collection of soil samples: the oak forest of Chakrata and the Sal forest of Thano. Soils were drawn at three depths viz. 0-30 cm, 30-60 cm, 60-90 cm. All soil parameters examined at three depths viz. 0-30 cm, 30-60 cm, 60-90 cm. Oak (Quercus Leucotrichophora) forests have higher microbial activity than Sal forests. The soil in both the studied areas was rich in nutrients, where, the maximum mean standard deviation values of pH (6.85), soil organic carbon (5.9 %), available nitrogen (0.04 %) reported in the Oak forest of Chakrata, and available phosphorus were almost similar in both forest regions. Oak forests have higher organic carbon, water-holding capacity, and nutrient availability compared to Sal forests. However, it is concluded that, for better conditions of these forests for soil and carbon-storing potential, the forest needs good management practices, especially in community forest areas to avoid illegal felling, impact of fire, and over-exploitation of fuel and fodder. Good management practices would help mitigate the impact of climate change and sustainable outcomes of the resources for the community's benefit.

A multifunctional composite hydrogel that sequentially modulates the process of bone healing and guides the repair of bone defects

Calcium carbonate (CaCO3), which exhibits excellent biocompatibility and bioactivity, is a well-established bone filling material for bone defects. Here, we synthesized CaCO3 microspheres (CMs) to use as an intelligent carrier to load bone morphogenetic protein-2 (BMP-2). Subsequently, drug-loaded CMs and catalase (CAT) were added to methacrylated gelatin (GelMA) hydrogels to prepare a composite hydrogel for differential release of the drugs. CAT inside hydrogels was released with a fast rate to eliminate H2O2 and generate oxygen. Constant BMP-2 release from CMs induced rapid osteogenesis. Results in vitro indicated that the composite hydrogels efficiently reduced the level of intracellular reactive oxygen species, preventing cells from being injured by oxidative stress, promoting cell survival and proliferation, and enhancing osteogenesis. Furthermore, animal experiments demonstrated that the composite hydrogels were able to inhibit the inflammatory response, regulate macrophage polarization, and facilitate the healing of bone defects. These findings indicate that a multi-pronged strategy is greatly expected to promote the bone healing by modulating pathological microenvironments.

Alginate-coated pomelo pith cellulose matrix for probiotic encapsulation and controlled release

A novel carrier comprised of ethanol- and alkali-modified cellulosic pomelo pith matrix coated with alginate was developed to improve viability while enabling gastrointestinal release of probiotics. Scanning electron microscopy imaging revealed the agricultural byproduct had a honeycomb-structured cellulose framework, enabling high loading capacity of the probiotic Lactobacillus plantarum up to 9 log CFU/g. Ethanol treatment opened up pores with an average diameter of 97 μm, while alkali treatment increased swelling and porosity, with an average pore size of 51 μm. The survival rate through the stomach was increased from 89.76 % to 91.08 % and 91.24 % after ethanol and alkali modification, respectively. The control group displayed minimal release in the first 4 h followed by a burst release. Both ethanol modification and alkali modification resulted in constant linear release over time. The release time was prolonged when decreasing the width of the pomelo peel rolls from 10 mm to 5 mm while keeping the volume of the peel constant. After 8 weeks of refrigerated storage, the cellulose-encapsulated probiotics retained viability above 7 log CFU/g. This study demonstrates the potential of the structurally intact, sustainably-sourced cellulosic pomelo pith for probiotic encapsulation and controlled delivery.

Development and characterization of a novel bigel system based on candelilla wax oleogel and guar gum hydrogel for heat-triggered release properties

This study introduces an innovative approach for the encapsulation and heat-triggered release of natural pigment, paprika oleoresin (PO) as a model pigment, by formulating oleogel-in-hydrogel bigels incorporating candelilla wax (CW). By varying the CW concentrations, the impact on the critical physicochemical properties of bigels was investigated. Increasing CW concentration from 2 to 8% elevated the sol-gel transition temperature (Tg) of the oleogels significantly, ranging from 45.83 ± 0.83 to 61.38 ± 0.51 °C (p < 0.05). Across all CW concentrations, high encapsulation efficiency over 95% was consistently observed. Conversely, reducing CW concentration increased droplet size within the bigels, varying from 13.19 ± 2.97 to 2.97 ± 0.60 μm (p < 0.05). Notably, these bigels exhibited distinct heat-triggered pigment release characteristics. In specific, the amount of released PO decreased with increased CW concentration, resulting in a lower ΔE* value. Correlation analysis highlighted CW's positive correlation with the Tg of the oleogel and bigel lightness, and its negative correlation with droplet size, cumulative pigment release content, release rate constant, redness, yellowness, and ΔE* of the bigel. These results indicate that controlling pigment release through CW-based bigels with thermoresponsive properties can enhance color stability and preserve the integrity of pigment during heat processing. This novel bigel system with heat-triggered release properties holds promise for wider application in the food industry. Overall, it addresses the critical need to stabilize and precisely regulate natural pigment release, which is important for both product quality and consumer satisfaction in the food industry.

Benzodiazepine Interference with Fertility and Embryo Development: A Preliminary Survey in the Sea Urchin Paracentrotus lividus.

Psychotropic drugs and benzodiazepines are nowadays among the primary substances of abuse. This results in a large and constant release into aquatic environments where they have potentially harmful effects on non-target organisms and, eventually, human health. In the last decades, evidence has been collected on the possible interference of benzodiazepines with reproductive processes, but data are few and incomplete. In this study, the possible negative influence of delorazepam on fertilization and embryo development has been tested in Paracentrotus lividus, a key model organism in studies of reproduction and embryonic development. Sperm, eggs, or fertilized eggs have been exposed to delorazepam at three concentrations: 1 μg/L (environmentally realistic), 5 μg/L, and 10 μg/L. Results indicate that delorazepam reduces the fertilizing capacity of male and female gametes and interferes with fertilization and embryo development. Exposure causes anatomical anomalies in plutei, accelerates/delays development, and alters the presence and distribution of glycoconjugates such as N-Acetyl-glucosamine, α-linked fucose, and α-linked mannose in both morulae and plutei. These results should attract attention to the reproductive fitness of aquatic species exposed to benzodiazepines and pave the way for further investigation of the effects they may exert on human fertility. The presence of benzodiazepines in the aquatic environment raises concerns about the reproductive well-being of aquatic species. Additionally, it prompts worries regarding potential impacts on human fertility due to the excessive use of anxiolytics.

Enhancing the durability and antibacterial activity of glass ionomer restorative material enriched by l-arginine and nano-titanium for pit and fissure sealing

BackgroundSealing teeth’ pits and fissures is of prime importance in preventing caries. Despite the evidenced bioactivity of glass-ionomer cements (GICs), they still fail to totally inhibit caries. This partially might be due to their insufficient antibacterial and strength properties. l-arginine (Arg) has superior caries-preventive potential thanks to its prebiotic-based biofilm-modulating effect. Titanium dioxide (TiO2) on the other hand, has well-known antibacterial characteristics, and being in nano size is supposed to improve strength. Therefore, this study aims to improve the antibacterial efficiency and the mechanical properties of conventional GICs using 1% Arg and 3% TiO2 nanoparticles for pit and fissure sealing.MethodsEtched enamel surfaces of 100 extracted human third molars were randomly divided into two groups; a control group, where teeth were restored using glass ionomer Ionofil Plus, and an experiment group, where teeth were restored using glass ionomer Ionofil Plus incorporating Arg–TiO2. Specimens of both groups were tested for microleakage, enamel shear bond strength, and fluoride ion release using a stereo microscope, universal testing machine, and ion chromatography ICs 5000+ SP respectively. Surface analysis was conducted through scanning electron microscopy coupled with energy-dispersive X-ray analysis (SEM–EDX) and atomic force microscope (AFM). Furthermore, specimens of both groups were incubated with Streptococcus mutans, Lacticaseibacillus rhamnosus, and Actinomyces viscous for quantitative antibacterial evaluation, compared to a specimen-free control using adherent/planktonic bacterial count test.ResultsThe experimental group had statistically lower microleakage percentage, higher shear bond strength, and constant fluoride release compared to the control group at P = 0.01, 0.002, and < 0.001 respectively. SEM of the experimental group revealed hybrid particles of the Arg–TiO2 incorporating GIC with clusters of uniformly distributed TiO2 nanoparticles. AFM showed lower surface roughness for the experimental group indicating its homogeneity. The adherent probiotic L. rhamnosus bacterial count had the highest count in Arg–TiO2 (IP) GIC group (P < 0.001) with lack of adherent pathogenic S. mutans bacterial count compared to planktonic/adherent S. mutans bacterial count in the control group and (IP) GIC group (P < 0.05).ConclusionsIncorporating 3% TiO2 nanoparticles and 1% Arg in GICs can enhance their mechanical properties, fluoride release, and antimicrobial efficiency.

Performance-Based Design Assessment of Temperature Tenability Condition in a Hotel Atrium

Fire safety risk assessment to prevent loss of human life and property is necessary for complex structures where the traditional prescriptive designs are inapplicable. Maintaining tenable temperature conditions is essential for the safe evacuation of building occupants. This study considered British Standards (BS) 7974 and the Code of Practice for Fire Precautions in Buildings to analyze the temperature tenability conditions in the hotel atrium through a performance-based design approach. Further, the Computational Fluid Dynamics (CFD) code, Pyrosim, a Graphical User Interface (GUI) of the Fire Dynamics Simulator (FDS), was utilized to simulate a constant Heat Release Rate (HRR) steady state design fire of 5 Megawatts (MW) igniting from the hotel brasserie (ground floor) within the atrium. The researcher used the big design fire of 5MW to generalize the results to similar fires in similar structures. The objective was to conduct a fire safety risk assessment to prevent loss of property and fatalities by activating a smoke management control system with a ‘what if’ condition when the fire suppression system failed to start. Temperature data was collected through the statistical steady state profile, smoke layer temperatures, thermocouples, and 2-dimensional slice temperature recordings. The ground floor, the fire source, was found to have untenable conditions for human survival with temperatures above 2250C, as confirmed by thermocouple and steady-state temperature profile readings. Other floors demonstrated tenable conditions for human survival with temperatures below 400C due to the effect of natural vents and mechanical extractors, which extracted the hot smoke at a rate of 15m/s. The temperature recordings from this study compared well with those from Chew and Liew’s (2000) Computational Fluid Dynamics results, which had fire igniting within the atrium, without sprinklers, and had mechanical extraction fans and a constant Heat Release Rate of 5 Megawatts (MW). The results indicated that the smoke control management system maintained tenable temperature conditions within the hotel atrium, even without the fire suppression system through sprinklers. Considering the design fire size was 5 MW, which was significantly big, the results could be generalized for other hotels or structures with similar designs.

The reproduction number and its probability distribution for stochastic viral dynamics.

We consider stochastic models of individual infected cells. The reproduction number, R, is understood as a random variable representing the number of new cells infected by one initial infected cell in an otherwise susceptible (target cell) population. Variability in R results partly from heterogeneity in the viral burst size (the number of viral progeny generated from an infected cell during its lifetime), which depends on the distribution of cellular lifetimes and on the mechanism of virion release. We analyse viral dynamics models with an eclipse phase: the period of time after a cell is infected but before it is capable of releasing virions. The duration of the eclipse, or the subsequent infectious, phase is non-exponential, but composed of stages. We derive the probability distribution of the reproduction number for these viral dynamics models, and show it is a negative binomial distribution in the case of constant viral release from infectious cells, and under the assumption of an excess of target cells. In a deterministic model, the ultimate in-host establishment or extinction of the viral infection depends entirely on whether the mean reproduction number is greater than, or less than, one, respectively. Here, the probability of extinction is determined by the probability distribution of R, not simply its mean value. In particular, we show that in some cases the probability of infection is not an increasing function of the mean reproduction number.