Background: Antibiotic resistance is a global health crisis. The aim of this study was to explore dentists’ perceptions of antibiotic resistance. Methods: A qualitative method was used. Seventeen dentists practising in the Nancy  region were surveyed. They were general practitioners or specialised in oral surgery, implantology, or periodontology. The practitioners took part in semi-structured interviews between September 2019 and July 2020. All of the interviews were transcribed in full and analysed thematically. Results: Four major themes have been selected: attitudes of the dentists in regard to the guidelines, clinical factors that influence prescriptions, non-clinical factors that influence prescriptions, and the perception of antibiotic resistance. The dentists stated that they were very concerned regarding the public health issue of antibiotic resistance. However, they often prescribe according to their own interests and habits rather than according to the relevant guidelines. Conclusions: Although dentists are generally well aware of antibiotic resistance, they often do not adequately appreciate the link between their prescribing habits and the phenomenon of antibiotic resistance. Regular updating of practitioners’ knowledge in this regard is necessary, but patients and the general public should also be made more aware of the issue. Antibiotic resistance represents a global public health crisis that has the potential to lead to numerous morbidities and increased mortality in the next 10 years due to the emergence of multi-resistant strains . RepeateIn France, antibiotics are mainly prescribed for outpatients (93%), and general practitioners are responsible for 70% of all antibiotic prescriptions . DentistNumerous global , EuropeaIt is not currently known to what extent French dentists are aware of antibiotic resistance. For those who are, it is not known how they perceive their share of responsibility in this phenomenon.The aim of this study was to explore dentists’ perceptions of antibiotic resistance. To do this, dental practitioners’ use of antibiotics and their position regarding the guidelines for antibiotic prescription were studied.Twenty of the 40 dentists who were contacted agreed to participate in the study. The interviews took place between September 2019 and July 2020. The interviews were discontinued after 17 encounters as data saturation was reached. The characteristics of the dentists interviewed are summarised in More than half of the practitioners (13/17) were supportive of the antibiotic prescription guidelines, and they stated that they used them in their practice. Nevertheless, some of the practitioners expressed the opinion that the recommendations sometimes do not adequately take into account the clinical reality (P9). The three practitioners who had a university hospital practice in addition to their private practice stated that this aspect of their practice provided them with a source of information and allowed them to remain informed (P8).It’s a consensus of college professors who don’t practice. I’m sorry, it’s not to say that I am unaware of the issues …”“P9Honestly, if I wasn’t in the hospital, I wouldn’t have done any…well…I don’t think I would have known about it”“P8The majority of the implant practitioners (8/9) reported that they routinely prescribe antibiotics during their surgeries and they claimed to be aware of the guidelines. They justified their prescriptions by a desire to prevent adverse effects from infection or even to reassure themselves. All of the dentists practising implantology prescribed a 7-day course of antibiotics, except for one dentist who recommended antibiotic prophylaxis before the procedure (P13).It’s true that empirically, I haven’t seen any significant difference after surgery with or without antibiotics. But for my own peace of mind, I like to give them a dose of antibiotics beforehand anyway”“P13More than half of the practitioners (11/17) felt that there was a degree of discrepancy between the guidelines and the actual prescriptions issued by the dentists. However, not all of the dentists interviewed (4/17) considered themselves as being responsible for this discrepancy. The main reason given for the discrepancy in their professional environment was the lack of information and training regarding the guidelines. This, they said, was either because information about the guidelines was buried among other information or had to be searched for in order to obtain it (P9). Amoxicillin was the antibiotic of choice for most of the practitioners. This drug was sometimes even considered not to be a potential source of antibiotic resistance (P17). However, the combination of spiramycin and metronidazole was a source of disagreement. While some considered this association to be obsolete and ineffective, most of the practitioners still used it in their practice, sometimes even describing it as indispensable to the profession (P9).There should be regular reminders. Because when the recommendations were made, I didn’t hear anything about them. It’s not a subject that interests me when I go to a conference”“P9I don’t feel like I have a very harmful role in terms of public health, just by prescribing amoxicillin”“P17®  we have fewer good results, but I sometimes give it because it’s quite well-tolerated, and it is a way to provide metronidazoleWith Birodogyl”“P9All of the practitioners referred to how antibiotic prescriptions are necessary in their daily practice in order to prevent or treat infections. They all reported taking into account the risks associated with certain treatments, such as bisphosphonates, radiation therapy, or cancer chemotherapy, as well as the risks associated with chronic illnesses. Some practitioners tended to routinely prescribe antibiotics to prevent complications (P9). Others readily referred patients to the hospital when they perceived them to be at high risk, as they did not feel confident enough to manage these cases and their potential complications (P11). Finally, some dentists instead sought the advice of the general practitioner or the specialist in charge of the patient to make a decision.I find it more difficult than before, because in some cardiology protocols you now have to give antibiotics, in others you don’t have to. So, I tend to give them systematically when people are at risk ok bacterial diffusion”“P9Uh… (lowered voice) I address. […] yes, because it’s not so much that we don’t know how what is involved, it’s that we ultimately have to manage the complications, and in private practice, we don’t have the means to manage it, in any case, they don’t give them to us”“P11The majority of the practitioners admitted that they sometimes prescribe antibiotics for their own peace of mind. Indeed, they tended to prescribe an antibiotic in case of doubt (P8), to prevent possible complications following treatments , or out of fear of negative feedback or even medico-legal action (P17). At times, they were able to prescribe antibiotics in cases where they were not indicated but the patients requested them. Lack of time, often in the context of emergency situations, tended to result in relatively frequent prescription of antibiotics. In addition, the prescription of antibiotics was sometimes thought to be warranted for patients who were managed just before the weekend or before going on vacation (P14). More personal factors could influence what the dentists prescribed, such as their family and friends or their habits. Their clinical experience, or even significant one-off experiences, tended to result in new prescribing habits. Some of the younger dentists considered that older practitioners tended to overprescribe antibiotics (P4).Most of the participants felt that the patients had a pronounced influence on what they prescribed. A few dentists stated that they prescribe antibiotics for the sake of patient comfort, their “psychological need”, or to reassure their patients, particularly in case of patients who they considered to be very demanding and insistent (P1). Others claimed that the patient’s age was a factor and they tended to prescribe more antibiotics for older or very young patients. One practitioner felt that young patients did not always adhere to prescription durations and they, therefore, tended to prescribe antibiotics for relatively short durations.For some people, for peace of mind, you put down 6 days of amoxicillin. That’s not going to create resistance and then at least I’m off the hook”“P8In France, we have this notion that in all cases we must take precautions, and that if you have prescribed antibiotics, then you can’t be blamed for not having given any”“P17On Fridays, I’m going to do it all day long because, if there is a chance of a problem, I want to prevent it from happening. I don’t want the guy to have to go back to the dentist who is on call to get a prescription, so it depends a bit on the day of the week”“P14When all is said and done, I think we are still part of the generation where we already know that antibiotics are no longer a silver bullet. Unlike the generation that preceded us, for whom antibiotics were a novelty and a marvelous invention that could seemingly cure anything”“P4I’m going to reserve it for the patients who are difficult (laughs), patients who don’t let up; then -in case of any doubt- I usually throw in some antibiotics, anti-inflammatories, and analgesic so that they stop bothering me”“P1The main idea highlighted was a sense of awareness regarding antibiotic resistance, despite a lack of clinical hindsight and direct confrontation of participants in their practice (P15). A majority of practitioners acknowledged that dentists were also implicated to a certain extent in the phenomenon of antibiotic resistance, but they nonetheless did not believe that they played a major role in this phenomenon (P2). Despite this general concern, the participants did not feel that they were sufficiently informed regarding the subject, as they felt that the subject was not sufficiently discussed either in training courses or in professional journals.A few dentists felt that patients have a large degree of responsibility, particularly in terms of non-compliance or sometimes even self-medication (P3). According to some of the practitioners, this was due to the lack of understanding among patients, i.e., a lack of knowledge regarding antibiotics and the phenomenon of antibiotic resistance. A collective increased awareness of patients was thought to be necessary (P10). One practitioner said that dentists even have a role in informing patients about the misuse of antibiotics.While the dentists acknowledged that they have a degree of responsibility in regard to the development of antibiotic resistance, many of the participants identified physicians as being the main culprits, particularly general practitioners. Indeed, they were often reproached for prescribing antibiotics in cases where it was not indicated or involved unsuitable drugs (P13). According to a number of the dentists (P6), hospital medicine, particularly the emergency services, also shared some of the responsibility Some of the participants suggested that pharmacists were also involved in this phenomenon, as the pharmacists’ advice to patients sometimes was not in keeping with their prescriptions (P8).So, it’s true that I feel a little far removed from that, even though I know that it’s a notion that exists, that is proven, that it’s been demonstrated that there is resistance, but it’s true that I feel…yeah, really quite far removed from that”“P15Oh well, no, I think that we, as dentists, have a fabulous impact on reducing resistance in general, I don’t think we are the ones to blame”“P2Some people self-medicate or stop treatment, and this leads to antibiotic resistance”“P3I don’t think patients are aware of this. I think details regarding the medication are a little bit overwhelming for them. Most of them don’t even know why they’re taking antibiotics. So, from there to understanding antibiotic resistance…”“P10® , systematically.But it’s true that the typical doctor’s prescription when it comes to teeth is to prescribe NSAIDs  and Birodogyl”“P13In my opinion, it’s more in general medicine and even in the hospital. How many people go to the emergency room and get antibiotics because they have a toothache?”“P6(speaking of pharmacists) “They put ideas into the heads of patients who are already lacking confidence”P8Dentists have a significant role to play in the fight against antibiotic resistance, not only because of the number of prescriptions that they issue but also because of their relevance. This work, which to our knowledge is the first of its kind in France, highlights a number of previously undescribed non-clinical factors that influence the prescription of antibiotics. It also reveals how French dentists perceive antibiotic resistance.An antibiotic prescription needs to be justified by the existence of an infection, identifiable by specific clinical signs, or for prevention during certain high-risk procedures, particularly in patients who are in poor health . HoweverA discrepancy between the statements regarding the knowledge of the current French guidelines and their applications has already been highlighted in a recent article . The praThe current situation is reason for concern. Indeed, dentists are not sufficiently aware and sensitised to antibiotic resistance. They acknowledge having a degree of involvement in the development of this phenomenon, but they maintain that other health professionals, particularly general practitioners, are the main party responsible. This was already highlighted in a similar study conducted in the UK in 2014 .Antimicrobial resistance is a non-palpable phenomenon that dentists as well as other health professionals, who think that they do not personally encounter it in their daily practice, find hard to fathom. This is probably the root cause of the difficulties with the implementation of effective means of combatting antibiotic resistance in dental surgery as well as in other health professions. Dental surgeons would also benefit from improvement of their initial and postgraduate training. They also need easy access to information and new recommendations when they are published. However, informing patients regarding antimicrobial resistance and the scarcity of real needs for antibiotic prescriptions in dentistry is also essential in order to raise individual and collective awareness ,20.Amoxicillin is the antibiotic most prescribed by dentists in France, with 20% of their prescriptions being for this antibiotic . We haveThis work has many strengths. Although there have been many qualitative studies at the national ,23 and iHowever, this study has certain limitations. Indeed, a desirability toward bias may exist in the responses of the participants, who could sometimes have provided answers according to what seemed acceptable to them rather than according to their own habits, as well as in their interpretation of the questions. A selection bias is inevitably present because the participation was voluntary. Indeed, there were no rural dentists who volunteered to participate in this study. However, we have no reason to believe that their answers would have been fundamentally different from the others. As many clinical and non-clinical factors that influence antibiotic prescriptions by dentists have been mentioned, it would seem relevant to further study these factors in a thorough and exhaustive manner.This study reflects the perceptions of a diverse sampling of dentists that involved different genders, ages, practices, and modes of practice, but it—like all qualitative research—is not intended to be a representative panel of French dentists.A qualitative study, based on semi-structured interviews, was chosen to achieve the main objective. Initially, the interview script was structured into two main themes: antibiotics and antibiotic resistance. The construction of this script and the formulation of the questions were based on similar studies conducted in general medicine ,28 and dThe target population of the study was dentists who were in private practice at the time of recruitment (excluding private replacements), as this is the main mode of practice in France . The conThe interviews were conducted face-to-face while the participants were on their own at their respective workplaces. Two researchers (J.D. and M.-O.V.) conducted the interviews. The first researcher interviewed the practitioner and the second researcher acted as an observer, refocusing the interview if necessary. The interviews were conducted with the consent of each participant. The practitioners did not receive any financial compensation for participation. All of the interviews were recorded and transcribed verbatim. Laughter, hesitation, and the facial expressions of each participant were noted. After the transcriptions, a floating reading of the interviews was carried out separately by the two researchers in order to extract verbatim comments. The verbatims were then pooled in order to build a first analysis grid, which was rectified and then further developed after a second reading. Four major themes were selected: position in relation to the guidelines, clinical factors that influence prescriptions, non-clinical factors that influence prescriptions, and the perception of antibiotic resistance by the dentists. A third reading led to final modifications of the grid and then to a horizontal followed by a vertical analysis with a triangulation of the data .The qualitative research methodology complied with the international Consolidated Criteria for Reporting Qualitative Research (COREQ).Dentists are aware of the phenomenon of antibiotic resistance, but they do not appear to appreciate the link between their prescribing habits and the occurrence of bacterial resistance to antibiotics. The factors that influence their prescriptions are numerous, and initial and continuing education alone cannot change their practices.Nevertheless, there is a real need for regular updating of knowledge. While practitioners are generally amenable to training regarding the guidelines of good practice, these guidelines also require broad and clear channels of dissemination. However, changing behaviours is a complex science, as demonstrated in the work of Michie et al. Indeed, many factors, that are often difficult to take into account, can influence practitioners’ decision making and trigger prescribing. The evaluation of a framework after its implementation is therefore crucial in order to judge the effectiveness of the proposed method, if we hope to change practitioners’ behaviour regarding antibiotic prescriptions .The complexity of the phenomenon of antibiotic resistance and the diversity of the parties involved in its occurrence  highlight the need for further studies. The need for training and information expressed by dentists is associated with a requirement for the involvement of other parties, particularly patients, in raising awareness of antibiotic resistance. Various approaches could be explored, such as the implementation of new campaigns for the general public or the development of explanatory leaflets provided by prescribing practitioners or pharmacists.


This could cause an indirect reduction in energy usage and total expenses in the concrete industry. However, due to the uncertainties and irregularities in size, shape, and chemical compositions, some nanosized materials might have harmful effects on the environment and human health. Acknowledgement of the possible beneficial impacts and inadvertent dangers of these nanosized materials to the environment will be extremely important when pursuing progress in the upcoming years. This research paper is expected to bring proper attention to the probable effects of construction waste, together with the importance of proper regulations, on the final disposal of the construction waste.At present, nanotechnology is a significant research area in different countries, owing to its immense ability along with its economic impact. Nanotechnology is the scientific study, development, manufacturing, and processing of structures and materials on a nanoscale level. It has tremendous application in different industries such as construction. This study discusses the various progressive uses of nanomaterials in concrete, as well as their related health risks and environmental impacts. Nanomaterials such as nanosilica, nano-TiO Nanotechnology is a developing field of science related to the engineering of nanosized particles composed of different materials ,3,4,5,6.In the past several decades, nanotechnology has accomplished incredible development ,12,13,14The chemistry and physics of nanosized construction materials vary from ordinary materials because of quantic effects and a greater surface-area-to-volume ratio. Characteristic morphologies of nanomaterials are sheets, cylinders, and spheres. Currently, the utilization of nanomaterials in the building and construction materials industries has highlighted several benefits ,32,33,34Concrete is one of the prominent materials in building industries. Concrete is a mixture of aggregates and paste . The aggCement manufacturers mine materials such as iron ore, shale, limestone, and clay; crush and screen the rock; and place it inside a cement kiln. After heating at higher temperatures, these materials will form a tiny ball termed as a “clinker”, which is extremely fine-ground to prepare Portland cement. Silica and lime make up about 85% of the cement ingredients. Other elements present are iron oxide and alumina . PlasticDespite such progress in nanotechnology, proper information regarding nanomaterials’ environmental and human health impacts has been insufficient until now ,54,55,56In the present study, we analyzed the use of nanomaterials in the prominent concrete sector field in the construction industries. The evolution of the number of publications related to the nanomaterials in concrete sector is presented in An important challenge associated with the concrete sector is the decrease in the emissions of carbon dioxide gas. A solution to the aforementioned problem is the development of concrete frameworks with improved mechanical properties and enhanced durability, which would in turn reduce the maintenance needs and also reduce the requirement for early replacements. However, we also must consider the risk assessment, health issues due to the exposure of nanomaterials, and environmental implications associated with the application of nanomaterial-based concrete structures. The above mentioned positive and negative factors were the main motivation of the current study. We attempted to analyze whether the inclusion of nanomaterials in concrete structures would improve the mechanical properties , ductility, freeze–thaw resistance, and abrasion resistance of the concrete. We selected the nanomaterials  presented here based on the articles we obtained from the Scopus database for concrete application. Moreover, in the current study, we sought to analyze whether the inclusion of carbon nanotubes and titanium dioxide in concrete could offer self-sensing and self-cleaning properties to the concrete structures. Furthermore, we also analyzed the challenges and limitations of the application of nanomaterials in the concrete sector. The amount of manufactured nanomaterials continues to grow at an exponential speed, and conventional toxicity approaches cannot keep up with the total number of nanobased materials employed in the construction sector. Thus, in our study, the risk evaluation, health issues due to nanomaterial exposure, and environmental implications related to the application of the construction field nanomaterials were comprehensively examined. The important features to be examined and discussed include a toxicological analysis, long-/short-term exposure dangers of nanomaterials to the health of humans and environment in the service life of the material, and the dangers related to nanomaterial disposal.To the best of our knowledge, studies on the up-to-date progress in nanotechnology for the application in concrete are still very limited. There is no study reported so far that collectively discussed the application of nanomaterials in the concrete sector, together with the challenges and limitations, the concrete recycling trend, risk assessment, health issues related to nanomaterials in concrete, and related environmental implications. This kind of study might be very beneficial to the appropriate development of applications and research interest toward additional progress in nanomaterials. This study aimed to contribute a comprehensive view of nanomaterials employed in the concrete sector and their possible toxicological implications. We understand that this study can contribute new knowledge as well as insights for the technical community in the concrete sector. The new and improved concrete structures with improved mechanical properties and enhanced durability can in turn reduce the maintenance needs and also reduce the requirement for early replacements. This research paper is expected to bring proper attention to the probable effects of construction waste, together with the importance of proper regulations, on the final disposal of the construction waste.Nanomaterials can be categorized according to their dimensions and size . There aEngineered nanoparticles are developed through either a bottom-up approach or a top-down approach. The two approaches vary such that in the top-down preparation approach, larger structures will be gradually reduced in size to nanometer dimensions, whereas the bottom-up preparation approach involves developing nanoparticles with individual atoms or molecules until the required size is accomplished. Additional categorization can be made depending on the mechanism of the preparation process, classifying most engineered nanomaterials into three categories: physical, mechanical, and chemical processes. Nanosilica is a nanomaterial commonly used in the concrete application, and has characteristics such as smaller particle sizes, good dispersion, high chemical purity, large surface energy, stronger surface adsorption, and large specific surface area . Various2) nanoparticles have been used for concrete application, and they have been prepared using different methods such as electrochemical synthesis [2 nanoparticles helps to absorb a large quantity of water, leading to a reduction in the concrete’s workability [Recently, titanium dioxide  and Cognoscible Technologies (Chile) for substituting silica fume in ready-mixed concrete amenities certified by the ISO 14001-Environmental Management System . This prSeveral studies have confirmed that carbon nanotubes in a lab environment can be used to improve the strength of materials and to contribute electrical conductivity . NanomatPresently, carbon nanotubes are also added to concrete as a nanofiller because they possess a higher surface area and unusual mechanical characteristics. Mohsen et al.  examinedLushnikova et al.  analyzedUltrahigh-performance concrete shows increased crack resistance and durability, with 150 MPa compressive strength, and thus it could be employed for the construction of facilities requiring adequate physical protection. CNT incorporation in ultrahigh-performance concrete was examined by Jung et al.  with resThus, it was noted that the carbon nanotubes were nanomaterials that could improve the concrete’s mechanical properties such as compressive strength, flexural strength, and ductility, and also offered crack resistance and increased electrical conductivity. The carbon nanotube application can increase the concrete beam ductility by approximately 150%. Moreover, the compressive strength of lightweight concrete specimens can also be increased by including CNTs. For improving the different properties of cement-based composites by the addition of CNTs, the appropriate dispersion of CNTs must be confirmed for the manufacture of CNT-containing cement-based composites. The knowledge of the chemical–mechanical dispersion mechanism of CNTs in cement-based composites is definitely beneficial in the design of CNT-containing functional cement-based composites. Various dispersion techniques, such as ultrasonication, use of admixtures or siliceous materials, minimization of the water-to-cement ratio, and modification of CNTs, have been attempted to disperse CNT particles in cementitious composites. The admixed carbon nanotubes could also reduce the porosity of the cementitious matrix. Furthermore, CNT incorporation into concrete can result in a decrease in both the early and long-term shrinkage of concrete.2 is manufactured in great quantities due to its photocatalytic, stable, and anticorrosive properties. The photocatalytic ability of titanium dioxide results from the higher surface area of the nanoparticles; thus, when incorporated in concrete, the material turns out to be self-disinfecting and self-cleaning. In the presence of light, the aforementioned nanomaterial disintegrates the dirt and organic pollutants present on the concrete surface into carbon dioxide and water; the catalytic reaction products are then simply detached by rain or simple cleaning. The addition of nano-TiO2 in cement matrices can offer concrete frameworks with self-sensing and self-cleaning capabilities. Zanfir et al. [2 photocatalytic nanoparticles. It was noted that the TiO2–silica fume composite powders demonstrated an improved pozzolanic activity and could be employed for the partial replacement of Portland cement in the self-cleaning mortar preparation. In a research work by Nikbin et al. [2 nanoparticles, substituted by weight of cement in different temperatures cycles. The test results confirmed that samples with 6% TiO2 nanoparticles met the design requirements (increased compressive strength).Another nanomaterial used in concrete is titanium dioxide. The inclusion of titanium dioxide in concrete can offer concrete some self-cleaning ability. Titanium dioxide-incorporated concrete can permit a photocatalytic degradation of contaminants from automobile and industrial emissions. TiOr et al.  studied n et al. , the gro2 nanoparticles, alumina nanoparticles, and nano-ferric oxide, on a self-consolidating concrete’s performance regarding durability and mechanical properties by performing various experiments. Self-consolidating concrete is a concrete type that can be placed, as well as compacted under its own weight, with no requirement for compaction. The Jubilee Church in Rome, Italy, which was constructed in 2003, was one of the first buildings that employed reinforced and self-cleaning concrete . The con2 in cement matrices could offer concrete frameworks with self-sensing as well as self-cleaning capabilities. It could also contribute improved mechanical properties, such as the compressive strength and durability, to the concrete. Moreover, incorporation of nano-TiO2 to the concrete mix could moderately reduce the V-funnel time, thereby confirming the improvement in the flowability property of self-consolidating concrete. The TiO2 nanoparticles also improved the strength and the durability of the nano-based concretes by enhancing the carbonization tolerance, as well as the resistance to different chemical attacks, which was additionally due to the upgrading in the microstructures, porosity reduction, and refinement of the voids or microcracks. The larger surface area and stronger reactivity of the nanoparticles added into the concrete structures could improve the pozzlanic reactions, leading to a significant improvement in strength performance.From the analysis of different studies, it was observed that the incorporation of nano-TiOThe optimum incorporation of ferric oxide nanoparticles in concrete specimens might increase the compressive strength. Kani et al.  studied 3COO)2OH at 450 °C and 300 °C at a 2 h soaking time. The manufactured ferric oxide nanoparticles demonstrated the buildup of fine ferrihydrite and hematite crystals with an almost 10–20 nm grain size. Ferric oxide nanoparticles increased the durability of composite pastes containing ferric oxide nanoparticles toward chloride and sulfate anion attacks. Mixes with 0.5–1.0% ferric oxide nanoparticles confirmed low values of total chloride and total sulfate contents. This was due to a finer and denser matrix with low porosity, which blocked the empty pores to the diffusion of chloride and sulfate anions, and therefore demonstrated increased values of bulk density and compressive strength.A study by Heikal et al.  examinedThus, overall, it was noted that the addition of ferric oxide nanoparticles to the concrete could improve its mechanical properties, such as its compressive strength. Further, the hardened concrete’s water absorption could also be improved with the inclusion of iron powder. Moreover, it was observed that the ferric oxide nanoparticles could increase the durability resistance of concrete against chloride, as well as sulfate anion attacks.Polycarboxylate, a nanomaterial, is an admixture in concrete. The construction of remarkable concrete structures have been benefited from the exceptional performance of present commercial polycarboxylate products, including the construction of the tallest skyscraper in the world—Burj Khalifa, Dubai, with an 820 m height. The development of higher-strength concrete, including a kind of polycarboxylate product and a retarder, permitted the structural concrete to be pumped up to an increased height of 650 m, and showed slump retention over 3 h at 50 °C for the concrete . The strMoreover, an increasing interest in the use of cellulose nanomaterials as fillers and reinforcement in concrete has been noted . Test rewww.zeon.co.jp, accessed on 5 October 2021) opened the world’s foremost mass-production facility for high-grade CNTs at its Tokuyama facility in Shunan City, Japan. This facility produces CNTs using the Super Growth (SG) method, and they have greater than 99% purity [As we can note, although nanomaterials offer superior properties to concrete, the majority are not used as much commercially, due to their limited availability, along with the increased price of the nanomaterials. However, global commercial interest in CNTs is reflected in their manufacturing capacity, which currently is more than several thousand tons/year . In 2015% purity . Table 32 and polycarboxylate. However, these nanomaterials are not very economical or as abundantly available as other supplementary cementitious material. However, if thorough research is carried out in this area, then there will be an opportunity to develop advanced, highly performing, durable, economical, and sustainable concrete. Nano-SiO2, carbon nanotubes, and titanium dioxide have good possibilities for use in nanoconcrete. Smart concrete and self-sensing concrete tend to find a suitable space in the construction sector. The application of specific nanostructured materials could improve the performance and the life cycle of concrete structures. Scientists are attempting to develop the manufacturing technology for producing nanomaterials at a commercial scale so that these materials will be easily accessible economically.So far, there have been no nanomaterials employed commercially in the construction sector, except for nano-SiOSpecific consideration must be given to the probability of penetration of water within the building matrices with the utilization of nanomaterials ,124,125.Another major challenge in using nanoparticles in the construction industries is the absence of their homogenous dispersion ,129. TheNanomaterial compatibility with building materials is another limitation in the application of nanomaterials ,132. SpeAnother drawback of the use of nanoparticles in the construction sector is the fact that at the time when nanomaterials are employed for enhancing the strength, the materials with higher strength also have a higher density, which results in greater structure weight .The high cost of nanomaterials is an extremely significant drawback in the use of nanomaterials in the construction sector ,137. ThiNumerous factors should be considered for developing nanomaterial-based concretes. First of all, the concrete and associated materials should be fabricated at a commercial scale. Although the expense of high-priced concrete structures turns out to be lower, it should have the capability of handling enormous materials in an ecofriendly and safer way. Second, advances need to be methodically established with field assessments to achieve the proper knowledge, as well as assurance in the concrete field. Finally, concrete structures are difficult to destroy and require greater energies or explosives to break up. Therefore, nanomaterial-based concrete fabrication must be compatible with the above-mentioned traditional practices.The advancement and progress of nanotechnology can upgrade the properties of building/construction materials, and thus assist sustainability ,150,151.Risk assessment examines the hazards to the health of humans and the environment of a sole substance at a specific point in its production time, service life, or discharge ,159,160.During the utilization of nanomaterials in the construction industry, exposure can lead to the inhalation of nanomaterials, or their absorption by straight contact with exposed skin. Consequences of nanomaterial exposure are not adequately realized, thus demanding studies to understand the interactions between nanomaterials and organic materials. Research works on the intake of many standard nanomaterials by mice generated understandings of the possible adversarial influences of nanomaterial exposure; however, generalization of the results was restricted by the experiment’s subjects ,171,172.3 must be considered [In relation to the most commonly used nanomaterials in the construction industry, it can be noted that their risks are different. Several nanomaterials are comprised in the venture that the Organization of Economic Cooperation and Development (OECD) has started to promote the complete characterization of nanomaterials already present in the market or soon-to-be commercialized . Steffennsidered . The afonsidered . Particunsidered . Inhalinnsidered . Furthernsidered  stated fWith the enhancement in the demands and applications of nanomaterials from formerly unrelated industries, the fabrication and exposure of nanomaterials has increased. Therefore, through transportation, disposal, washing, and erosion of the nanomaterial-enhanced products, these nanomaterials will find their way into ecosystems . The infSolid manufactured nanomaterial wastes from fabrication processes or the demolition and construction activities are transferred to legalized disposal sites. Before their dumping, these wastes most probably undergo a crushing process. Successive landfilling, land farming, and incineration might be the predominant methods for the ecological discharge of manufactured nanomaterials in the construction industry. The current available literature related to engineered nanomaterials incorporated in waste products; the possibility for the discharge of engineered nanomaterials from these products; and their probable fate in waste degradation, landfilling, incineration, and recycling was reviewed and assessed by Part et al. . ManufacOne of the significant problems with nanomaterials is the manner in which interactions occur involving materials that have been formerly regarded as harmless. Specially, though silver has been considered safe, studies have proposed that silver nanomaterial exposure in the embryonic stage of zebrafishes could stimulate irregularity in development or even death at levels greater than 0.190 nM . NonmariThus, a greater awareness of the novel products being established will also empower the building/construction industries to maximize the advantages that nanotechnology can contribute. With proper comprehension, there will be a development in the usage of products that were previously accessible but hardly specified; e.g., insulation that is four times as efficient as conventional materials, superior-performance concrete that lessens the requirements for steel reinforcement, or photocatalytic concretes that can decrease airborne contamination. It may also inspire the timely implementation of products that are prospective but not yet completely advanced; e.g., photovoltaic cells that can produce electricity from clear windows, or vanadium-based coatings that can eradicate the requirements for the cleaning of windows on high-rise buildings. Nanomaterials can contribute both risks and advantages. Currently, nanomaterials exist in a few commercial construction products; a couple of them are labeled, while others are not, and there are certainly further materials to develop. It is substantial that the building/construction industries identify sufficient information on the nanosized materials to take safe and smart decisions.The recycling of concrete is an important measure adopted for reducing the ecological effects of concrete structures at the end of their life cycle ,191,192.In a study carried out by Agarwal et al. , the teaWang et al.  fabricat2, basalt fiber, and composite addition of nano-SiO2, basalt fiber, could effectively enhance the interface structure and durability of recycled concrete.A work by Mukharjee et al.  addresseOn the other hand, the existing studies on nanomaterial-incorporated concrete are very limited, and therefore additional studies must be carried out to investigate the impact of nanomaterial-incorporated recycled concrete on its dynamic mechanical properties, and compare it with pristine standard concrete with respect to impact loading . BecauseDifferent bio-based nanomaterials are also recommended for the lowering the negative impact on the environment and on human health. In a study by Bang et al. , a new bAccording to the current review, the subsequent potential studies are suggested: (1) optimization of nanosilica-incorporated concrete, and the mathematical modelling of behaviour of concrete, need detailed investigation; (2) scientists should develop a high-performance, high-strength, and lightweight nanosilica-incorporated concrete; (3) it is essential to set up a basic approach of mixing design for this nanomaterial-incorporated concrete; (4) the hardened and fresh properties of nanosilica-incorporated concrete, needed for acoustical and thermal properties, should be evaluated; (5) properly examine the engineering properties such as shrinkage, creep, bond, etc. of nanosilica-incorporated concrete; (6) the optimal amount of superplasticizers for improved workability should be assessed; (7) the ultrasonication method demonstrated a noticeable outcome as regards the CNT dispersion, and hence, the concrete manufacturers should modify their facilities for accommodating the sonication technique. Consequently, the overall expenses must be assessed and compared with the attained advantages of employing the CNTs with ordinary Portland cement products; (8) studies on the mechanical characteristics and fundamental model of RC under dynamic actions is inadequate, and hence research in this area must be carried out; (9) proper assessment of the mechanical characteristics of recycled concrete in complex stress states and multiaxial conditions must be performed; (10) research should also be carried out on the development of the microstructure at the time of carbonation; and (11) studies on the durability and mechanical behavior of RC at higher temperatures must be performed, and a higher-temperature resistance modeling of RC must be put forward.For developing the commercial-scale production of advanced concrete materials, it is very important to have an effective technique for nanomaterial dispersion that will permit an appropriate and stable dispersion in concrete. Moreover, in the future, a significant challenge will be a decrease in the preparation expenses of the nanomaterials. It is always desired to make construction sector materials economical, energy-efficient, and sustainable. Some researchers are already carrying out studies for analyzing the negative impact of nanomaterials for specific applications ; howeverIn recent times, advanced nanotechnology has been meritoriously employed in various sectors for the comfort and welfare of humanity. Conversely, any groundbreaking unendorsed technology will come with some disadvantages. Presently, there are certain doubts regarding the conceivable unsafe influences of the nanomaterials on the surroundings. In general, the advanced nanomaterial-containing concrete for sustainable progress, being the century’s main priority, have prompted significant financial investment in the studies for defining novel avenues in the concrete field, suggesting the possibility of reducing ecological contaminations. A majority of the nanostructure-based products applied to date in the concrete sector have numerous advantages. There are several explanations for accepting the fact that the nanomaterial usage is rising. Sometimes, the nanomaterial production might need comparatively higher energy. Innovative concrete structures need structural components with superior mechanical properties, as well as higher durability. The best solution is the incorporation of nanostructured materials in concrete mixes, which could improve the mechanical properties. Nanomaterials such as nanosilica, nano-TiO2, CNTs, etc. have the capability for increasing the durability of buildings by improving mechanical and thermal properties, which could result in an indirect reduction in energy usage and total expenses in the concrete industry. The microstructures of various kinds of concrete is remarkably improved by the inclusion of nanomaterials, as the nanomaterials enhance the hydration process by generating more hydrated products. Incorporating various nanomaterials into the concrete mixes decreased the setting time as well as workability, which was due to the stronger reactivity of nanomaterials having a larger surface-to-volume ratio. Improvement in compressive strength could be observed with an improvement in the replacement ratio of nanomaterials. This was due to the improved hydration of a more compacted microstructure with the incorporation of finely dispersed nanomaterials. Moreover, it was noted that the nanomaterials could increase the concrete beam ductility by approximately 150%. With the incorporation of a nanomaterial such as CNT, the concrete compressive strength could be improved to 21%, and also it can result in a decrease in the early as well as long-term shrinking of concrete of 54.0% and 15.0%, respectively. Moreover, the CNT addition to concrete showed 17.0% to 18.0% reduced long-term creep as compared to the concrete with no CNTs. The inclusion of nano-titanium oxide in cement matrices could offer concrete frameworks with self-sensing as well as self-cleaning capabilities. Overall, it was noted that optimum concentrations of nanomaterial incorporation in the concrete could enhance its flexural, tensile, and compressive strength, along with the workability and water absorption. High-performance nanomaterial-incorporated concretes could positively impact the increase in the sustainability and durability of the constructions. The self-healing sustainable concrete frameworks obtained from different nanomaterials could restore the weakened constructions in an advanced manner at lesser expense, relative to that accomplished by epoxy-containing healing products, therefore attaining the ecological sustainability. The application of specific nanostructured materials could improve the performance of concrete, as well as its life cycle. The nanomaterial-incorporated concrete could permit the development of ultra-strength concrete frameworks having higher durability, and thereby decreasing the maintenance needs.It is extremely important to develop an advanced procedure to make sure the appropriate nanomaterial dispersion commercial-scale field applications. Effective dispersion of nanoparticles is key to achieving the full benefits of adding nanoparticles in cementitious system. So far, the nano-based technology is helping significantly for developing many technologies along with industrial sectors: including the construction sector. Because of the nonexistence of disposal guidelines, the amount of nanosized materials present in the surroundings is continuously increasing. Nano-based concrete structures were established to be ecofriendly with respect to greenhouse gas emissions, energy storage, and sustainable development. Thus, the current, as well as forthcoming, trends are to substitute the conventional ordinary Portland cement-based concretes with functional/smart nano-based concrete structures for sustainable developmentIt was noted the nanomaterials can play an important role in the development of construction materials, and thus proper understanding of these nanomaterials is extremely important. Along with the substantial advancement of nanomaterials in different applications, it should also be noted that the nanomaterials are still in their developing stages, and they definitely have many challenges and unsolved complications for their huge commercial prospects. The experimental test results of nano-reinforced cement specimens have confirmed that they could improve the durability and mechanical strength of the resultant concretes. This was also confirmed by different studies performed by scientists on the nano-reinforced cement ,205. TheMajor conclusions from this study are: (i) the construction sector has higher prospects of nanotechnology for solving certain complicated problems existing in this area; (ii) optimum addition of appropriate nanomaterial to the concrete can improve the mechanical properties such as tensile strength, compressive strength, flexural strength, durability, etc. of the concrete; (iii) freeze–thaw resistance and abrasion resistance of the concrete can also be improved with the addition of nanosilica to the concrete mix; (iv) nanomaterials can offer concrete structures with self-sensing and self-cleaning abilities; (v) however, the concentration of the nanomaterial present in the concrete should be in a very limited quantity; (v) the lack of information on nanomaterial toxicology topics and a tendency to disconnect from prevailing research and development is a significant blockade for its development; (vi) to suppress these type of restrictions, organized construction sector-strategic policies should be followed to benefit from the nanomaterials to attain a reasonable benefit in particular application extents and the product categories.2 globally, the addition of nanomaterials into the concrete mix reduces the essential size of concrete structures, leading to a lower emission of CO2 thereby making concrete an eco-friendly construction material. Thus, the environment pollution could remarkably decreased by applying high strong cement-based composites manufactured utilizing different nanostructured materials. Consequently, in the area of construction, the manufacture of nano-based materials is going to perform a substantial part toward sustainable development in the coming period. The application of nano-based concrete materials is beneficial with respect to enhanced engineering properties of cement materials, particularly for the production of sustainable as well as self-healing concretes.This study offered a complete and detailed analysis of improvement in concrete’s properties with the addition of nanomaterials, its risk evaluation, related health issues, and environmental implications of nanomaterial-based materials for the application in concrete sector. The review focused on the environmental impact and the future scope of the nano-based concrete materials. It was clearly noted that the nanostructured materials have higher capability in smart infrastructure applications with superior strength concrete frameworks. This study also featured a discussion on the prevailing issues and barriers to the commercialization of nano-based construction materials that harness the benefits of nanoparticles. It can be concluded that the application of nanomaterials in the construction sector can offer both risks and benefits. Presently, the nanomaterials are existing in some specific commercial items, and some of these are labeled, whereas some are not labeled. Hence, it is important that the construction sector must have satisfactory knowledge on the nanomaterials, and this will enable them to take safer selections. The main findings from this study are expected to raise awareness on the probable effect of construction wastes with nanomaterials in it and the importance of proper regulations regarding the final disposal of these construction wastes. As the production of concrete is accountable for higher than 5.0% of total emission of CO


This study aimed to determine and describe the prevalence of combination antibiotics dispensed in outpatients with health insurance in Syria. Data on all dispensed medicines between June 2018 and May 2019 for 81,314 adults were obtained, and medicines belonging to the J01 group of the World Health Organization (WHO) anatomical therapeutic classification (ATC) were included in the analysis. Prescriptions were stratified according to the number of antibiotics, age, and sex. Antibiotic utilization was expressed as the number of prescriptions per 1000 persons per year. Out of 59,404 prescriptions for antibiotics, 14.98% contained antibiotic combinations, distributed to 22.49% of the patients. The prevalence of dispensing antibiotic combinations was higher in female patients (23.00%), and the youngest  and oldest age groups . The antibiotics most commonly combined were co-amoxiclav, second- and third-generation cephalosporins, and macrolides. Over 60% of the combinations contained ceftriaxone alone or in combination with sulbactam. The present study shows an alarmingly widespread prescription of antibiotic combinations, posing a risk to global health by promoting resistance development. The rate of antimicrobial resistance (AMR) has grown substantially over the past two decades, posing a major threat to global health . There aIn Syria, a disastrous war has affected health care provision, and the burden of infections, morbidity, and mortality continues to grow . The groA recent study that described outpatient antibiotic utilization in Syria found evidence of the misuse of antibiotics. This included high rates of broad-spectrum antibiotic dispensing and a high proportion of the WHO Watch group of antibiotics . SubstanOut of 59,404 prescriptions for antibiotics, there were 8899 (14.98%) that contained more than one different antibiotic. The rate of total antibiotic prescribing was 730.55 and the combination prescription rate was 109.44 prescriptions per 1000 persons per year. The majority of prescriptions  contained two different antibiotics, while a lesser number contained three  or four  different agents. Out of 33,444 patients prescribed antibiotics, 7524 (22.49%) received a combination of more than one agent. The age and sex stratification of patients dispensed antibiotic combination therapy is presented in p < 0.001 (p < 0.001). Additionally, the sex-standardized rates of dispensed antibiotic combinations, expressed in packages of antibiotics per 1000 persons per year, were 119.56 in female vs. 92.73 in male beneficiaries.Based on the number of patients, the overall prevalence of antibiotic combination therapy was 22.49%. The dispensing of an antibiotic combination was most common in the youngest  and the oldest age groups ,  < 0.001 . As showThe top ten most common antibiotic combinations dispensed, accounting for 77.82% of the total dispensing of combination antibiotics, are presented in p < 0.001), with the highest age-standardized rates reported in the youngest age group . Combinations of penicillins with BLI and lincosamides were the most common in the 40–49 age group.When looking at individual agents, the top ten combinations, accounting for more than 50% of total combination antibiotic utilization, are presented in The present study has brought light to the high rate and worrying pattern of the dispensing of combinations of broad-spectrum antibiotics in outpatients with health insurance in Syria. H. pylori and tuberculosis [Almost a quarter (22.49%) of all patients receiving antibiotics in the outpatient setting received an antibiotic combination at least once during 12 months. Out of all the prescriptions for antibiotics, 14.98% contained more than one antibiotic. Combinations of antibiotics increase the selection of resistance through the exposure of bacteria to these drugs, leading to increasing costs and chances of side effects, resulting from drug interactions . The unnrculosis . Moderatrculosis . Unforturculosis . In Ethirculosis . Taking There are several possible reasons for why a physician may prescribe combinations of broad-spectrum antibiotics in the Syrian setting. A review article on the causes of antimicrobial resistance in LMIC countries identified a fear of bad treatment outcomes as one reason why physicians blindly prescribe multiple and broad-spectrum antimicrobials . AdequatThe prevalence of dispensing antibiotic combinations was higher in the youngest 18–30 years) and oldest (>70 years) age groups. Higher antibiotic use in the elderly is in line with the available evidence. In a systematic review where nineteen studies exploring age as a factor in antibiotic use were included, thirteen found a statistically significant association between older age and higher odds of antibiotic prescription . A study years anThe most commonly used combinations were those of penicillins, including beta-lactamase inhibitors and third-generation cephalosporins, followed by the combination of third-generation cephalosporins and macrolides, and two different cephalosporins. Combinations containing cephalosporins with macrolides and fluoroquinolones were more commonly used in patients over 60 years of age, while dual therapy with cephalosporins was more common in patients under 40 years of age. Combinations of beta-lactams with macrolides and fluoroquinolones are guideline-concordant therapies for moderate-to-severe community-acquired pneumonia. The problem of dual beta-lactam therapy was obvious when analyzing individual agents; the most commonly dispensed combination was amoxicillin, alone or in combination with clavulanic acid, together with ceftriaxone, or a ceftriaxone–sulbactam combination. The purpose of antibiotic combinations is to expand the spectrum of activity and enhance the effectiveness of the treatment. Antibiotic combinations should aim for a synergistic effect, while avoiding antagonistic and incompatible effects. The benefits of dual beta-lactam therapy remain unclear in the outpatient setting. Dual beta-lactam therapy is a strategy reserved for serious Gram-negative infections, as combinations of carbapenems were used in clinical trials as a rescue strategy for multidrug-resistant bacteria. Therefore, the dispensing of combinations of beta-lactams identified in the present study seems unwarranted. Worryingly, a large share of the identified antibiotic combinations (more than 60% of prescriptions) contained ceftriaxone, alone or in combination with sulbactam. Other studies have shown that ceftriaxone is the most common parenteral antibiotic in outpatient settings ,33,34. TThe present study had limitations that need to be mentioned. First, obtaining antibiotics without a prescription is common practice in Syria, but the data in the present study only included antibiotics prescribed by physicians. The results are representative of a population in Syria with health insurance, but are not generalizable to the whole population. The data did not include the drugs prescribed to treat diseases not included in the health insurance coverage in Syria . Standard measures of consumption, such as defined daily dose and defined daily dose per 1000 inhabitants per day, were not used in the analysis, making a direct comparison with other studies difficult. Finally, the lack of data on diagnosis did not allow for further analysis of the indications for which antibiotic combinations were dispensed. Still, this study contributes to our knowledge about antibiotic prescribing and misuse in LMICs. Considering the large sample size, the use of standardized methods for the drug classification and analysis, and the paucity of studies from this region of the world, the present study provides an important addition to the current knowledge on an often under-reported issue in antibiotic use.This retrospective cross-sectional study was based on the outpatient dispensing data from thirteen Syrian governates, excluding the Ar-Raqqa governorate, which is not under Syrian government control. The health insurance data from June 2018 to May 2019 containing outpatient medication dispensing were used. Data included the proprietary drug name, number of dispensed packages, pharmaceutical formulation and route of drug administration, prescription number, a unique number for each patient, date of dispensing, the name of the governorate, and patient’s age and sex. Unique prescription numbers allowed for analysis on the exact pattern of dispensed antibiotics during a single dispensing event. Data for 81,314 beneficiaries were present in the dataset. A detailed description of the study population is available in the previous publication [p-value less than 0.05 was considered significant. 4.3. Ethical ConsiderationsThe original dataset contained all dispensed medicines for the study population. Only medicines belonging to the ATC group J01  were included in the analysis. The 2020 version of the World Health Organization (WHO) ATC/DDD index was used to assign ATC codes to the respective international non-proprietary names (INN) . The comEach patient was given a unique identification number, but individual patients could not be identified. After the assessment, the ethics commission of the University of Bayreuth stated that their approval was not required for the analysis and reporting of the dispensing data in the present study.The present study gives evidence of a serious and previously unreported issue of using broad-spectrum antibiotics in combination in Syrian outpatients. This practice, far from appropriate drug use, poses a risk to local and global health by promoting AMR, and puts patients at an increased risk of side effects. Further studies on the exact reasons for the widespread prescribing of combination antibiotics by Syrian doctors are warranted. Nevertheless, the present study contributes to the knowledge on the role of antibiotic combination therapy in LMICs, a problem that must not be overlooked in future studies and during the development of antibiotic stewardship policies.


Therefore, it could be suitable for use in high pedestrian or traffic areas.Construction and Demolition Waste (CDW) is among the largest waste streams in the world. Therefore, within the Circular Economy concept, there is a growing interest in its reuse. The purpose of this work was to study the use of recycled aggregates (RAs) obtained by a specific separation method from CDW, replacing natural aggregates (NAs) in the manufacture of precast concrete elements, such as kerbstones and paver blocks. The physical and technological properties of precast products formulated with RAs were analysed in accordance with current regulations, comparing them with those of commercial products manufactured with NAs. The results indicated that partial or total substitution of NAs by RAs increased the water absorption and apparent porosity values of the precast elements while reducing the bulk density and compressive strength. However, all units manufactured with RAs showed breaking load values higher than the minimum required by EN 1338 and, in some cases, slightly higher average tensile strength values than the reference material. In addition, some of the compositions including RAs gave rise to pieces that, according to their flexural strength, were classified as class 1 and marked S in accordance with EN 1340. According to abrasion resistance, in most cases, the precast elements are classified as Class 4 and I (≤20 mm). Finally, precast concrete produced from RAs satisfies the tolerance requirements for classification as class 3 (≤1.5 kg m One of the strategic lines of the European Union policies aims to ensure the “Circular Economy” through the efficient use of raw materials and residues and the generation of clean energy. For that, policies on waste management must be directed in respect of the hierarchy of 4Rs established by the normative: reduction, reuse, recycle, and recovery .In this sense, one of the most generated wastes at the global level is Construction and Demolition Waste (CDW). It is important to note that from mid-2008 until early 2013, with the economic and financial crisis, the construction sector was gradually reducing the consumption of raw materials and, therefore, the generation of wastes. Then, since the end of 2014, the construction industry began its recovery [In the EU, the construction sector represents 9% of the Gross Domestic Product (GDP) , generatFor that reason, there is an increasing interest at the global level of reuse and recycling of these CDW. RAs from CDW have usually been focused on concrete road and pavement applications. Thus, it has been studied at the laboratory scale in pavements ; the man−2 and is composed of a mixture of clinker (97 wt.%) and natural gypsum (3 wt.%). Superplasticiser MasterCast 731, an additive-based polymer (polycarboxylate) supplied by BASF Company , was used. According to the technical data, this additive can reduce the water content while maintaining workability and improving the strength, durability, and shrinkage of the concrete. Finally, potable water was used in the present research for both casting and curing of the concrete. Furthermore, the recycled aggregates (RS and RG) were pre-saturated for 3 min through soaking in potable water to avoid the high WA values compared to natural aggregates (NS and NG) due to the presence of porous materials, such as bonded mortar, ceramic, clay, etc. [In the present study, 4 different aggregate types, natural sand (0–4 mm), natural gravel (4–12 mm), recycled sand (0–4 mm), and recycled gravel (4–12 mm) were used in the production of concrete specimens. Natural sand (NS) and gravel (NG) were supplied by the precast concrete company Montalbán y Rodríguez S.L., located in the region of Murcia (Spain). Recycled sand (RS) and gravel (RG) were provided by an integrated CDW treatment plant of the Murcia region. These types of RAs with physical and mechanical properties similar to those of NAs used in the present study are quite easy and cheap to obtain following the separation method reported in previous studies . This meay, etc. ,27,28. Aay, etc. ,29,30,31ay, etc. ,30,31. CConcrete mixtures were formed to determine the physical and mechanical properties of the concrete specimens using these four types of aggregate, cement, water, and superplasticiser. Concrete mixtures were prepared by substituting recycled  for natural aggregates. The aggregates , cement, superplasticiser, and water percentage by weight of the concrete mixture are presented in −1. Moreover, the chemical analysis was performed using the energy dispersive X-ray fluorescence (EDXRF) technique in a Bruker  S2 Ranger LE spectrometer fitted with a 50 W X-ray tube , Pd anode, XFlash silicon drift detector with <135 eV resolution for Mn-Kα and 100.000 cps and equipped with a Peltier cooling system (liquid nitrogen is not required), and primary filter tool changers with nine positions possible. Finally, the trace elements were measured by inductively coupled plasma mass spectrometry (ICP-MS) by using HP computer model HP4500 . The equipment was pre-calibrated with suitable standards.The mineralogical composition of the raw materials was carried out using the XRD (X-ray diffraction) technique in a Shimadzu  diffractometer model XRD 6000 with Cu-Kα radiation and operating at 1.2 kW (40 kV e 30 mA). The diffractograms were registered in the interval of 5–60° 2θ, with a step size of 1° minIn order to determine the physical properties of aggregates for concrete, bulk density (BD), specific gravity (SG), water absorption (WA), and Los Angeles (LA) abrasion loss were measured in accordance with the requirement established in the EN 12620 standard . BD and In addition to SG and WA, apparent porosity (AP) and compression strength (σ) were studied for concrete test specimens ,38,39. TFinally, WA and strength properties, tensile splitting (T), and bending (B) strengths were evaluated for concrete precast paving. The test for WA was conducted by following the same previously reported procedure and was expressed as the ratio of the mass of the absorbed water of an immersed specimen to the oven-dried mass. Tensile splitting strength tests with concrete block paving were conducted to measure the indirect T. They were conducted in accordance with the requirement of EN1338  and by u2 in RG and RS, respectively). In addition, their chemical composition includes minor components, such as aluminum (5.4–6.8 wt.% Al2O3), calcium (5.5–6.4 wt.% CaO), iron (1.9–2.3 wt.% Fe2O3), and magnesium (1.2–1.4 wt.% MgO), among others. In terms of mineralogy, the predominant crystalline phase in the recycled aggregates is quartz (SiO2), with calcite (CaCO3) and portlandite (Ca(OH)2) as secondary phases. Silicon oxide is also the major component of natural aggregates (90.6 wt.% SiO2 in NS and 63.2 wt.% SiO2 in NG), together with other minor elements, such as aluminum (3.8 wt.% Al2O3), magnesium (1.3 wt.% MgO), calcium (1.5 wt.% CaO), and iron (1.2 wt.% Fe2O3) in NS or calcium (10.5 wt.% CaO), aluminum (4.8 wt.% Al2O3), iron (2.9 wt.% wt.% Fe2O3), sodium (1.5 wt.% Na2O), and magnesium (1.2 wt.% MgO) in NG. As expected, quartz is also the principal crystalline phase found in natural aggregates, along with smaller amounts of calcite and feldspar in the case of NS. On the other hand, the chemical composition of Portland cement type I is mainly composed of CaO (59.9 wt.%) and SiO2 (21.5 wt.%), with Al2O3 (5.9 wt.%), Fe2O3 (2.8 wt.%), and MgO (2.2 wt.%) as minor components.The chemical and mineralogical composition of the raw materials used in this study has been fully discussed in a previous paper . Briefly−3, whereas the RS and RG are slightly lower, ~1450 kg m−3, by considering the experimental uncertainties, regardless of the type of CDW (∼1400 kg m−3). Furthermore, the results of BD obtained under compacted conditions of natural constituents (NS and NG) and recycled aggregates (RS and RG) were similar and around 1600 kg m−3. Similarly, the specific gravity (SG) was slightly higher in the natural aggregates  in comparison to recycled aggregates  because the density of natural constituents is higher than that of recycled aggregates [−3  of natural and recycled aggregates are collected in gregates ,16,25. Mgregates , which sates [−3 . On the Finally, the mechanical properties of coarse aggregates (NG and RG) were studied according to Los Angeles abrasion (LA) test . The EHEThe addition of recycled aggregates, either RS or RG, to replace natural aggregates results in a slight increase in water absorption values . Even soTest specimens containing RAs show compressive strength values in the range 28–37 MPa, while the reference material reached an average value of 37 MPa . TherefoOnce the RAs’ incorporation had been studied in concrete with satisfactory results, both the kerb units and the paver blocks containing RAs were prepared on a laboratory scale. Regarding apparent porosity, −1 stated in the EN-1338 [−1  the loss of mass achieved the maximum value of 1.3 kg m−2. The control prefabricated units were also tested, exhibiting similar values to the precast elements with recycled aggregates. Unlike the previous properties, the repeatability of the freeze–thaw resistance values increases considerably in the concrete elements with substitution of NAs for RAs, with the increase being greater as the percentage of replacement increases.The progression of the accumulated scaled material of precast concrete samples prepared with 100 wt.% of RAs over 28 freeze–thaw cycles is illustrated in nnexes E ,42. FurtIn this manuscript, the use of RAs, fine (RS) and coarse (RG), obtained by a specific separation method from CDW as substitution of NAs, sand (NS) and gravel (NG), in the manufacture of kerbstone and paving blocks was analysed.−3) and RAs (1450 kg m−3) in loose condition and 1600 kg m−3 in compacted conditions for both NAs and RAs samples. Specific gravity (SG) was slightly higher in the NAs  in comparison to RAs . The mechanical properties of coarse aggregates (NG and RG) show a Los Angeles abrasion test value of 25 and 33%, respectively, within the limit given by current regulation.In relation to the physical properties, bulk density was quite similar for NAs  by RAs (RS and RG) were carried out. As a general conclusion, the addition of RAs increases the water absorption and apparent porosity, reducing the real density and compressive strength. Specifically, samples with a substitution of NAs by RAs at 25 wt.%  show a similar compressive strength  with a reference material (37 ± 3 MPa).−3, while a substitution of 25 wt.% of RAs (RG and RS) presented an average tensile strength of 3.7 MPa, slightly higher than a reference material (3.6 MPa). Additionally, replacements up to 50 wt.% of RS (RS50) or RG (RG50) or 25 wt.% of RS + RG (RSRG25) fulfil the requirements for pavers established in the EN-1338 standard. Moreover, bending strength of concrete kerbs manufactures samples was evaluated. The samples with replacements of 25 wt.% of NAs by RAs (RSRG25) are clearly higher than 3.5 MPa, being classified according to the EN 1340 as class 1 and S mark. According to abrasion resistance, most elements manufactured are classified as Class 4 and I (≤20 mm of abrasion wear) while reference RG100 and RSRG100 belong to Class 3 and H (≤23 mm). Finally, precast concrete elements produced with RAs satisfy the tolerance requirements for classification as class 3, for which the loss of individual mass must be lower than 1.5 kg m−2. Therefore, these precast elements can be used in pedestrian areas or areas with little traffic.Finally, the kerbs and paver blocks were manufactured at laboratory scale in order to evaluate the breaking load and tensile splitting strength. All specimens manufactured with RAs showed values of breaking load higher than the minimum given by EN-1338, 250 NmmRegarding the repeatability of the values, in general, the absolute error increased, and the repeatability decreased in the units manufactured with RAs, with the exception of the freeze–thaw resistance where a considerable increase in repeatability is observed as the percentage of substitution of NAs by RAs increases.


Salmonella Typhimurium (ASST) and antibiotic-resistant S. Typhimurium (ARST) during the broth microdilution assay. The antimicrobial activity in association with antibiotic stability was measured by using antibiotic susceptibility, time-delayed inoculation, time-extended incubation, and inoculum effect assays. The loss of the antimicrobial activity of cephalothin against ASST exposed to 1 MIC was observed for the 10 h delayed inoculation. The antimicrobial activities of tetracycline and ciprofloxacin against ASST and ARST exposed to ½ MIC were significantly decreased after the 10 h delayed inoculation. All antibiotics used in this study, except for ciprofloxacin, showed the considerable losses of antimicrobial activities against ASST and ARST after 40 h of incubation at 37 °C when compared to the 20 h of incubation during AST. Compared to the standard inoculum level (6 log CFU/mL), the MIC0.1 values of bactericidal antibiotics, ciprofloxacin and tobramycin against ASST were increased by more than 4-fold at the high inoculum level of 9 log CFU/mL. This would provide practical information for better understanding the clinical efficacy of the currently used antibiotics by considering the antibiotic stability during incubation time at different inoculum levels.This study was designed to evaluate the stability of chloramphenicol, erythromycin, tetracycline, cephalothin, ciprofloxacin, and tobramycin against antibiotic-sensitive  Antibiotics are mainly classified based on their target sites, including the inhibition of cell wall synthesis, protein synthesis, nucleic acid synthesis, membrane function, and metabolic pathway ,2. TheseSalmonella Typhimurium under the conditions of time-delayed inoculation, time-extended incubation, and different inoculum levels.The accurate determination of the antibiotic susceptibility of bacteria remains a key factor for optimizing the antibiotic treatment regimen in association with pharmacokinetic (PK) and pharmacodynamic (PD) properties . HoweverThe antibiotic susceptibility testing against ASST and ARST was conducted to evaluate the antibiotic stability in media at the 0 h and 10 h delayed inoculation . CephaloThe antimicrobial activities of chloramphenicol and erythromycin against ARST exposed to ½ MIC were significantly decreased at the 0 h inoculation after 20 h of incubation at 37 °C compared to 1 MIC a,b, whilThe antibiotic susceptibilities against ASST and ARST were evaluated after 20 h and 40 h of incubation as shown in the dose–response curves . All ant0.1 values of chloramphenicol, erythromycin, tetracycline, cephalothin, ciprofloxacin, and tobramycin were compared to evaluate the inoculum effect . The highest fold change in the MIC0.1 of ciprofloxacin was observed at the inoculum of 9 log CFU/mL of ASST, showing a more than 4-fold increase, followed by tobramycin (>3-fold)  a. The MIg CFU/mL b.The antimicrobial activity is directly associated with the antibiotic stability during the AST. For instance, the incubation and inoculation conditions can affect the degradation of antibiotics during the broth microdilution assay, ultimately resulting in inaccurate AST results. Therefore, the AST results might not provide sufficient information on the antibiotic stability over the incubation period . CephaloThe dose–response curves for chloramphenicol, erythromycin, tetracycline, cephalothin, and tobramycin showed a significant decrease in antimicrobial activity against both ASST and ARST after 40 h of incubation when compared to 20 h . The resThe antimicrobial activity varies with the classes of antibiotics . Tetracy0.1 values of all antibiotics tested in this study were significantly increased as the inoculum levels of ASST and ARST increased, known as inoculum effect [5 to 106 CFU/mL) but antibiotic resistance at high inoculum levels [0.1 value  and antibiotic-resistant S. Typhimurium CCARM 8009 (ARST) were obtained from American Type Culture Collection  and Culture Collection of Antibiotic Resistant Microbes , respectively. The strains were sub-cultured at 37 °C for 20 h in trypticase soy broth (TSB) . The activated cells were collected at the late exponential phase by centrifugation at 5000× g for 10 min at 4 °C. The harvested cells were washed twice with phosphate-buffered saline  and adjusted to 108 CFU/mL.Strains of antibiotic-sensitive 6 CFU/mL of ASST and ARST. The plates were incubated for 20 h at 37 °C to determine the minimum inhibitory concentration (MIC) of each antibiotic.The susceptibility of ASST and ARST to chloramphenicol, erythromycin, tetracycline, cephalothin, ciprofloxacin, and tobramycin  was eval6 CFU/mL in 0 h incubated and 10 h delay incubated 96-well microtiter plates containing ½ MIC and 1 MIC of antibiotics. The growth of each test strain was measured after 20 h of incubation at 600 nm using a microplate reader .The antibiotic stability was evaluated in bacterial culture media by using a delay-time assay . ASST or5 CFU/mL. After 20 h and 40 h of incubation at 37 °C, the dose–response curves of ASST and ARST were generated to evaluate the changes in antibiotic susceptibility.The degradation of the antibiotics used in this study was evaluated by broth microdilution assay  with a s2 to 8.2 × 109 CFU/mL and inoculated in each well of 96-well microtiter plates containing antibiotics serially (1:2) diluted from 1024 to 0 µg/mL. MIC0.1 values were determined at the lowest concentrations of antibiotics at which the optical density (OD) at 600 nm reached 0.1 after 20 h of incubation at 37 °C. The fold change was determined by the ratio of the MIC0.1 of each antibiotic at different inoculum levels to the standard inoculum level (106 CFU/mL).The inoculum effect on antibiotic activity was evaluated by comparing MICs determined at different inoculum levels of ASST and ARST . The tes®  was used to determine the MIC0.1 values of the antibiotics.The experiments were carried out in duplicate for three replicates. All data were analyzed by general linear model (GLM) and Fisher’s least significant difference (LSD) to determine significant differences at 5%, 1%, and 0.1% significance levels. The nonlinear curve fitting function of Microcal OriginThis study describes the effects of incubation time and inoculum level on antibiotic stability. AST is the first step to evaluate the antimicrobial potential and then determine the effective antibiotic treatment of bacterial infection. The most significant findings in this study were that the stabilities of chloramphenicol, erythromycin, tetracycline, cephalothin, ciprofloxacin, and tobramycin during the AST were highly influenced by incubation time, which might be a key factor in determining antimicrobial sustainability and antibiotic concentration; in addition, the antibiotic susceptibility of ASST and ARST was decreased at a high inoculum level when compared to standard inoculum, showing the noticeable inoculum effect of ciprofloxacin against ASST and cephalothin against ARST. Antibiotic stability is considered as an important factor for successful chemotherapeutic use. Thus, the AST might not provide sufficient information about the efficacy of antibiotics in association with the antibiotic stability under the incubation and inoculation conditions. The misinterpretation of the results obtained from the AST ultimately results in the underestimation or overestimation of antibiotic efficacy in clinical practice. Therefore, the current antibiotic susceptibility assays need to be re-evaluated by taking all test conditions (incubation time and inoculation level) into account in providing clinical guidelines and recommendations for chemotherapy and accurately predicting pharmacokinetics and pharmacodynamics in vivo.


Although C-ros oncogene 1 (ROS1) targeted therapies have demonstrated remarkable efficacy in ROS1-rearranged non-small cell lung cancer (NSCLC), patients inevitably develop resistance to ROS1-tyrosine kinase inhibitors (TKIs). Commonly acquired resistance mechanisms include a second mutation of the ROS1 kinase domain and activation of bypass signaling pathways. However, MMNG HOS Transforming gene (MET) amplification has not been reported as a novel mechanism of ROS1-TKIs resistance.in situ hybridization of the primary cancer showed no MET amplification, suggesting that MET amplification may be associated with an acquired resistance to ROS1-TKIs.We report a case of a 62-year-old man diagnosed with ROS1-rearranged metastatic lung adenocarcinoma, who received first-line treatment with crizotinib for 19 months. During the course of disease, the primary lung tumor was under control while the brain metastasis progressed despite the treatment with lorlatinib. The biopsy and genetic tests of the metastatic brain tumor showed a high level of MET amplification (32 copies). However, fluorescence This case suggested that MET amplification could be explored as a potential mechanism for developing ROS1-TKIs resistance. Combination treatment with highly potent and selective MET-TKIs warrants further investigations. C-ros oncogene 1 (ROS1) has been identified as an oncogenic driver in 1–2% of non-small cell lung cancer (NSCLC) . HoweverIn this study, we reported a case wherein a high level of MMNG HOS Transforming gene (MET) amplification was found at the time of progression, as a potential mechanism for ROS1-TKIs resistance in NSCLC.in situ hybridization (FISH) . Pulmonary biopsy revealed lung adenocarcinoma stage IV (T1cN2M1c). Immunohistochemistry (IHC) results of the tumor tissue were positive for ROS1 and PD-L1 (> 90%) but negative for anaplastic lymphoma kinase (ALK) Figure 1via next-generation sequencing . Unfortunately, the patient succumbed to the intracranial hypertension and cerebral hernia before the NGS report, which showed a high level of MET amplification (32 copies). FISH demonstrated a cluster of MET signals congruent with the NGS result  scan of the chest showed the primary lesion still under control. The patient then received lorlatinib 75mg once daily, but his symptoms were not relieved. Instead, his dizziness and the muscular weakness in both lower extremities worsened. New symptoms, such as headache, convulsions, sluggishness, and unresponsiveness developed. A repeated brain-MRI showed rapid brain tumor progression, severe brain edema, and cerebral midline deviation Figure 2MET amplification activates a bypass signaling pathway that is responsible for resistance to EGFR and ALK TKIs , 7. Howevia different mechanisms: MET secondary mutation and MET amplification. Further studies are needed to confirm these finding.Crizotinib, a multitargeted ALK/ROS1/MET inhibitor, was the first TKI approved by the FDA for the treatment of ROS1-rearranged advanced NSCLC in 2016 . It inhi50 for MET amplification (0.58 µM) compared to that for ROS1 (31nM for SDC4–ROS1 fusion)  , 18. Thetely 4nM , which wtely 4nM , which iIn previous studies, patients harboring acquired MET amplifications after disease progression benefited from combination therapy that targeted both the primary driver and MET gene . A phaseIn summary, this case suggested that MET amplification may be an important mechanism for acquired resistance to ROS1-TKIs. The combination of crizotinib and a more potent MET inhibitor should be investigated post-crizotinib progression in ROS1-rearranged NSCLC patients who harbored acquired MET amplification.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.in situ hybridization. MY: patient care and case presentation. YZ: conceptualization, writing-review and editing. All authors contributed to the article and approved the submitted version.JY: collected the clinical data and wrote/edited the final manuscript. PZ: analyzed and interpreted the histological examination, immunohistochemistry stains, and fluorescence The authors acknowledge financial supports from the 1·3·5 project for disciplines of excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University (Grant No. 2019HXFH062), and from the National Natural Science Foundation of China (Grant No. 81402561).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.