Antimicrobial resistance (AMR) is a threat to public health, impacting both human and animal health as well as the economy. This study sought to describe antibiotic prescription practices and use in the Kintampo North Municipal Veterinary Clinic in Ghana using routinely collected data. Of the 513 animals presented for care between 2013 and 2019, the most common animals were dogs (71.9%), goats (13.1%), and sheep (11.1%). Antibiotics were prescribed for 273/513 (53.2%) of the animals. Tetracycline was the most commonly prescribed class of antibiotics, (99.6%). Of the 273 animals that received antibiotics, the route of administration was not documented in 68.9%, and antibiotic doses were missing in the treatment records in 37.7%. Details of the antibiotic regimen and the medical conditions diagnosed were often not recorded (52.8%). This study recommends appropriate documentation to enable continuous audit of antibiotic prescription practice and to improve quality of use. There is also the need for a national survey on antibiotic prescribtion and use in animal health to support policy implementation and decision making in One-Health in Ghana. Antimicrobial resistance (AMR) is an increasing threat to public health and advances in the fight against infectious diseases ,2. AntibWhile trends in antibiotic consumption in humans are increasingly being tracked globally, antibiotic consumption in livestock and the veterinary service has received comparatively little attention . There iThe Ministry of Health (MOH), Ghana, has developed Standard Treatment Guidelines to aid the appropriate use of medicines, including antibiotics . These gTo holistically address the challenge of AMR, WHO adopted the Global Action Plan (GAP-AMR) in 2015 based on the concept of “one health” to implement strategies through relevant sectors and stakeholders. It is expected that the use of antimicrobial agents in humans, plants, and animal health would be optimized in the ‘one health’ approach through specific interventions to promote the responsible use of antimicrobials in humans, veterinary, and aquaculture as well as in the environment and industry . In lineThis study explored (a) the number and type of animals receiving veterinary care, (b) proportion of animals receiving antibiotics by type of animal, (c) the prescription practices , and (d) the type of antibiotics used at Kintampo Municipal Veterinary Clinic, Ghana, from 2013 to 2019.This was a descriptive study using routinely collected secondary data from the treatment records at the Kintampo Municipal Veterinary Clinic.The livestock sector contributes to about eight percent 8%) of Ghana’s Gross Domestic Product (GDP) . Veterin% of GhanThe Veterinary Council of Ghana is responsible for supervising veterinary doctors. There is a national information management system that collates monthly and quarterly reports from the district officers through the regional directorate. Every district has a District Veterinary Officer and several veterinary paraprofessionals. Currently, there is no national electronic database, so that all the reports are sent in as hard copies . The govThe Kintampo North Municipality is located within the forest-savannah in the middle belt of Ghana . The humThe Kintampo Municipal Veterinary Clinic was selected for this study because it is the only clinic providing veterinary services in the study area. Though the clinic is situated in the municipality, its catchment area includes more than 100 rural communities. The size of these rural communities range from 40 compounds to approximately 1500 compounds . As of 2There is a standard treatment register at the clinic where data on the management of the animals is recorded. It includes the type of animal, breed, diagnosis, dosage of medicine (if prescribed), and route of administration. Quarterly reports are sent to the regional directorate as part of a monitoring and evaluation system.All animals treated in the Kintampo Municipal Veterinary Clinic from 2013 to 2019 were included in the study.Data were extracted from the treatment register of the Kintampo Municipal Veterinary Clinic, including details, such as the type of animal , date of treatment, condition for which the animal was treated, and use, type, dosage, and route of administration of antibiotics if they were prescribed. The principal investigator extracted the data, which were then double entered by two senior data entry clerks. However, due to missing data, treatment records from 2016 and 2017 were not included in the study.Data were entered into an Excel spreadsheet and imported into Stata 14 for analysis. The number and percentage of various types of animals treated across 2013 to 2015 and 2018 to 2019 were described. The number and proportion of animals treated with antibiotics were calculated across the study years. Similarly, the number, dosage, and route of antibiotics administered were calculated.In total, 513 animals were presented for treatment during the study years , . The mosIn 2013, 57% of animals received antibiotics compared to 36.9% in 2019. There was a decrease (55.0% to 36.9%) in the use of antibiotics between 2018 and 2019 .Of 513 animals, more than half received antibiotics . For the most common animals  antibiotic prescriptions ranged from 51% to 63%, as shown in The tetracycline class of antibiotics (272 out of 273) was almost exclusively used, while penicillin was used for only one animal. Of the 273 animals receiving antibiotics, the route of administration was not documented in the majority  and the details of antibiotic dosage were missing in the treatment records for one in three animals . Of the 85 (31.1%) animals in whom the route of administration was mentioned, injection was the most common , followed by dermal application  and oral . About 271 (52.8%) of the disease conditions were not specified out of which 145 (53.5%) were still treated with antibiotics .Antibiotics were prescribed to more than half of the animals that presented for care; virtually all were tetracycline. Considerable gaps in documentation, including failure to record diagnosis, dosage of antibiotic, and route of administration, were observed.Our findings on the considerable use of tetracycline to treat animals are similar to studies conducted in Rwanda and Ghana among animal farmers and veterinary care providers, where oxy-tetracycline was commonly used ,21. ThisThe WHO recently classified veterinary antibiotics according to their risk to compromise antibiotic treatment for humans ,27,28,29Incompleteness in the recording of the diagnosis, antibiotic dosage, and route of administration was observed. This finding is similar to inadequate documentation practices found in human  and animThere are some important limitations to our study. First, we could not fully capture antibiotic prescription trends across the entire study period as data were missing for two years. Second, data on the medical conditions among the animals receiving antibiotics were inadequate as they were either missing or lacked sufficient detail. Hence, it was not possible to gauge to what extent antibiotic prescriptions were justified. Finally, we cannot generalize the findings to other settings as we only collected data from one veterinary clinic. Notwithstanding, our findings highlight the need for a broader national survey to further assess antibiotic prescription practices in the veterinary service as an important step for decision-making by key stakeholders, such as the Ghana National AMR platform.Antibiotics, specifically tetracycline, were commonly used for the treatment of animals in one veterinary clinic in Ghana within the context of poor documentation of antibiotic prescription and use practices. There is a need for a national survey to further assess antibiotic prescription and use practices to support decision-making by stakeholders in the fight against antimicrobial resistance in Ghana and other low- and middle-income countries.


The presence of autoantibodies in IgG4-related disease (IgG4-RD) can lead to confusion and we present a case to highlight the diagnostic difficulty in this condition.A 63-year-old Indian female presented with progressive ptosis and swelling of the left eyelid for 2 months. She was referred to the stroke clinic where she was found to have left ptosis with associated swelling. An MRI of the orbit revealed an enlarged left lacrimal gland and mucosal thickening in paranasal sinuses. Her ESR was 20, CRP 2, 15% peripheral eosinophils and IgG 17.55 g/L (6-16). A referral was made to rheumatology due to an abnormal immunological profile: cANCA +, MPO ANCA positive 32 IU/ml (0-3.5) and a strongly positive anti-Ro antibody >600 U/ml (0-10). Differential diagnosis considered: ANCA associated vasculitis (AAV), Primary Sjögren’s syndrome (SS), and IgG4-related orbital disease. She was assessed by the ENT surgeon and there was no sinusitis or evidence of vasculitis. Chest X-ray and CT scan of chest were normal.A left lacrimal gland biopsy revealed reactive lymphoid hyperplasia with numerous plasma cells and eosinophils. Immunohistochemistry revealed over 50% of plasma cells to be IgG4-positive (approximately 100/HPF) suggestive of IgG4-RD. There was no evidence of granuloma formation or malignancy. Serum IgG4 was raised 6.82 g/l (<1.3). A review by ophthalmology revealed no objective evidence of dry eyes. She was treated as IgG4-RD and demonstrated a marked improvement following treatment with oral steroids and azathioprine.IgG4-RD is an immune-mediated systemic fibro inflammatory disease characterised by tumefactive lesions with abundant IgG4-positive plasma cells infiltrating into multiple organs. Isolated IgG4-related ophthalmic disease is present in 23% of patients with IgG4-RD, in whom the lacrimal gland is the most commonly involved structure, followed by orbital fat and extraocular muscles. IgG4-related ophthalmic disease is rare and we need to exclude commoner causes of orbital inflammation  or malignancy.The diagnosis of IgG4-RD is often challenging. It is well recognised that small vessel vasculitis can increase the number of IgG4-positive plasma cells in tissue biopsies. Additionally, literature reveals biopsy-proven IgG4-RD can have ANCA positivity with and without concomitant presence of ANCA-associated vasculitis and there are case reports of patients who fulfil criteria for both Sjogren’s syndrome and IgG4-RD. As such, diagnosis requires careful correlation of clinical, radiologic and histological features due to the overlapping features in differential diagnoses.


The summary PK exposure measures were normalised to the minimum inhibitory concentration (MIC), an in vitro measure of the pharmacodynamic (PD) potency of the drug. The three PK-PD indices  have been used extensively since the 1980s. While these MIC-based summary PK-PD metrics have undoubtedly facilitated the development of new antibiotics and the clinical application of both new and old antibiotics, it is increasingly recognised that they have a number of substantial limitations. In this article we use a historical perspective to review the origins of the three traditional PK-PD indices before exploring in detail their limitations and the implications arising from those limitations. Finally, in the interests of improving antibiotic development and dosing in patients, we consider a model-based approach of linking the full time-course of antibiotic concentrations with that of the antibacterial response. Such an approach enables incorporation of other factors that can influence treatment outcome in patients and has the potential to drive model-informed precision dosing of antibiotics into the future.Within a few years after the first successful clinical use of penicillin, investigations were conducted in animal infection models to explore a range of factors that were considered likely to influence the antibacterial response to the drug. Those studies identified that the response was influenced by not only the total daily dose but also the interval between individual doses across the day, and whether penicillin was administered in an intermittent or continuous manner. Later, as more antibiotics were discovered and developed, antimicrobial pharmacologists began to measure antibiotic concentrations in biological fluids. This enabled the linking of antibacterial response at a single time point in an animal or  Understanding that relationship is critical in the nonclinical and clinical development of a new antibiotic because it guides the dosage regimens to be evaluated in clinical trials and subsequently the regimens included in the product information at the time of regulatory approval of the antibiotic product  era . Pleasin product . In the  product .In this review we briefly look back at key events in the birth and development of the discipline of antibiotic PK-PD. In particular, we focus on a key product of that development, three so-called PK-PD indices, that have been the most common way to link antibiotic PK exposure and antibacterial PD response in studies conducted since the late 1980s. Next, we consider in detail major limitations of those PK-PD indices, and a number of important implications associated with the limitations. Finally, in the interests of moving forward and fostering the ongoing evolution of the discipline, we consider alternative approaches that offer very substantial promise of enhancing the scientific approach to the development and rational clinical use of antibiotics.in vivo exposure to the antibiotic arising from different dosing regimens. Based on his experimental observations, he stated that “the primary determinant of therapeutic activity is the time for which the drug remains at effective concentrations at the focus of infection” and, remarkably, suggested that continuous infusion of penicillin was likely to be the most effective way to administer the drug to patients , the ratio of the area under the plasma concentration-time curve to the MIC , and the percentage of time for which the plasma concentration exceeds the MIC . Those extensive landmark studies identified that the antibacterial activity of aminoglycosides was best predicted by AUC/MIC, while for β-lactams the antibacterial activity was correlated with %T>MIC  have been used for many years. The uses include: informing of many important steps in the development of new antibiotics, especially the choice of dosage regimens to be examined in clinical studies  with a measure of the PD “potency” of the antibiotic as provided by the MIC determined in vitro. An appreciation of the limitations of these PK-PD indices requires an understanding of the way in which the indices and the associated target values for various magnitudes of bacterial kill are determined.Fundamentally, each of the PK-PD indices is an attempt to link a summary PK measure of exposure  (5–108 colony forming units (CFU)] of the microorganism under investigation; at least three, and preferably more, bacterial strains should be studied for each antibiotic-species pair  fraction of the drug. This information is used to convert each PK-PD measure to the corresponding index referenced to the microbiologically active free drug i.e. fCmax/MIC, fAUC/MIC and %fT>MIC as shown in via the sigmoidal maximum effect (Emax) function, and the index with the highest statistical correlation to the antibacterial response is considered to be the most predictive PK-PD index. As an example, Pseudomonas aeruginosa ATCC 27853 between the log10 CFU/thigh at 24 h and fAUC/MIC of colistin; of the three PK-PD indices, fAUC/MIC was the most predictive of antibacterial activity as assessed by CFU counts at 24 h  estimate probabilities of target attainment for various clinical dosage regimens of the antibiotic  . The neuies pair . After 1ily dose . After 2 at 24 h . The mos at 24 h , relativtibiotic .There are several important limitations related to the traditional PK-PD indices, a number of which occur because only one assessment time point, usually at 24 h, is used to quantify the impact of treatment on the total bacterial population . The firNot surprising in view of the above considerations, it has become increasingly evident that the choice of the most predictive traditional PK-PD index and the magnitude of that index required for a certain level of bacterial kill or resistance suppression may be influenced by a number of factors. These include the characteristics of an isolate, for example whether the isolate is hypermutable  or hetein silico a murine dose-fractionation study of meropenem to examine the sensitivity of the “most predictive” PK-PD index to experimental design , drug susceptibility and different PK profiles    and bothnly used . This apin vitro infection model (HFIM)  over 10 days, the response to each regimen was vastly inferior for the hypermutable strain. This was the case even though the MIC values were the same for both strains, and the intermittent infusion and continuous infusion regimens achieved identical exposures  against each strain  provided a generally applicable link between PK exposure and PD response.Whether or not a bacterial strain is hypermutable can also affect the applicability of traditional PK-PD indices, as demonstrated by studies in a hollow-fibre l (HFIM) . That sth strain . In addih strain . Heteror testing . Howevercolistin . In othe profile . The resmax, AUC) that ignore the shape of the exposure profile; and, 3) failure to recognise and capture information on bacterial characteristics such as hypermutability and heteroresistance. Importantly, the three traditional PK-PD indices do not incorporate factors other than antibacterial effect that may have an important influence on the clinical outcome in a treated patient. Such factors include the immune status, presence of comorbid conditions and severity of overall illness of the patient. Clearly, the limitations discussed above arise even when antibiotics are used in monotherapy regimens, and an additional substantial limitation is that the three indices cannot be used to optimise the exposure profile of each antibiotic in combination therapy  PD response in the nonclinical infection model being assessed at a single, relatively early, time point; 2) use of summary PK metrics  converge to conceal covert resistance, i.e., heteroresistance  subpopulations. These models can enable translation to the clinic by being interfaced with a population PK model for the relevant patient group to predict the influence of established covariates of PK exposure  on bacterial killing and development of resistance for antibiotic monotherapies and combination treatments, and also suggest dosing regimens for clinical evaluation (via model-informed precision dosing (MIPD)  . Such ang (MIPD) . Mechanig (MIPD) . Such ang (MIPD) . This wog (MIPD) .The three traditional MIC-based PK-PD indices have brought us a long way over the last several decades and will continue to find application for some time. However, it is important to move beyond those empirical metrics and more fully explore scientifically robust approaches of linking the time-course of exposure to an antibiotic with the time-course of its antibacterial effect, while also having the ability to integrate other factors that can influence treatment outcome in an infected patient. Looking to the future, a wonderful opportunity and challenge for the field of antibiotic PK-PD will be to continue to develop, refine and evaluate the translational and clinical application of mechanism-based models and other approaches aimed at streamlining the development of new antibiotics and optimizing the dosing of new and old antibiotics in individual patients. Success in this endeavor would be expected to make a wonderful contribution to efforts aimed at improving survival of individual patients, while addressing the ever-present threat of resistance and preserving the activity and clinical utility of precious antibiotics into the future.


We estimated the fraction of antibiotic prescribing in the United Statesattributable to gonorrhea. Gonorrhea contributes to an outsized proportion ofantibiotic prescriptions in young adults, males, and in the southern and westernUnited States. A gonococcal vaccine could substantially reduce antibioticprescribing in these populations. Antibiotic resistance poses a growing threat to human health . AntibioGonorrhea is the second most prevalent reportable illness in the United States, withnearly 600 000 cases reported in 2018 ,and is Neisseria meningitidis vaccine and aclinical trial of meningococcal group B vaccine (Bexsero) for gonorrhea is ongoing[There are currently no licensed gonococcal vaccines, although modest protection has beendemonstrated from the MeNZB  ongoing, 8. An eAtlasPlus portal [We extracted annual cases of gonorrhea and chlamydia by state, sex, and age group in the United Statesfrom 2015 through 2018, the most recent years available, from the CDC’sWe extracted outpatient antibiotic prescriptions from the Truven MarketScandatabase  over theNext, we estimated the number and proportion of azithromycin prescriptions,ceftriaxone prescriptions, and overall antibiotic prescriptions in the UnitedStates that were attributable to gonorrhea in 2015–2018. Treatment forgonorrhea is normally administered under the supervision of a provider upondiagnosis, so these antibiotics are not recorded in the outpatient prescriptionsdata. We therefore added 1 dose of azithromycin and 1 dose of ceftriaxone foreach reported gonorrhea infection. Similarly, we added 1 dose of azithromycinfor each reported case of chlamydia. This is a conservative choice, sincechlamydia may be treated by a single supervised dose of azithromycin(recommended) or a 7-day course of doxycycline. Full details on theseadjustments are given in the For the years 2015–2018, we calculated the percentage and total number ofazithromycin prescriptions, ceftriaxone prescriptions, and total antibioticprescriptions per 1000 people that were attributable to gonorrhea. For 2018,when gonorrhea incidence was at its highest level in over a decade, wecalculated the same statistics stratified by age, sex, and US Department ofHealth and Human Services (HHS) region . VaccineThere were 1.79 reported cases of gonorrhea per 1000 individuals in the United Statesin 2018. These accounted for 1.5% of all azithromycin prescriptions, 82.9% of allceftriaxone prescriptions, and 0.53% of all antibiotic prescriptions of any typegiven in 2018 . The incThe updated ceftriaxone monotherapy treatment guidelines for gonorrhea willeffectively halve the total number of antibiotic prescriptions due to gonorrhea.Gonorrhea-associated azithromycin prescribing will decline effectively to zero,while gonorrhea-associated ceftriaxone prescribing should remain roughly unchanged,barring major changes in the relative prevalence of gonorrhea and other illnessestreatable by ceftriaxone.u = 0.5), consistent withadolescent human papillomavirus (HPV) vaccine uptake in the United States [e = 0.5) and a high vaccine efficacy of 90%(e = 0.9). In 2018, a gonococcal vaccine with 50% uptake and50% efficacy would have reduced gonorrhea-related antibiotic prescribing by anestimated 25%, so that the overall percentage of antibiotic prescriptions due togonorrhea would have been 0.40%. Among 20- to 24-year-olds, such a vaccine wouldhave reduced the proportion of antibiotic prescriptions due to gonorrhea from 2.38%to 1.78%. For a vaccine with 50% uptake and 90% efficacy, gonorrhea-relatedprescribing would decline by an estimated 45% and thus gonorrhea would haveaccounted for 0.29% of all antibiotic prescriptions and 1.31% of antibioticprescriptions among 20- to 24-year-olds. Had monotherapy been in place in 2018, thebaseline proportion of antibiotic prescriptions due to gonorrhea ; if avaccine also reduces gonococcal transmission, further reductions in prescribing maybe expected. We have focused on gonorrhea incidence in the United States, but weanticipate that a gonococcal vaccine would similarly lead to substantial reductionsin antibiotic prescribing worldwide.Clinical InfectiousDiseases online. Consisting of data provided by the authors to benefitthe reader, the posted materials are not copyedited and are the sole responsibilityof the authors, so questions or comments should be addressed to the correspondingauthor.Supplementary materials are available at ciab276_suppl_Supplementary_MaterialClick here for additional data file.


Fiber-reinforced polymer (FRP) composites have been used in various industries, thus a large amount of FRP wastes have been generated due to the out-of-service of FRP products. Recycling FRP wastes into coarse aggregates to replace natural coarse aggregates (NCA) to form the recycled FRP aggregate concrete (RFAC) is a potential approach to dispose of huge quantities of FRP wastes with low environmental impact. In this paper, waste glass FRP (GFRP) bars were cut into particles of 12 sizes to enable the grading of recycled FRP aggregate (RFA) as similar as possible to that of NAC. The influence of different RFA volume replacement ratios  on the compressive performance of RFAC was investigated based on uniaxial compression tests of 15 standard cylinders. The results showed that the failure mode of RFAC was different from that of NAC. As the RFA replacement ratio increased, the compressive strength and elastic modulus of the RFAC gradually decreased, but its post-peak brittleness was significantly mitigated compared to NAC. The Poisson’s ratio of RFAC increased with the increase in the RGFA replacement ratio at the elastic stage and was smaller than that of NCA concrete. Both the existing stress–strain models developed for NAC and recycled aggregate concrete (RAC) were found not fit for the RFAC. Thus, a new stress–strain model that was applicable to RFAC was developed by modifying the classical existing model, and a good agreement between the model predictions and test data was reached. Being equipped with advantages such as lightweight, high strength and corrosion resistance, fiber-reinforced polymer (FRP) has gained extensive application in various industries, including construction, shipbuilding, wind power industry and aerospace industry ,3,4,5,6.In the past, landfill or incineration was the usual treatment of FRP waste. However, it is expected that the landfill cost will increase significantly in the future  and thatAt present, mechanically recycling wastes GFRP and applying them into the concrete mixture as one of the ingredients is an eco-friendly and energy-saving approach ,16,17. IFor recycling FRP into granular to replace the natural coarse aggregates (NCA) in concrete , the mecBesides, there is some research related to making FRP rebar into “needles” to replace NCA in concrete. Yazdanbakhsh et al.  found a The above literature review indicates that the research on recycled FRP aggregates concrete (RFAC) is limited and that no relevant stress–strain model can be found in the open literature at present. Therefore, in this paper, waste GFRP rebar was recycled by cutting into particles to replace the NCA in concrete. Aggregate grading was considered when manually recycling GFRP bars. The effect of different GFRP volume replacement ratios on the performance of concrete was investigated, including failure mode, compressive strength, modulus of elasticity, lateral dilation and stress–strain response. The test results showed that the compressive strength and modulus of elasticity decreased with increasing RFA replacement ratio and that the failure mode of RFAC was different from that of natural aggregate concrete (NAC). Comparisons between test results and existing constitutive laws indicated that the stress–strain models originally proposed for NAC and recycled aggregate concrete  cannot be used directly for RFAC. To better understand the behavior of RFAC under compression, a new and accurate stress–strain model is developed.The waste GFRP bars were manually cut into short cylindrical (the diameter kept the same as the respective GFRP bar) particles with the length determined by considering aggregate grading, which was then used to replace NCA with different volume percentages to form the so-called RFAC. To investigate the effect of volumetric replacement ratio of GFRP aggregates on the axial compressive behavior of RFAC, this paper designed 15 standard cylinder specimens (150 mm in diameter and 300 mm in height) with the recycled GFRP aggregates (RGFA) replacement ratio of 0%, 30%, 50%, 70% and 100% considered, as summarized in The materials used in the test were ordinary Portland cement (OPC) 42.5R, water, fine aggregates (river sand), NCAs (crushed stone) and RGFAs. The RGFAs used in the test were obtained by manually cutting the GFRP rebars with diamond saw blades, which included four kinds of diameters, i.e., 6 mm, 12 mm, 14 mm and 22 mm. The GFRP straight bars (no sand-coating) were provided by a local supplier . The mechanical properties of the GFRP bars are summarized in The uniaxial compression test was carried out using a 3000KN MTS, and a displacement control loading mode (0.3 mm/min) was adopted. Four longitudinal linear variable differential transformers (LVDTs) were fixed on the body of each specimen to monitor the longitudinal displacements, as shown in As shown in Based on the above comparisons and discussions, three reasons can be found for the strength reduction of RFAC. First, the surface of the RGFA mentioned above was smoother, and the shape was more regular than that of the NCAs. As a result, the interfacial transition zone (ITZ) between the RGFA and the cement paste was much weaker, resulting in a significant decline in its strength. Other researchers also made similar remarks ,26. SecoThe stress–strain relationship of concrete under compression is an important basis to quantitatively evaluate the mechanical properties. For both NCA concrete ,50,51,52β. For the model proposed by Chu et al. [β, while in the model of Yi et al. [t, elastic modulus In this section, four representative stress–strain models of NCA concrete were selected to compare with the test curves (only one test curve in each group was used), the expressions of which are summarized in u et al. , the stri et al. , the cur’s model  is divid’s model  adopts aa and b by considering the recycled aggregate replacement ratio r. In addition, Xiao et al. [In terms of RAC, four existing stress–strain models were also selected for comparison, and the specific expressions are summarized in o et al.  adjustedg et al.  was modig et al.  by consi EU Code , Belen e EU Code  introducBased on the analytical constitutive law proposed by Guo and Zhang , which wr was introduced, as expressed in Equation (5). A comparison between the predictions of Equation (3) and the experimentally measured values is shown in In the new stress–strain model, the peak strain ognestad , as exprstandard , where aa and b in Equations (1) and (2) are specific parameters for a given strength level of the concrete. The coefficient a is the shape parameter that controls the ascent stage of the curve, which is equal to the initial elastic modulus divided by the cutline modulus at the peak point  . The coeIn this paper, waste GFRP bars were cut into 12 kinds of granular shapes (with aggregate gradation considered) to replace NCA to form the so-called RFAC. The main test variable of standard RFAC cylinders was the volume replacement ratios of RGFA, i.e., 0%, 30%, 50%, 70% and 100%. Uniaxial compressive tests were conducted to evaluate the effect of RGFA replacement ratios on the mechanical properties of RFAC, including compressive strength, peak strain, modulus of elasticity and stress–strain response. Based on the existing constitutive law, a new stress–strain model was modified and developed for RFAC. The following conclusions can be drawn:The failure mode of RFAC was different from that of NCA concrete. Unlike NCA concrete failed by an obvious main diagonal crack, the cracks of RFAC were found to be distributed without an obvious main diagonal crack. This phenomenon was more significant as the RGFA replacement ratio increased.The compressive strength Under the same axial stress, RFAC tended to expand more easily , especially in the post-peak softening stage. The Poisson’s ratio of RFAC at the elastic stage was slightly smaller than that of NCA concrete and tended to increase with the increase of the RGFA replacement ratio, but the overall change range was small, ranging from 0.14 to 0.20.The shape of the stress–strain curve of RFAC was different from that of NCA concrete, especially in the post-peak softening range. This can be due to the following changes of RFAC, including the weaker interfacial bond between GFRP aggregates and cement matrix, larger lateral expansion under the same axial stress and different cracking pattern.Comparisons between the test results and existing stress–strain models developed for NCA concrete as well as RAC indicated that the existing models are not suitable for predicting the stress–strain relationship of RFAC. Thus, based on the existing classical models, by considering the RGFA replacement ratio, a set of new models were proposed to predict the modulus of elasticity, peak strain and stress–strain model of RFAC, and good agreements were found between the models’ predictions and test results.The conclusions drawn from the current study are based on the test results, discussions and theoretical modeling presented above. Notably, due to the fact that only limited ranges of parameter variation were considered in this work and that no other existing stress–strain curves can be found in the open literature, further studies are needed to substantiate and further improve the findings presented in the current work. Future research work can be carried out in improving the interfacial properties between FRP aggregate and mortar, and developing methods to enhance the compressive behavior of RFAC can also be an interesting area.


The optimization of the amount of cement in concrete can be achieved either by partially replacing it by additions or by reducing the binder content. The present work aims at optimizing the properties of concrete used in the production of reinforced concrete poles for electrical distribution lines, combining the maximization of compactness with the partial replacement of cement by fly ash, natural pozzolans, and electric furnace slags. Natural aggregates were also partially replaced by recycled ones in mixtures with fly ash. Two types of concrete were studied: a fresh molded one with a dry consistency and a formwork molded one with a plastic consistency. The following properties were characterized: mechanical properties  and durability properties . The service life of structures was estimated, taking the deterioration of reinforcement induced by concrete carbonation or chloride attack into account. Results revealed that mixtures with fly ash exhibit higher mechanical performance and mixtures with fly ash or pozzolans reveal much higher durability results than the full Portland cement-based mixtures.The sustainability of the construction sector demands the reduction of CO The same association proposes measures that will lead to a reduction in CO2 emissions of the production process of up to 3.5%, in 2030, and 8%, in 2050. The proposed strategy aims at the use of zero-carbon materials, such as natural, waste materials and by-products from other industries, such as pozzolans, fly ash, granulated slag, silica fume, and others, resulting in a good example of industrial symbiosis [In recent years, there has been growing concern about environmental sustainability and global warming causes and effects. The construction sector has a very important role in reducing the greenhouse effect and promoting sustainability. It is estimated that, in 2018, cement production reached 3.99 billion tons worldwide [ymbiosis .Optimizing concrete’s eco-efficiency should not harm its mechanical and durability properties. Previous studies prove that it is possible to produce concrete with low cement content and good mechanical performance ,6. ConcrThe most commonly used additions in cement replacement are silica fume, fly ash, ground granulated blast furnace slag, metakaolin, and limestone filler, amongst other industrial by-products. Most studies focus on the addition of fly ash  dIn the last decade, research on the properties of concrete with coarse recycled concrete aggregates, as substitutes for coarse natural aggregates, has increased substantially ,27,28,29The problems associated with the durability of the reinforced concrete structures, as well as concrete poles, are related with the corrosion risk of the rebars due to permanent exposure to very aggressive environments, such as chloride ions and carbonation. Chloride induced corrosion is one of the most frequent causes of concrete deterioration ,37, comp3. For the optimization study, the quantity of binder was established at 350 kg/m3, in order to guarantee the workability and cohesion of the fresh mixtures [In this sense, this work is part of a research project that aims to improve the formulation, eco-efficiency, performance and durability of a precast reinforced concrete used to produce poles for the electric distribution lines. Its main goal is to develop eco-efficient concrete solutions, combining high compactness with partial cement replacement by natural additions and by waste by-products from other industries and with the inclusion of recycled concrete aggregates. This study intended to develop the following points: (i) assess the influence of the maximum increase in compactness without loss of the required workability; (ii) analyze the effect of different additions  as cement substitutes; (iii) evaluate the combination between the considered additions and high compactness in the mechanical and durability properties of concrete; (iv) study the correlation between those properties, namely between different durability tests ; (v) predict the service life for different exposures to chloride and carbonation ingression. Currently, the production of concrete poles is divided into two types: one with dry consistency for fresh molded concrete (BT series); and other with plastic consistency concrete (MT series), for formwork molded concrete. The mixtures considered as a reference are those currently produced in the industry, with cement content between 360 and 400 kg/mmixtures . Based o3, were characterized: 3.08; 2.30; 2.30 and 3.83. The chemical composition of the powders is presented in 3: 2.63 for sands, 2.66 for gravels and 2.30 for RA. The RA were characterized with absorption of 4%. Tap water from public supply and two types of admixtures were used: HE200P (HE), a water reducer and hardening accelerator for molded cohesive concrete with dry consistency, with density of 1.17 kg/dm3, favoring a better dispersion for the BT mixtures; Sky526 (SKY), an ether-polycarboxylate based superplasticizer with a density of 1.06 kg/dm3, to increase plasticity and reduce the water content for the MT mixtures.The optimized concrete mixtures with low cement content were formulated and compared with reference fully cement-based mixtures, in order to evaluate the mechanical performance and durability of the optimized concretes. In these mixtures, the following powder materials were selected: CEM II-A/L 42.5R (C); F-type fly ash (FA); Cape Verde natural pozzolans (Poz) and ground electric furnace slag (Slag). The corresponding density values, in kg/dm3 into account. The corresponding amount of cement was between 200 to 250 kg/m3, depending on the selected additions and on the target strength of circa 50 MPa, at 56 days. The resulting proportions of additions varied from 29% to 43% for those mixtures. Admixtures’ dosages were adjusted to achieve the target consistency of each mixture, whose content in relation to the cement weight varied between 2.9% and 4.5% in BT and between 0.7% and 1.1% in MT series. The concrete was mixed with pre-wetting of recycled aggregates, with around 30% of the total water, waiting about 5 min, preventing the admixture from being partially absorbed with water. Then, the remaining solid constituents were placed and mixed, then the remaining water with the diluted admixture was added, mixing until obtaining the pre-defined homogeneity and consistency. The molds were filled and compacted with the vibrating table, being the compacting energy low in MT mixtures and high in BT mixtures.Regarding concrete mixtures, two types of consistency were considered and divided in two series, BT-dry consistency and MT-plastic consistency. The mixtures were formulated based on the method proposed by Lourenço et al.  and deveConcrete formulations are presented in To measure the consistency, the slump test was performed, according to EN 12350-2 , or the 3 and the flexural strength was assessed following EN 12390-5 [3. The Young’s modulus test was performed at 28 days following the LNEC E 397 [3. 3, according to the LNEC E 393 [ 12390-5 , in two EC E 397 , using tEC E 393 . The depEC E 393 , using tEC E 393 , using tEC E 393 , at 56 aEC E 393 .The results of average strengths of tensile splitting test, at 28 and 90 days, for BT and MT mixtures, are shown in The graph shown in According to EC2 , the teneff, the compressive strength of RAC is generally lower than the compressive strength of the same mixtures only with natural aggregates. However, this effect depends on the design and strength of the concrete matrix and also on the quality and strength of the concrete that origins the RA. In this study, considering that the concrete used to prepare the RA has 20% lower strength that the designed concrete and that is mostly uncompact waste concrete, a strength lost was expected. The standard deviations of all mixtures are reduced, although with some exceptions, being, however, within the limits considered by EC 2 [The compressive strength values with the error bars for the BT and MT mixtures, at 28 and 90 days, are shown in  by EC 2 .By analyzing the graphs, it is possible to observe that, in both series, in mixtures without pozzolanic additions, the hardening curve is more pronounced at early ages and tends to stabilize earlier. On the contrary, the curves of mixtures with pozzolanic additions are less pronounced in early ages, developing more in later ages, being a clear consequence of the pozzolanic effect of the fly ash and pozzolans.The measured average values of the Young’s modulus at 28 days are shown in E is a factor that depends on the type of natural aggregates used in the mixtures, which is 9500 for siliceous aggregates; fcm is the average compressive strength; αRA is the substitution rate of normal by recycled concrete aggregates and is given by the ratio between the quantity of recycled sand and gravel and the total quantity of aggregates in the concrete.The analysis of the graph allows to conclude that the values obtained in the Young’s modulus test are always higher than the predicted. Mixtures with the addition of pozzolans stand out, with values 26% and 17% higher than those predicted, in the BT200-Poz and MT250-Poz mixtures, respectively.The characterization of all mixtures had already been carried out in mortar matrices , which ia (mg/mm2) with the square root of time, for BT and MT mixtures, after 28 days curing. By analyzing the results, performed on three consecutive days, it can be concluded that the capillary water absorption occurs with more intensity in the first hours and tends to stabilize over time, presenting a nonlinear evolution. In both series, the decrease of the powder content combined with the increase of compactness and the partial replacement of cement by additions proved to be advantageous in decreasing water absorption over time. However, this fact is more prominent in MT series, since the values of optimized mixtures in BT series remain similar to the reference. In the latter, the addition of fly ash (50% of replacement rate) and the inclusion of 20% of recycled aggregates does not change the capillary absorption of concrete. Comparing the two series, it is noticeable that the amount of cement influences this parameter, proved by the lower values of the BTref (with cement content of 400 kg/m3), in relation to MTref (with 400 kg/m3). However, the optimized mixtures with fly ash show that the increase in compactness and the replacement of cement by this addition also has a great influence on the reduction of capillarity, as the concrete matrix becomes more compact and less permeable. In BT series, despite of the 50% of cement replacement, the capillary absorption is similar to reference. However, in MT mixtures, the optimized matrix with high compactness, and about 30% of cement replacement by fly ash, promotes a significant reduction in capillarity, of at least 35%.a. Browne [a coefficient: above 0.2 mg/mm2 × min1/2 is “low quality”; between 0.1 and 0.2 mg/mm2 × min1/2 is “medium quality” and below 0.1 mg/mm2 × min1/2 is “high quality”. According to this classification, all mixtures are considered to be of “high quality”, regarding the water absorption through capillarity. In addition, due to pozzolanic effect of the optimized mixtures, there is great potential to improve the performance for longer ages, beyond 28 days.In MT mixtures, the partial cement replacement by fly ash and 20% of recycled concrete aggregates, mixture MT250-FA-RA, leads to down to 44% less water absorption, and the mixture with natural aggregates (MT250-FA) presents equally reduced values. . Browne  proposedSimilar to what occurs with the absorption of water by capillarity, the addition of fly ash shows significant reductions of water penetration under pressure. The optimized mixture with higher compactness and addition of fly ash, MT250-FA, presents values down to 65% of less penetration depth when compared to the reference. The substitution of 20% natural aggregates through recycled concrete aggregates, combined with the previous matrix, make its compact matrix noteworthy, showing a 58% reduction in relation to the reference. The mixture with the addition of pozzolans, MT250-Poz, reveals the lowest water penetration result, very close to the value of the mixture with fly ash addition. This analysis reinforces that the higher compactness, and matrix refinement due to fly ash addition, of the optimized mixtures, it is quite important to reduced concrete permeability. In addition, the pozzolanic effect will promote even better results at more advanced ages, where lower penetration results are potentially expected.The phenomenon of concrete carbonation is mainly associated with the penetration, by diffusion, of carbon dioxide. The decrease in pH is visible through the reaction with phenolphthalein sprayed in concrete, in which the carbonated area is colorless .di), measured in mm, of the BT and MT series, with the square root of time. The analysis of carbonation depth, Cdepth, of the studied mixtures proved to evaluate that it varies with the square root of time, as expected, with a general trend to be linear. The amount of cement highly influences this parameter, and that effect is more evident in BT mixtures, whose reference contains a higher amount of cement than in MT mixture. However, BT250-slag mixture proves that the slags are the most beneficial additions in this series, showing a slower initial evolution and only 46% of increased carbonation depth in relation to the reference. On the contrary, also in BT series, the increased compactness and the partial replacement of cement by fly ash (BT200-FA and BT200-FA-RA) is not able to avoid the increase of the carbonation depth, up to 122%, when compared to the reference. Through these mixtures, it can also be concluded that the inclusion of 20% of recycled aggregates does not increase carbonation, on the contrary, it is slightly lower. Previously to this study, in mortar matrices, pozzolans additions did not reveal promising results in preventing carbonation [bonation . In concIn the MT series, the difference between the optimized mixtures and the reference is not so evident, since the cement replacement is lower (30%), presenting a similar evolution of the carbonation depth for the first testing ages. This evolution is less pronounced after 56 days, with the exception of the MT250-slag mixture, which shows a more pronounced increase of the carbonation depth, presenting values up to 69% above reference. This effect was not noticed for younger testing ages on the preliminary study of mortar matrices, since the carbonation evolved linearly with square root of time up to 90 days. Unlike the BT series, the optimized mixtures with fly ash of MT series, MT250-FA, present values closer to the reference, showing an increase of up to 31%, at the longer tested age. The inclusion of recycled aggregates, once again, did not harm the performance of the concrete at this parameter, presenting similar evolution with lower values to the homonymous mixture with natural aggregates. Despite additional absorption, water is considered in concrete with RA, the probable absorption during setting time may reduce the effective water of the mixtures with RA, which seems to result on a positive effect on carbonation reduction.The penetration depth of chlorides into the specimen is visible through the silver colour area, which corresponds to the silver nitrate precipitation, as is shown in 0) by non-steady state migration test at 56 and 90 days. In this test, the lower the D0 coefficient, the higher the resistance to chloride migration, the durability performance also being higher. This test highlights the benefit of pozzolanic additions (both fly ash and pozzolans), bringing the pozzolanic refinement to the porous network of the matrix, combined with increased compactness, in reducing the chloride migration. The results shown in The addition of natural pozzolans stands out positively by presenting very low D values, down to 64% and 81%, below the references for mixtures BT200-Poz and MT250-Poz, respectively, at 90 days. Due to its high content of alumina, when pozzolans are combined with cement, it promotes a reduction of the porous structure of the matrix with time, being beneficial to durability related with to corrosion risk, induced by chloride penetration, and to strength performance. 0 coefficient maintain its value from 56 to 90 days. Contrarily, the MT250-FA-RA mixture reduces the diffusion coefficient. Apparently, the higher cement content and lower replacement rate, in comparison to BT mixtures, is the probable reason for that difference.The results reveal similarly low values for the BT200-FA and MT250-FA mixtures, down to 80% and 77%, respectively, at 90 days, when compared to the references. This effect is already scientifically known. However, the inclusion of recycled aggregates affects the increase in the diffusion coefficient, when compared with similar mixtures with only natural aggregates, although it presents values 51% and 70% below the references for BT200-FA-RA and MT250-FA-RA, respectively. It is important to note that, in the BT200-FA-RA mixture, the D0, as used in [ used in .According to this classification, and by analyzing the plotted graph, it is possible to note that only the references, both BT and MT, present a “moderate” resistance of concrete to chloride penetration, although the BTref mixture achieves a classification of “high” resistance, at 90 days. Mixtures optimized with additions and increased compactness reveal very promising classification results. The mixtures with the addition of pozzolans (more evident in MT250-Poz) stand out for mostly obtaining the classification of “extremely high” resistance to chloride penetration. Mixtures with fly ash also stand out for the same reason, although they are mostly classified as “very high” resistance. The replacement of natural aggregates by recycled concrete aggregates does not greatly harm the mixtures, since, after 90 days, they are maintained, at least, with the classification of “very high” resistance.Through the analysis of the graphs, in both series, it is possible to conclude that the slag addition does not lead to positive results in this test, presenting similar values to the references with plain cement binder. The reference mixtures and those with slag addition have no significant variations of electrical resistivity with age. The opposite is found in mixtures with pozzolanic additions, which present results that increase with the testing age. Mixtures with fly ash addition stand out for having higher values, almost 20 times higher than the references, for both BT200-FA and MT250-FA mixtures, measured at 450 days. The pozzolan addition shows resistivity values nearly 6 and 16 times higher than the references, for BT250-Poz and MT250-Poz, respectively, also at 450 days. Despite fly ash and natural pozzolan both being pozzolanic additions, their influence on resistivity is different with time regarding the evolution and the optimal replacement rate. The electrical resistivity evolves faster with age, up to 56 days, for mixtures with pozzolan addition and develops a smoother evolution after that. Contrarily, the mixtures with fly ash addition present smooth evolution at younger ages, but after 120 days the increase in rate with age tends to be faster, probably due to higher pozzolanic reactivity at greater ages. However, at 300 days, mixtures with both additions tend to stabilize, although mixtures with fly ash stabilize more smoothly. In the MT series, the MT250-Poz mixture is very close to MT250-FA, showing closer values of resistivity evolution over time; a lower cement replacement by pozzolans, in comparison to the BT series, seems to suggest a possible optimal for moderate replacement rates (circa 30%). Contrarily, in the BT series, the higher cement replacement of fly ash in the mixture BT200-FA, 50%, suggest that the resistivity increase is more effective for higher fly ash content, mainly for longer ages. In fact, in a previous study carried out in mortar matrixes , it was The followed standard  refers t0, of the mixtures and the surface resistivity, ρ, of the corresponding matrixes, which is very reliable, and was proved by the high R2 values of the power function.Environmental exposure XC (corrosion induced by carbonation)C65 (kg × year/m5), of each developed concrete was calculated using Equation (3) and the carbonation depth, Cdi. These values were measured after the concrete was exposed for a certain time to a highly concentrated carbon dioxide environment, Cacel, 90 × 10−3 kg/m3.i is the time of exposure in years, and Xi has the same meaning as Cdi (carbonation depth). C65, at 56, 90, and 120 days to minimize the errors related with the measurement of the carbonation depth.The determination of carbonation resistance, Ric, and the propagation of corrosion, tp. The minimum propagation period, tp, depends of several factors, such as the exposure class.The deterioration of reinforced concrete due to steel corrosion can be divided into two periods: the initiation, tp, according to LNEC E-465 [g, is equal to 50 years, and considering that the electrical poles can be associated to the reliability class (RC1), where the safety factor of the service life is equal to 2.0 [ic, can be determined using Equation (4)  .tic = γmin,dur, is determined using Equation (5), considering the RC65 already calculated for each concrete and t is equal to the design period of initiation, tic X=2 0 is a factor related with test conditions and is equal to 3, k1 is a factor related with relative humidity, k2 is a factor related with concrete cure conditions and is also 1, n is a factor related with the influence of wetting/drying cycles over time, and t0 is the reference period and is 1 year. The meanings of the symbols are: kg, when the cover used is already predefined. For this purpose, X must be equal to the cover predefined, and tic is the unknown variable that should be calculated using the Equation (5). Usually, the randomness of the factors that affect the service life happens during the initiation period, so after the determination of tic, the service life, tg, is calculated adding to this value the propagation period, tp, presented in The Equation (5) can also be used to predict the service life, tThe service life was computed for different exposure classes considering covers equal to 15, 20, and 30 mm, see It is clear that higher cement content provides a better performance regarding durability related with carbonation, since the two reference concrete mixtures had the highest service life. The results of Environmental exposure XS (chloride-induced corrosion)p, also depends of several factors, and, according to LNEC E-465 [2/s), is determined for each developed concrete using Equation (6) and using the experimentally determined values of non-steady-state migration coefficients, D0 , the design period of initiation, tic, can be determined using Equation (4) and is 100 years for XS1 and XS3, and 20 years for exposure class XS2.0 is the time of the experimental tests to evaluate D0; t is the exposure time in days; ξ is a parameter related with the concentration of chlorides in the binding paste; X is the cover. The minimum concrete cover required to protect the steel reinforcement against corrosion induced by chlorides, cmin,dur, is presented g, for 20 and 30 mm is presented in For environments exposed to chlorides, the minimum propagation period, tEC E-465 , those vEC E-465 . The chlents, D0 . Using EIt is highly improbable that electric poles will be placed in tidal splash or spray zones or will be permanently submerged, but the results show that poles manufactured with these concretes should not be used in such zones. In environments with air-based sea salts, the reference concretes have a performance that is clearly worse than concretes with additions, which is reflected in the values of minimum cover, as well as in the service life expected. Among the concretes with additions, the behavior is relatively similar, showing that the pozzolanic additions can replace the cement dosage in the context of protection against corrosion induced by chlorides. It is also noted that, in this case, the incorporation of recycled aggregates slightly increases the minimum cover and decreases the expected service life. To assure a service life of 50 years for poles manufactured using these eco-efficient concretes, for both types of consistency, the cover requires ranges between 15 and 31 mm, which are the values usually used in the production of this type of structures.Tensile splitting strength: (i) unlike the BT series, the addition of fly ash increases this strength by 31% in plastic concrete with natural aggregates, MT250-FA, and by 22% with recycled concrete aggregates, MT250-FA-RA, compared to the reference; (ii) the addition of recycled aggregates reduces this strength by 9% when compared to the same mixture with natural aggregates; (iii) the test results and the prediction values of EC2 are very similar, with a difference of about 10%.Flexural strength: (i) although cement reductions are high (from 30 to 50%) in optimized mixtures, those with the addition of fly ash and slag show an increase of up to 27% in MT250-slag mixtures, compared to the respective reference, at 90 days; (ii) the inclusion of recycled concrete aggregates have practically no influence on this parameter; (iii) the prediction of EC2 has very similar values to those obtained in the tests, since this strength is directly related to the tensile splitting.Compressive strength: (i) mixtures with additions tend to increase from 28 to 90 days, due to the pozzolanic effect and, despite the cement reduction, it increases up to 26% with fly ash and natural aggregates (MT250-FA), and up to 14% with fly ash and natural and recycled aggregates (MT250-FA-RA), at 90 days, in comparison to the reference; (ii) the hardening curve of EC2 prediction has an R (rapid) evolution at early ages in concretes without pozzolanic additions, contrary to the curve of mixtures with pozzolanic additions, which has an S (slow) beginning, but a more pronounced evolution at later ages.Young’s modulus: (i) adding supplementary cementitious materials  to the concrete increases this parameter, mainly in the case of pozzolans addition, that lead to increases of 11% and 13%, for BT200-Poz and MT250-Poz, respectively, comparing to the references; (ii) as expected, the inclusion of recycled concrete aggregates reduces this parameter, due to their lower stiffness; (iii) the test results are always higher than those predicted with the codes, with increases of up to 26% for the mixture with the addition of pozzolans, BT250-Poz.Capillary water absorption and water penetration under pressure: (i) in dry BT concrete, the high content of fly ash addition (50% of cement replacement rate) combined with high compactness is beneficial, since it presents the same capillarity as the reference; (ii) concrete with plastic consistency–MT, where 30% of the cement was replaced by fly ash addition, shows even more positive results, absorbing 44% less capillary water than the reference; (iii) the inclusion of recycled concrete aggregates is also beneficial, since it presents similar or lower capillarity values as the mixtures with only natural aggregates; (iv) the addition of fly ash is beneficial to reduce water penetration under pressure, absorbing 65% less water than the reference and the recycled aggregates have little influence on this parameter.Carbonation resistance: (i) the cement dosage has an important influence on reducing the carbonation depth, the reference mixtures being those with less carbonation; (ii) in BT, high compactness combined with slag addition proved to be an efficient mixture regarding this parameter, since despite having high cement replacement, BT250-slag presents only 46% more carbonation depth than the reference, instead of 120% for the mixtures using fly ash; (iii) MT mixtures with fly ash additions have similar effects in reducing carbonation compared to the reference, with or without recycled concrete aggregates; (iv) in MT series, slag addition, after an initial benefit, also tends to change the effect at older ages.Service life of structures exposed to carbonation: (i) higher cement dosages promote longer lifetimes, as the references present the highest values of this parameter; (ii) in XC2 environments, a service life of 100 years is ensured for all mixtures with a 15-mm cover, while in XC3 environments a 50 year service life is ensured for all mixtures with a 20-mm cover; in the XC4 environment, the same service life is, in general, ensured with a cover of 20 mm; (iv) the incorporation of recycled aggregates has a small but positive influence on concrete performance.0 values of 81% below the reference, in MT250-Poz; (iii) naturally, the inclusion of recycled concrete aggregates slightly increase the D0 coefficient; (iv) all optimized mixtures are rated with “very/extremely high” chloride penetration resistance.Chloride diffusion coefficient: (i) mixtures with type II additions show the greatest influence of pozzolanic effects and the corresponding maturity of the matrixes with age; (ii) the addition of fly ash is very advantageous for increasing the resistance to chloride migration, reducing the chloride coefficient up to 80%, in MT250-FA, at 90 days; (ii) natural pozzolan addition is also very beneficial regarding chloride resistance, presenting DElectrical resistivity of the concrete surface: (i) since this test allows a quick assessment and prediction of chloride migration, this evaluation proves to be accurate, revealing the same trend in the chloride migration test and considering the high correlation between both results; (ii) concrete with the addition of fly ash shows the highest values of this parameter, followed by concrete with the addition of pozzolans; (iii) all mixtures tend to stabilize after around 300 days.Service life of structures exposed to chloride ions: (i) pozzolanic additions highly influence the resistance to chloride penetration, which is proved by the results of mixtures with fly ash and pozzolans; (ii) to assure a service life of 50 years, both in the BT and MT series, the cover required ranges between 15 and 31 mm; (iii) the incorporation of recycled aggregates slightly increases the minimum cover and decreases the expected service life.The experimental study presented herein is focused on optimizing the mechanical and durability properties of concrete with low cement content, maximizing the compactness and combining the partial replacement of cement with a high content of fly ash, natural pozzolans, and electric furnace slags, with a 20% replacement of natural aggregates by recycled concrete aggregates. Two types of formulations were produced and characterized, BT (with dry consistency) and MT (with plastic consistency). The properties were compared to plain cement-based reference mixtures, commonly used in the prefabrication industry. Based on the analyses, the following conclusions are drawn:Finally, it is concluded that eco-efficient concrete mixtures designed with high compactness, low cement content, and a high replacement rate (up to 50%) of cement through specific additions , combined with 20% recycled concrete aggregates, still generally present improved mechanical properties. Regarding durability, depending on the exposure conditions related to corrosion risk induced by chloride ions or by carbonation, these concrete mixtures can lead to significant improvements in terms of chloride resistance and to a minor influence, or a slight decrease, in carbonation resistance, even though they have a generally long service life.


Renal interstitial fibrosis (RIF) is an important cause of kidney disease, which seriously affects people's health. As a traditional Chinese medicine, Shen-Shuai-Ling Formulation (SSLF) has obvious kidney function. However, the therapeutic effect of SSLF on RIF and its molecular mechanism are still unclear. β (TGF-β) were the indexes of renal interstitial fibrosis.  First, the potential targets and pathways of SSLF for RIF were predicted by network pharmacology, and then, the binding of luteolin and target protein to SSLF was verified by molecular docking and Co-IP experiments. Finally, the effects of SSLF and luteolin on PLZF and (Pro) renin receptor (PRR) were verified by western blot and qPCR experiments. Angiotensin (Ang)-1, Ang-2, and transforming growth factor-β. The overexpression of PLZF decreased the expression of PRR, the knockdown of PLZF increased the expression of PRR, and the overexpression of PRR decreased the expression of Ang-1, Ang-2, and TGF-β.  Through the drug-active component-target network diagram, we found that luteolin has the most connections, and promyelocytic leukemia zinc finger (PLZF) is the target protein. GO analysis and KEGG pathway analysis of targets were performed using Cytoscape ClueGO. Molecular docking experiments and Co-IP are used to prove that luteolin and PLZF can be combined. Western blot and qPCR results showed that both SSLF and luteolin significantly upregulated the expression of PLZF and decreased the levels of PRR, Ang-1, Ang-2, and TGF- SSLF inhibits PRR and renal interstitial fibers by the upregulation of PLZF levels. Chronic kidney disease (CKD) is a disease in which renal structural or functional abnormalities last longer than 3 months. RIF is a common pathological feature of CKD. RIF is the replacement of normal tissue by fibrous tissue and renal failure following chronic and persistent renal injury. Inhibition of RIF is significant in the treatment of CKD.β plays a key role in regulating the upstream factors produced by ECM. Ang-2 is of great significance in regulating TGF-β upstream factors. PRR plays an important role in regulating the production of Ang-2 [Excessive accumulation of extracellular matrix (ECM) in the kidneys is an important cause of RIF , 2. TGF-of Ang-2 . In 2002of Ang-2 , 5. PRR of Ang-2 , 7.PLZF is also known as zinc finger and BTB  domain containing 16 (ZBTB16) or zinc finger protein 145 (Zfp145). In humans, the PLZF gene is located at position 23 (11q23) of the long arm of chromosome 11, and the gene expression product is a transcription factor composed of 673 amino acids , 9. It iSSLF is a prescription developed by Xin Zheng, a master of traditional Chinese medicine with more than 60 years of clinical experience . SSLF haTo study SSLF's functional mechanism and understand its potential inhibitory role in renal fibrosis, we first predicted the possible targets and pathways of SSLF for renal fibrosis using network pharmacology molecular docking, and then, we used molecular docking and Co-IP experiments to verify the binding of SSLF and its luteolin to target proteins. Finally, western blot and qPCR experiments were used to find the mechanism of SSLF and luteolin in inhibiting renal fibrosis.SSLF is composed of Herba Rhubarb (DH), Herba Codonopsis pilosula (DS), Herba Astragalus membranaceus (HQ), Herba Stony dragon (ML), Herba Safflower (HH), Herba Ganoderma lucidum (JLZ), Herba Angelica sinensis (DG), Herba Salvia miltiorrhiza (RS), Herba Epimedium (YYH), and Herba Dandelion (PGY). SSLF used in our research was processed by the Chongqing Institute of Traditional Chinese Medicine .β and 100 nM renin for 24 hours.Human kidney 2 (HK-2) cells were purchased from the American Type Culture Collection (ATCC) . HK-2 cells were cultured in DMEM/F12 medium (Gibco). In addition, ten 6-week-old male SD rats were given 20 mg/kg SSLF intragastrically for 7 days. The animal experiment was approved by the Animal Ethics Committee of the Chongqing Hospital of Traditional Chinese Medicine. Rats were euthanized, and serum was collected on day 8. HK-2 cells were seeded and exposed to drug-containing serum or blank serum for 24 hours. HK-2 cells were treated with 10 ng/ml TGF-http://www.swisstargetprediction.ch/. The genes related to human RIF were selected from the GeneCards (https://www.genecards.org/) disease database. The PPI network was constructed by STRING database (https://string-db.org/), and the drug-component-target network was constructed by Cytoscape 3.6.0. The GO analysis and KEGG pathway analysis were performed on 86 target sites with Cytoscape ClueGO, and the enrichment analysis results were visualized.The active components of SSLF were retrieved from the website https://tcmspw.com/tcmsp.php), the 3D structure of the key target protein was retrieved from the Protein Data Bank (http://www.rcsb.org/pdb), the receptor protein was hydrogenated by AutoDock 4.2.6 software, the charge was calculated, and the receptor protein and ligand molecules were molecularly docked by AutoDock Vina 1.1.2. The confirmation was obtained by docking, the binding energy was scored, and the best binding energy was obtained for graph analysis. PyMOL was used as a three-dimensional graph to show the interaction between the receptor protein and a small molecule of ligand.The 3D structure of luteolin was obtained from the TCMSP , then transferred to a PDVF membrane, closed with 5% skim milk for 1 h at room temperature, and washed 3 times with TBST, 5 min each time. 3% BSA primary antidilution solution was diluted with 1 : 1000∼2000, incubated at 4°C overnight, and incubated with secondary antidilution solution (1 : 1000) for 1 h on the next day.Luteolin was labeled with biotin by EZ-LinkTM Biotin-LC-Hydrazide (Thermo Scientific). After 24 h incubation, the cells were collected by centrifugation and precooled RIPA buffer was added. The suspension was centrifuged for 15 min. The protein A agarose beads were added and centrifuged for 15 minutes to remove the protein A agarose beads. Add rabbit anti at 4°C overnight. Protein A agarose beads were added to capture the antigen-antibody complex at 4°C overnight. Agarose beads-antigen antibody complexes were collected by centrifugation. The samples were boiled for 5 min. After boiling, the samples were detected by SDS-PAGE electrophoresis.−∆∆CT algorithm. Primer sequence of each gene is as follows: PLZF-F(GCTACTGTGCAAGGCCAACCA), PLZF-R(GCGGTGGAAGAGGATCTCAAACA), PRR-F(GGTAGGGAAGGCAAACTCAGTG), PRR-R(ATTGAGGGGGAGTGAACTGAGAAC), Ang-1-F(AAGATTGCTTCAGCCAGCGTC), Ang-1-R(AGGTGACTTTGGCTACAAGCATTGT), Ang-2-F(TTCAACCTCGCTGTGGCTGA), Ang-2-R(AACTTTGCACATCACAGGTCCAA), TGF-β1-F(AATACAGCAACAATTCCTGGCGA), TGF-β1-R(CGCACAACTCCGGTGACATCAAA), GAPDH-F(CTGGGCTACACTGAGCACC), and GAPDH-R(AAGTGGTCGTTGAGGGCAATG).Total RNA was extracted from the sample using TRIzol reagent . cDNA was reverse-transcribed using the PrimeScript TM RT kit . The response system and procedures for qRT-PCR are described in the instructions of the TB Green Premix Ex Taq II , using the CFX96 Real-Time System . The relative expression level of genes was calculated by the 2t-test, and the mean of multiple groups of samples was analyzed by one-way ANOVA (p < 0.05). All the experiments were repeated three times independently, and the results are expressed as the mean value ± standard deviation.SPSS 23.0 was used to analyze the data. The mean of two groups of independent samples was compared by In order to study the role of SSLF in RIF, we first predicted 747 targets of SSLF active components in the SwissTargetPrediction database, screened 414 targets of RIF-related genes in the GeneCards database, and obtained 86 intersection genes by intersection analysis . Then weIn order to explore the function of SSLF and the role of potential targets in signaling pathways, we used Cytoscape ClueGO to analyze 86 targets by GO and KEGG pathway and visualized the enrichment analysis results. The GO enrichment analysis shows that, in biological process (BP), it is related to acute inflammatory response, hormone metabolic process, positive regulation of protein localization to the membrane, and negative regulation of gene silencing by RNA . In moleIn order to investigate the effect of luteolin in SSLF on PLZF and core target protein, we first select the key component luteolin and core target genes AKT1 (PDB ID : 1UNQ), VEGFA (PDB ID : 3V2A), STAT3 (PDB ID : 4ZIA), and PLZF (PDB ID : 1BUO) for molecular docking. The binding energies of luteolin and core target proteins were 5.58 kcal/mol (AKT1), 5.25 kcal/mol (VEGFA), 4.08 kcal/mol (STAT3), and 6.48 kcal/mol (PLZF). The amino acid residues  of luteolin and PLZF form hydrogen bonds. The amino acid residues of luteolin and PLZF  form hydrophobic interactions Figures . To veriβ. The qPCR results were consistent with the western blot results  and the second group was medium-dose SSLF (40% of rat serum concentration). The third group was high-dose SSLF (60% of rat serum concentration). The effect of SSLF sum on PLZF was detected by western blot experiment and qPCR experiment. The western blot results showed that SSLF significantly upregulated the expression of PLZF and decreased the levels of PRR, Ang-1, Ang-2, and TGF- Figures . Similar Figures . Recentlβ were consistent with those of PRR  , 12. EndTo study SSLF's functional mechanism and understand its potential inhibitory role in renal fibrosis, first, we found that STAT3, VEGFA, and AKT1 of the intersection genes of SSLF and RIF are the core proteins in the intersection genes. Using the SSLF-compound-target-RIF network, we found that luteolin, the monomeric drug, has the most connections, and PLZF is the target protein. In order to study the effect of SSLF on PLZF, we used molecular docking and IP experiments to find that the key component of SSLF, luteolin, can bind to PLZF. At present, the mechanism of transcriptional inhibition of PLZF is that PLZF binds to the promoter of the target gene through nine zinc finger structures at the C-terminal, and then its N-terminal BTB/POZ domain recruits nuclear coinhibitory complexes. The physiological functions of PLZF mainly include regulating the differentiation of hematopoietic cells, maintaining the stability of the hematopoietic progenitor cell pool, maintaining the normal development of bone and the renewal of male germ cells, participating in the development of nerve cells, regulating the cell cycle, and participating in cell growth, proliferation, differentiation, and apoptosis. Recent studies have shown that PLZF also participates in immune response and has environmental-dependent anticancer and antitumor effects –21.β is the most effective factor affecting ECM accumulation, which can stimulate ECM production and inhibit ECM degradation. Ang-2 is a member of RAS, and RAS is one of the important pathways closely related to TGF-β. The classical RAS is mainly the conversion of renin to Ang-2. Renin is an important hormone secreted by RAS, which can catalyze the conversion of angiotensinogen to Ang-1, and Ang-1 is subsequently cleaved by ACE to Ang-2. It is found that injection of Ang-2 in rats can increase the expression of glomerular TGF-β, and blocking the activity of Ang-2 can significantly reduce the expression of TGF-β, reduce the formation of ECM, and effectively slow down the progression of disease [TGF- disease , 23. It  disease . PRR is  disease , 26.β reduced the PLZF levels and inhibited PRR and other indices of renal interstitial fibrosis. To verify that PLZF affects renal interstitial fibrosis by regulating PRR, we overexpressed PRR, and western blot and qPCR results showed that, in HK-2 cells, PRR significantly increased the levels of other indices of renal interstitial fibrosis, suggesting that PLZF does inhibit renal interstitial fibrosis by inhibiting PRR expression.To investigate whether SSLF regulates PLZF, we first used renin to induce fibrosis in HK-2 cells. Then, western blot and qPCR experiments showed that SSLF could significantly upregulate the expression of PLZF and decrease the expression of PRR and other indices of renal interstitial fibrosis. Then we also found that luteolin, a key component of SSLF, could upregulate the expression of PLZF and reduce the expression of PRR and other renal interstitial fibrosis markers. The present study found that renin-treated HEK293 cells resulted in nuclear translocation of PLZF, and then PLZF was recruited to the promoter of the PRR gene. We then found that overexpression of PLZF inhibited PRR levels and other indices of renal interstitial fibrosis using western blot and qPCR in a renin-induced model of renal interstitial fibrosis. The knockdown of PLZF resulted in a significant increase in the PRR levels in cells and a significant increase in other indices of renal interstitial fibrosis, and qPCR also validated the same conclusion. This suggests that PLZF can indeed regulate PRR expression. In addition, we found that TGF-We first predicted the possible targets and pathways of SSLF for RIF using network pharmacology, and then we used molecular docking and IP experiments to verify the binding of SSLF and its key component, luteolin, to target proteins. Finally, using western blot and qPCR experiments, we found that SSLF and luteolin could upregulate the expression of PLZF and inhibit the level of PRR. In future studies, we will further verify the effect of SSLF and luteolin in regulating renal interstitial fibrosis through PLZF in animal models and collect clinical data to analyze the relationship between the consumption of SSLF and the expression level of PLZF in the body to provide a basis for better clinical applications.


There is an increasing trend on the practices of parental self-medication with antibiotics (PSMA) around world, accelerating the antibiotic abuse. This study aims to examine the nationality differences in the practices of PSMA and knowledge, attitudes and practices (KAP) toward antibiotic use, and understand the practices of PSMA among parents of various nationalities in China.A cross-sectional study based on a structured questionnaire survey was conducted in Xi’an, Shaanxi Province, China, from September 2018 to October 2018. A total of 299 respondents participated in. The practices of PSMA (a dichotomous variable) and KAP toward antibiotic use (a continuous variable) served as dependent variables. Participant’s nationality was regarded as the independent variable. Binary logistic regression and ordinary least square regression were employed to examine the association between parent’s nationality and the practices of PSMA, and KAP toward antibiotic use, respectively.121 (40.88%) Chinese, 100 (33.76%) other Asians and 75 (25.34%) Occidentals were included in final analysis, with a sample size of 296. Chinese were more likely to practice PSMA , with worse knowledge , attitudes  and practices  toward antibiotic use, compared to their Occidental counterparts. The main reasons for the practices of PSMA were enough previous medication experience (80.49%) and same ailments with no need to see a doctor (39.02%), with common symptoms such as fever (60.98%) and cough (58.54%). Purchasing antibiotics at pharmacies (92.08%) and using leftover antibiotics (26.83%) were usual approaches.The study highlights the gaps in the practices of PSMA and KAP toward antibiotic use among parents of different nationalities. The access to obtain antibiotics from pharmacies reflects the pharmacists’ unaware of laws on prescription of antibiotics, fierce competition in the pharmacy market, and the government’s lax supervision in China. It suggests the need to improve pharmacists’ training, enforce current legislations on pharmacy market regarding the sale of antibiotics, and provide practical and effective educational interventions for residents about antibiotic use.The online version contains supplementary material available at 10.1186/s41256-021-00226-y. Bacterial resistance, a main adverse effect of antibiotic use, is mainly driven by irrational and excessive use of antibiotic in both communities and clinical settings . It is rThere is an increasing trend on practicing self-medication with antibiotics (SMA) in both developed and developing countries in recent years, which is one of the most dangerous and prevalent inappropriate antibiotic use behaviors . A systeIn practice, SMA also includes the medication for family members, in particularly, the therapy for children or the old . PreviouUnlike high-income countries, non-prescribed antibiotics (NPA)  are easAs we all know, the irrational or overuse of antibiotics is caused by either health service supplier or demander. The supply side factors mainly include the lack of supervision , corruptIn the current study, we aim to (1) explore the association between parent’s nationality and the practices of PSMA; (2) examine the nationality differences in KAP toward antibiotic use; (3) understand the practices of PSMA among parents of various nationalities living in China.This was a cross-sectional study conducted in Xi’an Hi-Tech International School, International Department (XHISID), Shaanxi Province, China, for a period of 2 months from September 2018 to October 2018. XHISID was founded in 2003. It is the first International Baccalaureate (IB) World School authorized by the IB Organization in the northwest region of China, also a key international education program supported by the Hi-Tech Zone Administrative Committee of Xi’an, Shaanxi. XHISID has more than 300 students from about 15 countries around the world. It is a 15-year consistent school. School offers the IB-Primary Years Programme, IB-Middle Years Programme and the Diploma Programme continuum from kindergarten to high school. It is the only SAT and AP test center authorized by the American College Board in the northwestern region of China. XHISID provides a non-profit education focused on enabling confident, open-minded global citizens through life-long learning and a sense of community.The sample size was calculated using Raosoft , an onliThe survey was conducted at classrooms after parents meeting. Participants were eligible to be included if they: (1) being a parent whose child was studying at XHISID; (2) having no hearing or visual disorder; (3) being literate; (4) volunteering to participate in. An introduction to study purpose, significance and privacy safety was informed to participants by our investigators before the investigation. Respondents were required to self-complete questionnaire with their informed consent. Finished questionnaires were collected by the investigators on the spot. A total of 299 individuals participated in the investigation and accomplished questionnaire.The questionnaire was developed by reviewing applicable comparable studies , 45–49 a296 individuals were eventually analyzed excluding the missing values. PSMA served as a dependent variable in this study, measured by question, “Did you self-medicate your child with antibiotics in the past 6 months”, with an answer of “No” or “Yes”, coding 0 and 1. Another dependent variable was KAP toward antibiotic use. Antibiotic knowledge was composed of 6 questions, with an answer of “True”, “False” and “Not sure”. We classified the answer into “Wrong” (including incorrect answers and “Not sure”) and “Right” (correct answers), coding 1 and 2. The sum score ranged from 6 to 12, with higher score indicating better antibiotic knowledge. Antibiotic attitudes consisted of 14 items. Each item is answered on a five-point Likert scale , coding from 1 to 5. A total scale score was computed by summing item scores, with a range of 5 to 25. Higher scores indicated better antibiotic attitudes. Practices of antibiotic use were measured by 12 items with a five-point Likert response (“Always” to “Never”), coding from 1 to 5. Item scores were summed and converted to a scale ranging from 6 to 30, with higher scores presenting better antibiotic behaviors. The total antibiotic score was the sum of the above scales, ranging from 17 to 67, where higher values indicated better antibiotic perceptions.Parent’s nationality was an independent variable, with a category of Chinese, other Asian and Occidental. Control variables included parent’s gender , age , education level  and income , having medical staff or not in family , child’s age  and gender , the only child or not  and having medical insurance or not . In addition, total antibiotic score  was controlled when examining the association between parent’s nationality and the practices of PSMA.P value was at the significance level α = 0.05.The data was entered into a database using the Epidata 3.1, and transferred to Stata statistical software  for all analysis. One-way ANOVA and Kruskal–Wallis test were used to compare KAP toward antibiotic use among parents of different nationalities. The association between parent’s nationality and the practices of PSMA was examined using the binary logistic regression model adjusted for socio-economic characteristics of parents and children, and antibiotic score. Ordinary least square (OLS) regression controlling for socio-economic characteristics of parents and children was employed to examine the association between parent’s nationality and KAP toward antibiotic use. The response rate was 84.57%. As Table P < 0.001).It was found that 13.85% of the respondents practiced PSMA in the past 6 months. The prevalence of PSMA among Chinese was higher than that among other Asians and Occidentals . With regard to the perception of antibiotic use, Occidental parents still performed better than Chinese, followed by other Asians .KAP toward antibiotic use among parents of different nationalities are showed in Table The results of regression analyses examining the association between parent’s nationality and the practices of PSMA, and the association between nationality and KAP toward antibiotic use are conducted and presented in Table To our knowledge, this is the first study to understand the practices of PSMA, and KAP toward antibiotic use among parents of various nationalities under Chinese health system. Our results demonstrated that: (1) Chinese were more likely to practice PSMA, and performed worse KAP toward antibiotic use, compared to their Occidental counterparts; (2) the practices of PSMA occurred for symptoms such as fever and cough, mainly because of previous medication experience and the same ailments with no need to see a doctor; (3) the common sources of antibiotic information included previous medication experience, and the recommendations from relatives, friends and pharmacy personnel; (4) antibiotics for self-medication were often obtained from pharmacies and leftover of previous medication.It is well known that unnecessary and irrational use of antibiotics is a major cause of bacterial resistance , which iThe practices of PSMA difference among parents of various nationalities could be explained by KAP toward antibiotic use that parents performed. The finding outlined significant gap in KAP among parents of different nationalities, indicating that Occidental parents performed better than Chinese, which is less confounded by healthcare provider factors as they lived in the same city under the same health system. Several studies state that the control of irrational use of antibiotics is mainly dominated by regulation of physician prescription and correct KAP toward antibiotic use , 58. PleRegarding the antibiotics for self-medication, previous studies showed that they were usually obtained from over-the-counter purchases at retail pharmacies and leftover medications from previous prescriptions , 62, in Nowadays, driven by the fact of aggressive marketing strategies and high expectations for antibiotics, antibiotics are often mistaken used to treat self-diagnosed non-bacterial diseases and viral infections. Children suffering from the Upper Respiratory Tract Infection (URI) with symptoms of fever, cold, cough and sore throat are more likely to be self-medicated with antibiotics –70. FurtWe acknowledge several limitations of this study that need to be addressed in future studies. Firstly, this study is limited in the sample population conducted in an International School, resulting in inadequate sample size. Participates are much richer and better educated than general populations because of the convenience sampling, which leads to the selection bias and cannot be well generalized to the whole population of different nationalities. Secondly, self-administered questionnaire can be subject to social-desirability bias, leading to untrue feelings and practices. Thirdly, participates’ medical insurances are not identified in this study. Different type of medical insurance coverage may lead to different health seeking behavior and the practices of PSMA. Fourthly, local Chinese may be more familiar with health system and easier to get access to antibiotics compared to non-Chinese, although they both live in the same city for a long time. Fifthly, the lack information of grandparents of the children may underestimate the practices of PSMA, since grandparents are also the main caregivers for children . In addiThe study highlights the gaps in the practices of PSMA and KAP toward antibiotic use among parents of various nationalities, indicating that Chinese are more likely to practice PSMA, with worse KAP toward antibiotic use, compared to their Occidental counterparts. The access to obtain antibiotics from pharmacies reflects the pharmacists’ unaware of laws and regulations on prescription of antibiotics, fierce competition in the pharmacy market and the government’s lax supervision in China. These findings suggest the need for Chinese health sector and government not only to strengthen the supervision and regulation on pharmacy market regarding the sale of antibiotics, but also improve pharmacists’ training, and provide practical and effective educational interventions for the public about rational use of antibiotics via doctor-patient communication, brochures, poster, lectures and Internet, to discourage the practices of PSMA.Additional file 1: Questionnaire of parental self-medication with antibiotics among parents of different nationalities (English Version).Additional file 2: Questionnaire of parental self-medication with antibiotics among parents of different nationalities (Chinese Version).