The study aims to investigate the fire performance of reinforced concrete (RC) slab fabricated from high volume fly ash inclusion with nano-silica (HVFANS) under ISO 834 load curve. The HVFANS concrete slab with dimensions of 1850 mm × 1700 mm × 200 mm was tested via an electrical furnace under an exposing temperature of 1100 °C for 120 min. The slab behaviour was evaluated in terms of residual compressive strength, temperature distribution along its thickness, spalling, and cracks. The results revealed that the slab was capable of maintaining 62.19% of its original compressive strength at room temperature after exposure to the above temperature. Moreover, the distribution of temperature revealed that the temperature of concrete cover and bottom reinforcement was less than 300 °C with a maximum spalling depth of 11 mm within the temperature range of 680 to 840 °C. Furthermore, the thermal conductivity index (K) of the HVFANS concrete was determined, and results indicated that thermal conductivity equalled 0.35 W/mK which is considered low, as compared with other concretes tested in current and previous studies. Fire represents one of the most severe conditions to which structures might be subjected as the instant the catastrophic fire of the Mont Blanc tunnel in 1999s which caused 39 deaths and serious damage to the tunnel lining structure that cost €206 to €250 million for restoration work . In the 3 could significantly improve the spalling resistant of HSC due to the melting of PPF between 160 to 170 °C and evaporation at 350 °C caused new pores which work as channels to relieve the internal energy of water vapour pressure [Engineering structures are usually constructed from normal strength concrete (NSC) or high strength concrete (HSC) fabricated by various procedures ,7. Studipressure ,16,17,182 which contributed about 65% of global warming [Nowadays, the massive production of Portland cement resulted in significant growth in environmental pollution. Several reports stated that the manufacturing of one ton Portland cement liberated around one ton of gases to the atmosphere, mainly composed of carbon dioxide CO warming ,20,21,22 warming .In this field, several scholars aimed to use fly ash which is a by-product of thermal electric plants as a partial replacement of Portland cement due to its beneficial effects on the concrete behaviour and low cost. Moreover, they intensively studied the effects of using FA on the thermal properties of concrete. Bentz et al.  reportedThe main shortcoming of using high volumes of fly ash in concrete is the sharp reduction in the compressive strength at early ages as indicated by several researchers ,30,31,32Moreover, researchers noted that the addition of NS considerably improved the thermal stability of the HVFA concrete. Lim et al.  indicateAccording to the above results, this study aims to test the fire performance of HVFANS concrete as a part of the structure to increase the confidence of using this type of concrete in engineering structures. Therefore, a concrete slab with dimensions of 1850 mm × 1700 mm × 200 mm was fabricated according to the mix proportions recommended by Ibrahim  and test2, aluminium oxide Al2O3, and ferric oxide Fe2O3 must be more than 70% [The Portland cement (Type I) manufactured by Tasek Cement Company  according to Malaysian standard (MS 522)  was usedthan 70% . The chethan 70% .2/g, with an average size of 35 nm, and a silica concentration of 50%, with a bulk density of 1050 kg/m3 and pH of 10. Natural river sand was used as a fine aggregate which could pass through a 4.75 mm sieve size with a bulk specific gravity of 2.53 and fineness modulus of 2.98 [2.Colloidal nano-silica (NS) type Cembinder W8 provided by AkzoNobel Company  was used to enhance the early compressive strength of concrete, thereby shortening the setting time of the cement slurry . The sur of 2.98 ,42. The  of 2.98 . Crushed3 of concrete volume and length of 12 mm with a specific gravity of 0.9, were added to increase the ductility of concrete and reduce the surface spalling, as recommended in prior studies [Superplasticiser type (Darex Super 20) manufactured by GCP Applied Technologies company  was added with a dosage of 1% of cementitious materials weight to provide the required workability and improve the compressive strength of concrete via decreasing the amount of water in the mixture due to the existence of naphthalene sulphonate ,45,46. W studies ,15,16,17The mixture proportions of plain concrete (PC) and HVFANS concrete slabs with a target compressive strength of 60 MPa were selected based on the American Concrete Institute Standard (ACI 211.4R-93) , as descThe mixing of materials based on ASTM C192  led to tTwo slabs were fabricated from plain concrete (PC) and HVFANS concrete, each with a size of 1850 mm × 1700 mm × 200 mm, according to the European Federation of National Associations Representing Concrete (EFNARC) . During The fire test was conducted by using a medium-scale furnace provided by Forest Research Institute Malaysia (FRIM)  with dimensions of 1.5 m × 1.5 m × 1.5 m at a temperature of 1100 °C, as shown in The heat within the chamber was controlled at the standard heating temperature according to the ISO 834 fire curve. The temperature was measured at 100 mm from the furnace wall to ensure compliance with the fire load curve. The opening of the furnace was wrapped by a fireclay rock wool sheet to avoid thermal loss. The concrete slab was placed horizontally at the top of the furnace opening. The test setup of the fire test included the position of the concrete slab and thermocouple wire connected to the data logger and computer, as shown in t is the time in min, and Tt) and thermal conductivity (K) are computed using the following equations:T is the temperature difference, A is the surface area, Q is the total heat supplied, and d is the specimen thickness. The measurement was computed at a single temperature of 20 °C at a temperature difference of 15 K.The thermal conductivity test of PC and HVFANS concrete was carried out by using the λ-Meter EP500e tool manufactured by Lambda-Meßtechnik GmbH Dresden  based on Malaysian Standard ISO 8302 . AccordiThe coring tests for PC and HVFANS concrete slabs were conducted before and after the fire test according to ASTM C42 guidelines which recommended that the ratio of specimen length to its diameter (L/D) should range between 1.9 to 2.1 . TherefoThe thermal conductivity of PC and HVFANS concrete was determined. The results demonstrated that the HVFANS concrete had a lower thermal conductivity equal to 0.35 W/mK, as compared with PC, which recorded 0.8 W/mK at similar test circumstances. This behaviour might be attributed to the existence of high-volume fly ash, whereas Bentz  recordedDuring the fire test, the thermal distribution of PC and HVFANS concrete slabs was recorded via four thermocouples located at different depths from the heated surface, as shown in Further comparison was conducted with previous slabs tested by other scholars under similar temperature magnitudes, reaching up to 1100 °C, which particularly occurred in concrete tunnels ,53. The The concrete spalling effect was carefully observed and recorded during the furnace test for both concrete slabs. The results showed a spalling location on the heated surface of the HVFANS concrete slab with a maximum depth of 11 mm and area of 34.3% within the temperature range of 680 to 840 °C, while the PC slab recorded the highest spalling depth of 19 mm within a lower temperature range of 480 to 700 °C, as shown in The moisture content of both concrete slabs was recorded before and after the fire test. The average records of the cores for PC and HVFANS concrete before the fire were 4.95 and 5.97%, respectively. The moisture content was reduced after firing for both concrete slabs and recorded 4.10 and 5.40%. The water was vapoured out from visible cracks distributed along the width of the unexposed concrete slab surface as well as along the installation holes of the thermocouples and reinforcement within the time range between 20 to 100 min. Similar phenomena were observed by previous scholars ,60,61,62The average compressive strength of two cylindrical coring samples was recorded before and after the firing of PC and HVFANS concrete slabs. The results revealed that the compressive strength of both slabs was decreased after exposure to elevated temperatures reaching up to 1100 °C. However, the HVFANS slab showed superior fire resistance and recorded the lowest reduction, by −37.81%, as compared with the PC slab which recorded a reduction of −63.42%, as shown in Moreover, the reduction and relative compressive strength (RCS) was computed for both concrete slabs by the following equations:The results proved that the HVFANS slab had the highest RCS by 62.19%, as compared with PC which recorded only 36.58%. Ibrahim et al. [From the above core samples, the density of PC and HVFANS concrete slabs were determined before and after the fire test according to ASTM C138 . The resA rebar tensile test was performed to determine the yield strength of steel reinforcement before and after the fire test. The yield strength of mild steel reinforcement used in the HVFANS slab almost remained constant, with a value of 276.29 MPa between temperatures of 28 to 283 °C, as shown in The mechanical properties of the steel reinforcement deteriorated when subjected to temperatures exceeding 300 °C . The resVisual inspection showed that minor spalling occurred in the concrete slab with a maximum depth of 11 mm at a duration between 10 to 30 min within a temperature range of 680 to 840 °C while severe spalling occurred in the PC slab with a depth of 19 mm within temperatures range of 480 to 700 °C;The coring test indicated that the residual compressive strength of the HVFANS concrete slab was reduced by −37.81% from its original compressive strength under 1100 °C, while the strength of the PC slab was reduced by −63.42% under similar circumstances;The temperature distribution along slab thickness indicated that the HVFANS concrete had superior performance and recorded lower temperatures than the PC slab under all the investigated depths;The yield strength of mild steel reinforcement into the HVFANS concrete slab almost remained constant with a value of 276.29 MPa between temperatures of 28 to 285 °C, while the strength of similar reinforcement into the PC slab was reduced to 216.29 MPa under identical conditions;K) of 0.35 W/mK, which is considered lower than other concrete types such as NSC and HVFA concrete types.The thermal conductivity test results proved that HVFANS concrete had excellent fire resistance with a maximum thermal conductivity value (The results can be summarised as follows:According to the above results, the HVFANS concrete can provide superior fire protection, as compared to plain concrete, for the structural members exposed to massive temperatures reaching up to 1100 °C. Therefore, future studies are recommended to present further information about this type of concrete.


Synthetic lethality (SL) is a promising gold mine for the discovery of anti-cancer drug targets. Wet-lab screening of SL pairs is afflicted with high cost, batch-effect, and off-target problems. Current computational methods for SL prediction include gene knock-out simulation, knowledge-based data mining and machine learning methods. Most of the existing methods tend to assume that SL pairs are independent of each other, without taking into account the shared biological mechanisms underlying the SL pairs. Although several methods have incorporated genomic and proteomic data to aid SL prediction, these methods involve manual feature engineering that heavily relies on domain knowledge.Here, we propose a novel graph neural network (GNN)-based model, named KG4SL, by incorporating knowledge graph (KG) message-passing into SL prediction. The KG was constructed using 11 kinds of entities including genes, compounds, diseases, biological processes and 24 kinds of relationships that could be pertinent to SL. The integration of KG can help harness the independence issue and circumvent manual feature engineering by conducting message-passing on the KG. Our model outperformed all the state-of-the-art baselines in area under the curve, area under precision-recall curve and F1. Extensive experiments, including the comparison of our model with an unsupervised TransE model, a vanilla graph convolutional network model, and their combination, demonstrated the significant impact of incorporating KG into GNN for SL prediction.https://github.com/JieZheng-ShanghaiTech/KG4SL.: KG4SL is freely available at Bioinformatics online.Supplementary data are available at  Complex biological systems cannot be composed by a large number of genes acting independently, but rely on the interactions between genes which can be further classified into enhancing and suppressive effects . The supin silico knockouts using metabolic network models. A spectrum of computational methods has been proposed for SL prediction. These methods can be categorized into three classes. The first class involves simulating 2MF  might latently invalidate the assumption of independency. For instance, poly (adenosine diphosphate-ribose) polymerase 1 (PARP1) and breast cancer 1 (BRCA1) are a famous SL gene pair, leading to the first clinically approved SL-based cancer drug, PARP inhibitor . PARP1 a2MF and GRSMF] have injected some genomic and proteomic data to facilitate the SL prediction, and the results of these studies have underscored the significance of integrating additional information. Meanwhile, GNN-based methods can also encode such information as input features. However, these methods extracted features manually based on domain knowledge and some features might be left out. Therefore, to attain a more comprehensive set of features to improve the performance of SL prediction, we need a new method capable of automatic knowledge integration and feature extraction.A subset of existing methods [e.g. SVM, random forests (RFs), SLE are defined as triplets Knowledge graphs (KGs) are a type of multi-relational graph, where nodes and edges have different types. A KG is denoted by wo nodes . By incoHere, we propose a novel KGNN-based method for SL prediction, named KG4SL, which utilizes KG MP as a back-end. We approach the independency issue by injecting various factors including biological processes, diseases, compounds etc. that could be pertinent to SL, into our KG. Our model comprises three parts. In the first part, we derive a gene-specific subgraph from the original KG for each gene. In the second part, we conduct MP on the gene-specific subgraph, to automatically associate genes with factors that could be decisive in identifying an SL pair. In the third part, we define a decoder to reconstruct gene–gene similarity in a supervised fashion. To the best of our knowledge, this is the first framework to integrate KG with GNN for SL prediction. We compared our model with 10 state-of-the-art methods for SL prediction, and our model outperformed all the baselines in area under ROC curve (AUC), area under precision-recall curve (AUPR) and F1. Another contribution of our work is that we studied the impact of KG, which suggests that introducing a KG combined with MP process in GNN can significantly improve the performance of SL prediction.In this section, we first introduce the data and the problem of SL prediction. Then, we present the details of the proposed KG4SL model.http://synlethdb.sist.shanghaitech.edu.cn/v2/#/; SynLethDB ,  and . And the other 8 relationships are associated with drug and compounds. Besides, 7 out of 11 kinds of entities are directly related to genes, i.e. pathway, cellular component, biological process, molecular function, disease, compound and anatomy. They are in the format of . These entities can be reached from genes in one hop, whereas the other three kinds of entities  can be reached from genes in two hops. After removing isolated nodes, the final graph of SynLethKG contains 54 012 nodes and 2 231 921 edges as shown in The 24 relationships in n is the number of genes involved in the SL pairs. In this SL matrix S, an entry ie and gene je, and 0 otherwise. Note that gene pairs with entry value 0 are unknown pairs, some of which could be potential SL pairs not yet discovered. The KG SynLethKG is denoted by eV and a set of relationships rV. Each edge in the KG is defined as a triplet r between head entity h and tail entity t, where Formally, the SL data can be modeled as a matrix S and the KG G, the problem we aim to solve is to predict the SL relationship between gene ie and gene je. To achieve this goal, we propose a GNN-based model to learn a scoring function ie and gene je is an SL pair, where W, A and b denote the learnable parameters in function F.Given the SL matrix The overall framework of KG4SL is laid out in 2.3.1Given an SL-related gene, we first construct a weighted subgraph from the KG. Identifying relevant nodes and determining the edge weights are two key operations to construct the gene-specific weighted subgraph.e is the central node/entity and N(e) is the set of neighbors of e (i.e. entities directly connected to e). In SynLethKG, the size of N(e) varies greatly among the entities. For example, network hubs may have thousands of relations, whereas some nodes are less studied and thus have a limited number of neighbors. In this work, we sample a fixed number of k neighbors for each entity to characterize its local structure and we repeat this process for H hops . An example of 2-hop subgraph with neighbor sampling size k = 4 in each hop can be seen in Assume that ie, je), the weight for an edge i’es subgraph is computed by e is one of the entities in the subgraph of ie, and je and relation g is an inner product function. Here, je.In a gene-specific subgraph, we can assign different weights for edges to describe the importance of the relations. For an SL pair ; hyper-parameters α,d, k, h and epoch;Output:  1: Initialization:eW;2: entity embedding matrix rW;3: relation embedding matrix 4: step ← 0;5: while step < epoch do6:   for  doGene-specific Subgraph(ie);7:    Gene-specific Subgraph(je);8:    9:    for m do10:     11:     for h = 1,2,…,H do12:      for  do13:       14:       15:      end for16:     end for17:     18:    end for19:    Compute the predicted probability 20:    Compute the loss 21:   end for22:   step ← step + 1;23:  end whileIn this section, we first introduce the state-of-the-art baseline methods and their implementation details, and then we compare our model with the baselines, followed by an analysis of the influence of the KG. The KG4SL model was implemented with Python 3.6 and Tensorflow 1.15.0. We adopt AUC, AUPR and F1 as the evaluation metrics.3.1.1We compare KG4SL with the following baselines:2MFSL  (rk (GCN)  is the mGraphSAGE , RW-based baselines  and GNN-based baselines . We evaluated DeepWalk, Node2Vec, LINE using CogDL  into the GNN model. Many existing methods view each SL pair as an independent sample from a latent representation, but this assumption is an oversimplification in the biological context of cancer cells. KG can bring additional information such as biological processes which could be crucial for discovering new SL pairs. By injecting the KG, our model was capable of harnessing the aforementioned issue, without manual feature engineering. Extensive experiments have been conducted to examine the impact of KG. The results show that both KG and MP in GNN are essential for boosting the model performance. Therefore, KG4SL represents a breakthrough in applying supervised machine learning to SL prediction.Our future work will focus on the following directions. First, we plan to further improve our model, using the strategy of contrastive learning, which is a self-supervised approach to learn graph representation. Secondly, the degrees of some nodes in a KG might be very large, while sampling a fixed-sized neighborhood may not fully capture the neighborhood topological structures of the nodes. To address this issue, it will be a highly desirable future work to contrast multiple receptive fields for a given node, to learn a more robust and enriched embedding. Moreover, inspired by the recently proposed KG attention network . By insp


Irrational and inappropriate antibiotic prescription is a worldwide phenomenon – increasing the threat of serious antibiotic resistance. A better understanding of health care providers' knowledge, attitudes, and prescription practices related to antibiotics is essential for formulating effective antibiotics stewardship programmes. The aim of the present study was to assess knowledge, attitudes, and prescription practices toward antibiotics among health care providers.A descriptive cross-sectional study was conducted between March and June 2017 to assess knowledge, attitudes, and prescription practices toward antibiotics among health care providers in the Rombo district of northern Tanzania. A total of 217 health care providers were interviewed using a structured questionnaire.Over half of health care providers  strongly agreed that the inappropriate prescription of antibiotics puts patients at risk. More than half  reported that their decision to start antibiotic therapy was influenced by a patient's clinical condition, while 110 (50.7%) reported they were influenced by positive microbiological results in symptomatic patients. Almost two-thirds of the health care providers  reported that they had access to and used antibiotic therapy guidelines. Less than a quarter  received regular training and education in antibiotic prescription practice in their work place.Knowledge and prescription practice of antibiotics among health care providers was generally unsatisfactory. Training and education for health care providers is needed in the area of prescribing antibiotics. In most parts of the world, antibiotic prescription practice and use is either irrational or inappropriate – increasing the threat of serious antibiotic resistance.7 and the magnitude varies widely. A recently published cross-sectional study assessed the rational prescription of medicines in 4 regions of Tanzania by studying 2,067 prescriptions from 67 health care facilities.6 The study revealed that more than two-thirds (67.7%) of the prescriptions were antibiotics, when compared to the optimal level of 30%, indicating that overprescribing antibiotics is a prevailing behaviour among health care providers. More alarming results were reported by an earlier study in the Northern Zone of Tanzania among 384 children – aged 1 month to 5 years being managed for acute watery diarrhoea – where 84.9% were given antibiotics.7 Since most acute watery diarrhoea in that region is caused by viruses, antibiotics should not have been prescribed. The results of these studies, conducted in the same region where the present study was conducted, underscore a need to assess the levels of knowledge and attitudes of the health care providers regarding prescription practices of antibiotics.In Tanzania, studies have indicated that irrational prescription patterns of antibiotics by health care providers is a challenge8 Lack of confidence and training about the rational use of antibiotics among prescribers and dispensers is a serious problem, especially when antibiotics are prescribed in the absence of cause of illness, thus increasing the risk of antibiotic resistance and adverse reactions.11 Several factors contribute to the inappropriate prescription of antibiotics, including a health care provider's knowledge and experiences, uncertain diagnosis, patient expectations, pharmaceutical marketing influences, and unregulated antibiotic dispensing.12 Additional factors, such as inappropriate antibiotic use in agriculture and food-producing animals, also pose a significant threat to human and animal drug resistance. The challenge of the latter is that there is no control of antibiotic use in agriculture and food-producing animals in Tanzania.13 To that end, there is a risk of humans acquiring resistant pathogens from food-producing animals – such risk must be examined and reduced. The consequences of irrational prescriptions of antibiotics are immense: the practice is associated with immediate economic consequences to the user4 and the overuse of antibiotics is a cause of bacterial drug resistance, which is increasingly becoming an important global public health problem.14Poor knowledge about antibiotics may be a factor influencing prescribers' attitudes toward antibiotic use and prescription practices, which then becomes a problem for patients and the community.Standard Treatment Guidelines and Essential Medicines List and other related guidelines produced by the Ministry of Health and Social Welfare.15 Studies at the local level are important to narrow the knowledge gap regarding antibiotic prescription practices among health care providers. A better understanding of physicians' knowledge, attitudes, and practices toward prescribing antibiotics is essential for formulating effective antibiotic stewardship programmes.16 Therefore, the objective of the present study was to assess knowledge, attitudes, and prescription practices related to antibiotics among health care providers in the Rombo district of northern Tanzania.Understanding the prescribing pattern of antibiotics in Tanzania is important, considering that prescriptions in the country are frequently’ based on clinical presentation of client's medical conditions. Due to an increasing number of patients and the limitations related to the nationwide availability of reliable laboratory services for all conditions, especially in hard-to-reach rural areas, health care providers tend to base their diagnoses on clinical judgment, while basing their decisions for treatment on the national 17 The Rombo district was randomly selected using the rotary method: each district name was written in a piece of paper, then 1 paper was independently selected. Systematic random sampling was employed to select prospective respondents: a starting point was chosen at random from a list of all health care providers and choices, thereafter, were made at regular intervals. The study included health care providers employed in government and non-government health facilities working in the facility for more than 1 year. We excluded providers in the internship programmes. The study was conducted among 217 health care providers from government and non-government health facilities.This descriptive study was conducted from March to June 2017, in Rombo District, Kilimanjaro, Tanzania. Kilimanjaro has 7 districts: Hai, Moshi rural, Moshi urban, Mwanga, Rombo, Same, and Siha. Rombo is bordered to the north and east by Kenya, to the west by the Hai and Siha districts, and to the south by the Moshi rural district. Within the Rombo district is a total of 43 operating health facilities, including 37 dispensaries, 4 heath centres, and 2 hospitals, and 326 health care providers.2 P(1 P)]/(d2), where Z is the value , P represents prevalence (0.846), and d is the minimum tolerable error at 95% CI, expressed as a decimal (0.05). The prevalence of antimicrobial prescription and dispensing was 84.6%.20 Therefore, N = 200 + 10% (of 200) = 220, with 10% repre senting the non-response correction.The minimum sample size was estimated using a formula expressed as N = [Z16 but adopted to Tanzania and modified for the purposes of this study. The questionnaire was validated using a small group of medical residents before it was distributed among the target population. Based on the pilot study, the questionnaire was modified and improved on advice of relevant experts in statistics and epidemiology. The final version of the questionnaire had 16 key questions subdivided into 3 categories: knowledge and attitudes, prescription practices, and accessibility and use of antibiotic therapy guidelines.Data were collected using a structured, anonymous, and self-administered 4-part questionnaire. The questionnaire content was based on a survey described in an Indian study,Briefly, part 1 recorded sociodemographic and health facility characteristics. Part 2 was composed of 8 questions on knowledge and attitudes of antibiotic prescription practices: ‘Does inappropriate antibiotic prescribing put patients at risk?’, ‘Is it always better to overprescribe antibiotics than underprescribe?’, ‘Should everyone be able to buy antibiotics without a prescription?’, ‘Is antibiotic resistance a problem in my daily practice?’, ‘Is antibiotic resistance a significant problem in my health facility?’, ‘Antibiotic resistance is a significant worldwide problem?’, ‘Are infectious diseases services at my hospital easily accessible?’, and ‘Are infectious diseases services at my health facility very helpful?’. Each question in this part was assessed using a 5-point Likert scale ranging from strongly agree to strongly disagree.Part 3 had 5 questions about prescription practice: ‘Which of these factors may influence your decision to start antibiotic therapy?’, ‘Do you ever try to make sure that your antibiotic prescribing is cost effective?’, ‘Which of these do you think are important causes of inappropriate antibiotic use?’, ‘Which of the following do you think may help control antibiotic resistance?’, and ‘Have you received regular training and education in antibiotic prescribing in your work place?’.Part 4 had 3 questions on the accessibility and use of antibiotic therapy guidelines: ‘Does your health facility provide guidelines for diagnosis and management of patient with infective problem?’, ‘How accessible are these guidelines?’, and ‘Do you follow the recommendations of your health facility antibiotic guidelines?’.Data were analysed using IBM SPSS Statistics for Windows, Version 22.0 . Data analysis was conducting using descriptive statistics, including frequencies and percentages.Permission to conduct the study was gained from the Kilimanjaro Christian Medical University College Research Ethics Review Committee and from the district medical officer. Written informed consent was obtained from all participants who voluntarily agreed to take part in this study.The response rate was 98.6%. Out of the 217 participants, 140 (64.5%) were female. A high proportion of participants  were under 30 years, followed by those between the ages of 31 and 40 years  and those over 40 years . Over two-fifths  of the participants worked at a dispensary. A majority of health care providers  were assistant nursing officers, followed by clinical officers , assistant medical officers , medical doctors , and nursing officers . Regarding years of experience, nearly a quarter  of the health care providers had more than 10 years of work experience and almost half  had between 3 and 5 years of work experience. Over half  of the participants strongly agreed and almost all of the others  agreed that inappropriate prescription of antibiotics puts patients at risk. A majority of health care providers either disagreed  or strongly disagreed  that overpre-scribing antibiotics is always better than underprescribing. More than two-fifths  disagreed that everyone should be able to buy antibiotics without prescription, and more than half  agreed that antibiotic resistance was a worldwide problem. A majority of participants agreed that infectious disease services are easily accessible  and that infectious disease services are helpful . More than half  of the health care providers reported that their decision to start antibiotic therapy was influenced by patient's clinical condition, while about half  indicated they were influenced by positive microbiological results in symptomatic patients. Almost two-fifths  responded that most of the time they try to make sure that the antibiotic prescription is cost effective. Of the important causes of inappropriate antibiotic use, poor skills and knowledge  were identified as the leading cause, followed by lack of interest in the subject of antibiotic prescribing and infection management . On important strategies to control antibiotic resistance, 119 (54.8%) were in favour of providing education to physicians on appropriate antibiotic therapy, while 70 (32.3%) suggested including knowledge of pathogens and antibiotic susceptibility results. Only 52 (24.0%) received regular training and education in antibiotic prescription in their work place  of health care providers reported that antibiotic therapy guidelines were accessible and used. About one-third  reported that the guidelines provided were comprehensive, while half  indicated that the guidelines were not always accessible when needed. Almost a quarter  of health care providers reported they never follow the recommendations of the antibiotic guidelines, while more than a quarter  reported they always follow the antibiotic guidelines –Tanzania aimed to develop policy recommendations to govern the appropriate use of antibiotics. Identified priority areas include, among others, improving hospital practices; rationalising antibiotic use in the community; educating health professionals, policymakers, and the public on sustainable antibiotic use; and ensuring political commitment to meet the threat of antibiotic resistance. However, in Tanzania, there are no current national or local data on antimicrobial surveillance. Moreover, in addition to the recommendations made by GARP, more reports are needed from the local and national levels on surveillance of antibiotic prescribing and resistance.Although this is the first report on antibiotic prescribing among providers in the Rombo district, and probably in the Kilimanjaro region, we feel that the findings are of generalized interest. This study did not interview pharmacists or patients; adding their perspectives could have provided a richer picture of prescription practices and antibiotic use. The study also did not explore the commonly used antibiotics in the study area and did not try to achieve a balance between provider location and level of practice.In this study, health care provider knowledge and prescription practices related to antibiotics were generally unsatisfactory. Our research showed that there is a clear need for training and education for health care providers in the area of antibiotic prescribing, and that antibiotic therapy guidelines should be easily accessible and effectively used.


Grin2b and Adcy5. An integrated bioinformatics analysis of regulated circRNAs identified microRNAs predicted to bind heroin-associated circRNAs and downstream targets of circRNA: microRNA sponging. Thus, heroin regulates the expression of OFC RNA splice variants that circularize and may impact cellular processes that contribute to the neurobiological adaptations that arise from chronic heroin exposure.The number of drug overdose deaths involving opioids continues to rise in the United States. Many patients with opioid use disorder (OUD) that seek treatment still experience relapse. Perseverant opioid seeking behaviors represent a major challenge to treating OUD and additional therapeutic development will require insight into opioid-induced neurobiological adaptations. In this study, we explored the regulation of a novel class of RNAs, circular RNAs (circRNAs), by the addictive opioid heroin in the rat orbitofrontal cortex (OFC), a brain region that mediates behavioral responses to rewarding stimuli. Microarray analysis identified 76 OFC circRNAs significantly regulated in male rats after heroin self-administration. We evaluated the specificity of these findings by measuring heroin-associated circRNA expression in female rats after heroin self-administration and in rats that self-administered sucrose. We identify circGrin2b, circUbe2cp, circAnks1a, circAdcy5 and circSlc24A2 as heroin-responsive circRNAs in the OFC. Linear mRNA levels of heroin-associated circRNAs were unchanged except for  Opioid overdose and deaths continue to rise in the United States, where nearly 190 people die every day from opioid intoxication ,3. HowevCircRNAs are produced from pre-mRNA via non-canonical back-splicing events, during which the 3′ donor portion of an RNA exon attacks the 5′ region of an acceptor RNA exon . This prBrain-enriched, synaptosomal circRNAs are present in the nervous system and many circRNAs are conserved from humans to rodents ,21. TherIn this study, we sought to expand upon this intriguing line of circRNA research in more detail at the molecular level in a rat model of heroin self-administration. Given that the frontal cortex has the highest abundance of circRNAs in both human and rodent brains , and is p < 0.0001; p = 0.0383) but no main effect was found for the factor time  = 1.405, p = 0.2476); however, significant interaction was found between these two factors  = 2.038, p = 0.0345). In the male saline group, no difference between the active and inactive lever was found, as expected (p = 0.0713) but a significant main effect of time was found  = 17.21, p = <0.0001) insofar as the subjects lost interest over time towards saline infusion and associated cues. Similarly, female rats self-administered more heroin than saline infusions  = 17.93, p = 0.0003, p = 0.0247), but not time  = 2.408, p = 0.1262), and a significant heroin × time interaction was detected  = 2.660, p = 0.0060 (p = 0.4619) or time  = 2.030, p = 0.1494, To identify brain circRNAs regulated by heroin exposure, we performed an unbiased circRNA expression analysis on OFC tissue from rats that underwent heroin self-administration . Male anexpected D. Two-wa= 0.0060 F. On theAt the end of the 10th self-administration session, animals were euthanized and the OFC was collected from each animal for molecular analyses of circRNA expression as described in Grin2b) gene appeared in four of the enriched terms. As we further explored the identity of genes that are spliced following heroin self-administration, we observed significant dysregulation of multiple circRNAs derived from the same gene. Five circRNAs from ankyrin repeat and sterile alpha motif domain containing 1B (Anks1b) were regulated by heroin; three from Grin2b and ubiquitin protein ligase E3D (Ube2cbp/Ube3d); and two each from exocyst complex component 6 (Exoc6), membrane associated guanylate kinase, WW and PDZ domain containing 2 (Magi2), mitogen-activated protein kinase kinase kinase kinase 5 (Map4k5), reticulon 4 (Rtn4) and solute carrier family 24 member 2 (Slc24a2), indicating that these genes may undergo additional splicing events , rno_circRNA_004685 (Cnot6l), rno_circRNA_009909 , rno_circRNA_012370 (Slc24a2), rno_circRNA_004644 (Rtn4), rno_circRNA_012514 , rno_circRNA_003235 , rno_circRNA_016706 (Ube2cbp), rno_circRNA_001230 , and mmu_circRNA_39652 . We selected circRNAs that were derived from genes highlighted in the gene ontology and pathway analyses  = 3.307, p = 0.002; circAnks1a, t (38) = 2.070, p = 0.045; circUbe2cbp, t (37) = 2.718, p = 0.010)  = 2.433, p = 0.026; circSlc24a2, t (20) = 2.175, p = 0.042; circAdcy5, t (23) = 3.258, p = 0.035; circUbe2cbp, t (23) = 2.453, p = 0.022; p = 0.053). Overall, the regulation of five putative heroin-associated circRNAs  = 3.476, p = 0.001; circAnks1a: t (58) = 2.981, p = 0.004; circSlc24a2: t (44) = 2.320, p = 0.025; circAdcy5: t (63) = 2.654, p = 0.010; circUbe2cbp: t (62) = 2.975, p = 0.004). We further validated the existence of each circRNA by performing an RNase R digestion assay followed by qPCR for circRNA and linear mRNA pairs. circRNAs are resistant to RNase R digestion while typically many mRNAs, but not all, are rapidly degraded by RNase R treatment [To examine the accuracy of the microarray findings and the reproducibility of heroin-induced circRNA regulation, we measured expression of 10 heroin-associated circRNAs in biological replicate male and female animals after heroin self-administration using qPCR. We designed TaqMan probes that span circRNA back-splice junctions (BSJs) of 10 circRNAs: rno_circRNA_011731  A. No stacircRNAs C identifreatment . As expeGrin2b was significantly elevated after heroin in the same direction of its circular transcript, rno_circRNA_011731 (unpaired t-test: t (25) = 2.407, p = 0.024, Anks1a, Slc24a2, Adcy5 and Ube2cbp was not significantly different between male heroin and saline animals. In female animals, linear Grin2b, Anks1a, Slc24a2 and Ube2cbp were not regulated by heroin, but linear Adcy5 was significantly elevated (unpaired t-test: t (24) = 2.515, p = 0.019; Individual circRNAs may be co-regulated with their linear counterparts or independently regulated , suggestp < 0.0001; female sucrose: F  = 128.60, p < 0.0001; t-test: t (26) = 2.209, p = 0.036; To investigate whether the OFC circRNA expression changes detected in the heroin-exposed rats were specific for a drug reward or may generalize to an unspecific physiological response to a rewarding stimulus, we evaluated the expression level of heroin-associated circRNAs in a separate cohort of rats that underwent sucrose self-administration . Male anBax , Egr1 (early growth response 1), Elk1 (ETS transcription factor ELK1), Mapk3 (Erk1) (mitogen-activated protein kinase 3) and Ncam1  [Many circRNAs contain miRNA recognition elements (MREs) that may function to limit the role of a miRNA within a cell . miRNAs ecule 1) ,46,47,48circRNAs represent a novel species of RNA to study in models of addiction. Although circRNAs were discovered decades ago, limited exploration into the relationship between circRNAs and drug abuse has been completed thus far. While other studies in the neuroscience field have demonstrated that circRNAs can modulate neuronal function ,22, the In this study, we have identified a set of heroin-associated circRNAs consistently regulated by heroin self-administration in the OFC of adult rats. circGrin2b, circSlc24a2, circAdcy5, circAnks1 and circUbe2cbp were all identified with an unbiased microarray analysis of the circRNA profile altered by chronic heroin self-administration in male rats. We subsequently validated these results using qPCR in male and female rats to ensure reproducibility of the data. We did not detect any sex by treatment interactions when examining the expression of these putative heroin-associated circRNAs and do not conclude that regulation of the five validated circRNAs are sex-specific. Further analysis is required to examine sex-specific regulation of circRNAs after heroin exposure and accurate detection of some circRNA changes may require large sample sizes due to small effect sizes. Grin2b in male animals and upregulation of Adcy5 in female animals. The upregulation of circGrin2b and circAdcy5 in these respective groups of animals may therefore be due to more copies of the linear isoforms of Grin2b and Adcy5 being produced in response to heroin. In contrast, upregulation of circAnks1a, circSlc24a2 and circUbe2cbp was not accompanied by a change in linear mRNA levels and may be due to heroin-induced modulation of a splicing factor. Drug-induced regulation of splicing factors has been previously reported [At the level of linear mRNA expression, we only detected significant upregulation of reported ,50.Overall, our analysis suggested that the changes in circRNA expression detected in the heroin-exposed rats tends to be highly specific. Out of the five heroin-associated circRNAs that were validated, only one was dually regulated by sucrose self-administration, circUbe2cbp. The overlapping regulation of circUbe2cbp suggests that this circRNA may function as a more general response to any rewarding stimuli, including palatable food rewards. In contrast, the other four circRNAs—circGrin2b, circSlc24a2, circAdcy5 and circAnks1a—were not regulated by sucrose and appear to be specific for heroin reward. Whether any of these five circRNAs are also regulated in the OFC by other drug rewards, such as alcohol or cocaine, has not yet been determined as no such study has been performed, but circUbe2cbp seems the most likely candidate for regulation by multiple rewarding stimuli. We demonstrated that heroin self-administration of a 0.03 mg/kg dosage can induce regulation of 76 circRNAs in the OFC. This dosage of heroin has been used by many labs to model drug-seeking behavior and we have previously demonstrated that animals that have higher amounts of drug intake at this dosage typically have more drug-seeking behavior after extended forced abstinence . HoweverBax, Egr1, Elk1, Mapk3 (Erk1) and Ncam1. Specifically in the context of opioids, abstinence from heroin self-administration upregulates Egr1 in the frontal cortex of rats [Mapk3 (Erk1) has also been reported to be upregulated in the locus coeruleus and striatum of rats treated with morphine [Elk1 has been reported in the nucleus accumbens of rats that self-administered the same heroin dosage used in this study as well as in postmortem tissue from patients with heroin use disorder [Interrogation of the putative microRNA pathways that may be affected by heroin-associated circRNAs revealed a list of microRNAs largely unstudied in the field of addiction neuroscience. We identified 26 microRNAs that are predicted to bind at least three heroin-associated circRNAs and an additional 12 microRNAs predicted to bind circGrin2b, circAdcy5, circAnks1a, circSlc24a2 or circUbe2cbp. Of these, let-7b-5p, which is predicted to bind circAdcy5, has been reported to be elevated in both the serum and the plasma of patients with heroin-use disorder ,53. More of rats . Levels morphine ,46. ReguOur study of circRNAs regulated by heroin in the OFC is the first unbiased analysis of heroin-induced circRNA expression published to date. Microarrays represent a suitable method of circRNA measurement but are not without limitations. The probes that are used in the microarray are only designed to detect the backsplice junction of a circRNA. Because of this, no information is available regarding the true size of the circRNA detected. Many circRNAs can arise from one linear RNA and various combinations of exons or introns may be included. We have listed the genomic size of the circRNAs detected in the microarray performed here as well as the predicted size of the validated heroin-associated circRNAs including only exons that exist between the genomic coordinates. An exception to this is circSlc24a2, which contains a backsplice junction that includes an intron. Previous studies have indicated that the majority of circRNAs only contain exons and our data describing the location of the backsplice junction in The existing literature on drug-induced circRNA expression has reported circRNA regulation in primary cortical neurons and the cerebellum in response to methamphetamine treatment, and in the striatum in response to cocaine self-administration ,55,56. NSeventy-seven adult male and fifty-six adult female Sprague Dawley rats (Charles River Laboratories), 8 weeks old, were used in this study. Animals were pair-housed on a reverse light/dark cycle  with constant room temperature (22 ± 2 °C) and humidity (40%). Animals were provided food ad libitum except where described. All procedures followed the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals and were approved by Temple University’s Institutional Animal Care and Use Committee.Diamorphine hydrochloride (heroin) was obtained from the National Institute on Drug Abuse drug supply program and dissolved in 0.9% sterile sodium chloride for drug self-administration experiments.After 5–7 days of acclimation, animals underwent intravenous catheter surgery for heroin or saline self-administration, as previously described . FollowiHeroin self-administration studies were conducted in operant chambers under a fixed ratio (FR) 1 schedule, as previously described . For herImmediately after the 10th self-administration session, all animals were briefly anesthetized with 5% isoflurane and rapidly decapitated. Brains were removed and frozen in ice-cold isopentane on dry ice. Brains were kept at −80 °C until dissection. The orbitofrontal cortex (OFC) was dissected with a 1mm sample corer on a cold plate maintained at −20 °C to ensure tissue remained frozen. Frozen tissue punches were stored at −80 °C until RNA extraction. Total RNA was extracted from OFC tissue using the MIRvana Paris Protein & RNA Isolation System  according to manufacturer’s instructions as previously described . The RNAt-test. circRNAs having fold changes >1.5 and p-values < 0.05 were selected as significantly differentially expressed. A proprietary algorithm owned by Arraystar was used to predict miRNA:circRNA interactions. All raw microarray data have been deposited to the Gene Expression Omnibus repository under record GSE189192 and descriptive statistics of microarray data can be found in Detection of differentially expressed circRNAs was achieved with microarray analyses performed by Arraystar Inc. . A total of 2.5 μg of pure RNA from 8 individual male OFC samples was submitted for analysis. Purity and concentration of total RNA samples were determined using a NanoDrop ND-1000 . RNA integrity was assessed by electrophoresis on a denaturing agarose gel. Sample labeling and array hybridization were performed according to the manufacturer’s protocol . Briefly, total RNAs were digested with RNase R  to remove linear RNAs and enrich circular RNAs. Then, the enriched circular RNAs were amplified and transcribed into fluorescent cRNA utilizing a random priming method . The labeled cRNAs were purified by RNeasy Mini Kit (Qiagen). The concentration and specific activity of the labeled cRNAs (pmol Cy3/μg cRNA) were measured by NanoDrop ND-1000. A total of 1 μg of each labeled cRNA was fragmented by adding 5 μL 10 × Blocking Agent and 1 μL of 25 × Fragmentation Buffer, then heated the mixture at 60 °C for 30 min, and finally 25 μL 2 × Hybridization buffer was added to dilute the labeled cRNA. In total, 50 μL of hybridization solution was dispensed into the gasket slide and assembled to the circRNA expression microarray slide. The slides were incubated for 17 h at 65 °C in an Agilent Hybridization Oven. The hybridized arrays were washed, fixed and scanned using the Agilent Scanner G2505C. Scanned images were imported into Agilent Feature Extraction software for raw data extraction. Quantile normalization of raw data and subsequent data processing were performed using the R software limma package. After quantile normalization of the raw data, low intensity filtering was performed, and the circRNAs that had at least 3 out of 12 samples ‘present’ were retained for further analyses. Statistical significance was estimated by Gapdh) were use as endogenous controls. Expression levels were calculated using the 2−ΔΔCt method [qPCR measurement of differentially regulated circRNAs or their linear counterparts was performed using a Quantstudio3 qPCR machine . A total of 500 ng of total RNA was reverse transcribed into cDNA using 200 units of Maxima Reverse Transcriptase , 20 units of RiboLock RNase inhibitor , 0.5 μM dNTP mix , 100 pmol random hexamer primers  and 4 μL 5X RT Maxima RT buffer . Reverse transcriptase reactions were incubated at 25 °C for 10 min, 50 °C for 30 min and inactivated at 85 °C for 5 min. cDNA was diluted 1:10 then used as a template in qPCR reactions with IDT PrimeTime Gene Expression Mastermix and IDT PrimeTime qPCR Probe Assays . Beta actin and glyceraldehyde 3-phosphate dehydrogenase (t method . A full 2 and 1 M LiCl), 1 μL of Ribolock RNase inhibitor, and 3U of RNase R enzyme. Following RNase R digestion, reactions were immediately reverse transcribed for qPCR as described above.Poly(A) tailing followed by RNase R digestion was performed as described  with minp-value of less than 0.05. Pathway analysis of predicted miRNA targets was performed using DIANA mirPath v3 software [p value of less than 0.001.Gene ontology pathway analyses were performed on the list of linear mRNA genes from which heroin-associated circRNAs are derived, using the DAVID Bioinformatics Database v6.8 developed by the Laboratory of Human Retrovirology and Immunoinformatics at NIH ,63. Analsoftware . A ‘patht-tests were used to analyze differences between two groups with normal distributions. Nonparametric Mann–Whitney tests were performed to compare differences between two groups without a normal distribution. A p-value of less than 0.05 (p < 0.05) was considered statistically significant. Statistical analyses of qPCR data were performed on ΔΔCT values prior to log transformation of fold change. GraphPad software was used for all analyses .Mean data are presented, with error bars indicating the standard error of the mean (SEM). Two-way analysis of variance (ANOVA) with repeated measures (RM) was performed on self-administration infusion data by using heroin or saline availability as the between-subject factors and time as within-subject factor. Two-way RM ANOVA was used to compare self-administration of the active versus inactive lever over 10 days. D’Agostino normality tests were performed on all datasets. Unpaired Student’s


No differences were seen between preoperative or both pre- and postoperative antibiotic regimens . A single preoperative antibiotic prophylaxis dose was found to be enough to significantly reduce early implant failures compared to no antibiotic . In conclusion, in healthy patients a single antibiotic prophylaxis dose is indicated to prevent early implant failure.Systemic antibiotics are routinely prescribed in implant procedures, but the lack of consensus causes large differences between clinicians regarding antibiotic prophylaxis regimens. The objectives of this systematic review are to assess the need to prescribe antibiotics to prevent early implant failure and find the most appropriate antibiotic prophylaxis regimen. The electronic search was conducted in PubMed/MEDLINE, Scielo and Cochrane Central Trials Database for randomized clinical trials of at least 3 months of follow-up. Eleven studies were included in the qualitative analysis. Antibiotics were found to statistically significantly reduce early implant failures (RR = 0.30, 95% CI: 0.19–0.47,  The failure of dental implants according to chronological criteria can be divided into early failure, when it occurs before or during the abutment connection, or late failure, after prosthetic loading . Early iDue to the diversity of the microbiota present in the oral cavity, the second most diverse and large on the human body , systemiRandomized clinical trials (RCTs) on this topic show different conclusions: that antibiotic prescription may not be necessary in case of proper asepsis  or in siRegarding the type of administration, most of the studies suggest that a single preoperative dose of antibiotic is enough to prevent the early implant failure, thus avoiding long-term antibiotic administration ,17,18,19The type of antibiotic is the only aspect in which there seems to be a consensus, amoxicillin being the most widely prescribed antibiotic in implant dentistry followed by amoxicillin in association with clavulanic acid ,10. LikeDue to this lack of consensus and with the aim of shedding light on this issue, the objectives of this systematic review are to assess the need for systemic antibiotics in patients undergoing dental implant placement to prevent early implant failures and to find the most appropriate antibiotic prophylaxis regimen in these procedures considering its efficacy and the prescribed dose.The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement . A detaiDoes the administration of antibiotic prophylaxis reduce early implant failure?If the answer is yes, what is the best antibiotic prophylaxis regimen to reduce early implant loss?P (population): Partial or totally edentulous patients undergoing dental implant surgery.I (intervention): Administration of any type of systemic antibiotic, regardless of dosage, duration or time of administration.C (comparation): Different type of antibiotic, dosage, duration or time of administration, or compared to placebo or no antibiotic.O (outcome): Early implant failure .Randomized Clinical Trials.At least 3 months follow-up.Antibiotic prophylaxis regimen clearly described.Partial or totally edentulous patients undergoing dental implant surgery.Inclusion criteria:Local antibiotic application instead of systemic antibiotic prophylaxis.Patients requiring antibiotic prophylaxis for medical reasons.Exclusion criteria:An electronic search of the literature was conducted by two authors (E.R.-M. and A.E.-D.) for articles written in English or Spanish published from January 2000 to April 2021. The consulted databases were PubMed/MEDLINE, Scielo and Cochrane Central Trials Database. An additional hand search was performed to identify studies with potential of inclusion in the references of the articles identified in the electronic search. Both searches were conducted on 9 April 2021. The following term combination was used in all databases:  AND .The study selection was carried out by two authors (E.R.-M. and A.E.-D.). After discarding duplicate articles, the titles were read to identify studies with potential for inclusion. Then, the abstracts were read to discard papers that did not meet the inclusion/exclusion criteria. Full text of the selected articles was read to verify that they met the inclusion/exclusion criteria. Disagreements between the two authors were solved consulting a third author (J.L.-L.).The data were independently extracted by two authors (E.R.-M. and A.M.) and entered in data collection forms (Microsoft Excel version 16.35). In case of disagreement a third author was consulted (J.L.-L.). The collected data included author(s), year of publication, country, type and number of centers, follow-up period, number of patients and implants analyzed, inclusion and exclusion criteria, aseptic measures before and after surgery and type of antibiotic, dosage, duration and time of administration of the different test and control groups. Corresponding authors were contacted in the event that data were missing.Version 2 of the Cochrane Collaboration’s tool for assessing risk of bias in randomized clinical trials (RoB 2)  was implA qualitative analysis of the included articles was be carried out by grouping those according to the characteristics of the test and control groups.2 ≥ 40%). Review Manager (RevMan)  was implemented to calculate the Risk Ratio (RR) and 95% confidence interval. The level of significance was set at p < 0.05 and heterogeneity was evaluated with Chi2 and I2 tests. The statistical unit was the dental implant.For the quantitative analysis, pooled estimates from the studies were performed using a fixed or random effect-model depending on the heterogeneity  ,27,28,29Most studies had a preoperative antibiotic prophylaxis group  ,26,27,28In cases in which a single dose antibiotic prophylaxis was prescribed, the most frequent dose was 2 g amoxicillin 1 h before the surgery. Although in one study 1 g amoxicillin was administered  and in aIn cases in which only postoperative antibiotic was administered, the duration of the treatment was 7 days ,29. WhenRegarding hygienic and aseptic measures, in five of the studies patients received prophylaxis, debridement and/or oral hygiene instructions when required a few days before implant surgery ,27,28,29Regarding the complexity, two studies specified that the surgical procedures involved only the placement of simple single dental implants ,29. DataFour of the included RCT obtained a low overall risk of bias ,18,27,28Of the eight studies that compared the administration of antibiotic prophylaxis with no antibiotic or with placebo ,27,28,29Four RCT compared preoperative antibiotic regimen with both pre- and postoperative antibiotic regimen, and in none of the cases were statistically significant differences found ,18,19,26The implant failure rate in the antibiotic groups was 1.55%, while in the no antibiotic or placebo groups was 4.61%.2 < 40%. The prescription of antibiotic prophylaxis, regardless of the dosage or the time of administration, proved to be a protective factor for early implant failure, with statistically significant results  [Different pooled estimates were performed using a fixed effect-model because heterogeneity was I = 0.54) ,27,28,29p = 0.27; heterogeneity I2 = 0%, p = 0.37) [The meta-analysis comparing preoperative antibiotics versus pre- and postoperative antibiotics did not show differences between groups  ,18,19,26 = 0.37) ,19  [A single preoperative antibiotic dose compared with no antibiotic prescription, turned out to be a significant protective factor in early implant failure  ,26,27,28According to the results obtained in the present systematic review and meta-analysis, antibiotic prophylaxis is indicated in dental implant procedures since they statistically significantly reduce early implant failure. No difference has been observed between the administration of a single preoperative antibiotic dose and the combination of pre- and postoperative antibiotics. A single preoperative dose has been found to be enough to significantly reduce dental implant failures compared to no antibiotic or placebo.Even so, the most recent cross-sectional studies reveal an antibiotic over prescription in relation to this type of surgical procedures, being very common in some countries, such as Spain and Italy, the prescription of antibiotic from one or two days before implant placement to five or seven days after surgery ,10.The results obtained agree with those found in recent systematic reviews and meta-analyzes ,31,32,33It should be taken into account that the included RCTs treated patients without systemic conditions that could pose a greater risk of implant failure, so if the protective effect of the antibiotic is observed in healthy patients, its use is indisputable in patients at risk.All the studies that focused on the effect of antibiotic regimens in early implant failure used amoxicillin as the antibiotic of choice or, in case of allergy, clindamycin. However, it appears that bacteria genes encoding resistance to metronidazole are less frequent in peri-implant tissues than those that encode resistance to beta-lactams . In addiOn the other hand, local antibacterial drug delivery systems are being investigated in the field of oral implantology, which would allow to maintain the minimum inhibitory concentration of antibiotic around dental implants during the osseointegration time ,41.Although the mechanisms of antibiotic therapy in implant dentistry could change a lot in the coming decades, due to the large number of dental implants placed each year and therefore the large number of patients undergoing antibiotic prophylaxis, it is essential to establish antibiotic protocols both for patients at risk and for healthy patients. It would also be interesting to differentiate between simple and complex implant procedures.The limitations of the present study are the small sample and the unclear risk of bias especially regarding the blinding of participants and researchers in some of the included studies, the low number of RCTs with a follow-up period of at least 3 months that analyze this question and the lack of studies comparing different doses of preoperative amoxicillin prophylaxis.Systemic antibiotic prophylaxis significantly reduces early dental implant failures in healthy patients. There is no statistically significant difference in the occurrence of this event when comparing the pre and postoperative administration of systemic antibiotics with the prescription of a single preoperative antibiotic dose. Therefore, the continuation of antibiotic treatment postoperatively would not be indicated in these patients.Future research should be aimed at establishing differences between the systemic antibiotic needs of healthy patients versus patients with systemic diseases, of patients with or without different types of oral diseases or comparing simple implant surgeries versus complex procedures. In addition, RCTs comparing different single preoperative antibiotic doses should be performed.


In this study, basalt, which is common around Diyarbakır province (Turkey), is used as concrete aggregate, waste materials as mineral additives and Portland cement as binding material to prepare concrete mixes. This paper aims to determine the proper admixture levels and usability of Diyarbakır basalt in concrete mixtures based on mechanical, physical and chemical tests. Thus, in order to determine the strength and durability performance of concrete mixtures with Diyarbakır basalt as aggregate, 72 sample cubes of 150 mm were prepared in three groups: mineral-free admixture (MFA), 10% of cement amount substituted for silica fume (SFS) and 20% for fly ash (FAS) as waste material. The samples were exposed to water curing and 100g/L sulphate solution to determine the loss in weight of the concrete cubes and compressive strength was examined at the end of 7, 28 and 360 days of the specimens. Analysis of the microstructure and cracks that influence durability, were also performed to determine effects of sulphate attacks alkali-silica reactions on the specimens using scanning electron microscopy (SEM). A loss in weight of the concrete cubes and compressive strength was distinctly evident at the end of 56 and 90 days in both acids. Approximately 70–75% of concrete volume is composed of aggregates. Among the commonly preferred concrete aggregates are limestone and dolomite. However, given that concrete is the most commonly used building material the world over, it is often necessary to make use of alternative rocks . Basalt Some studies were done on basalt aggregate concretes in the middle of 20th century, the results of which revealed that basalt rocks were superior compared to other rocks. The thermal expansion coefficient, conduction and conduction velocity of basalt are low. Neither temperature rises nor crack formation was observed during the cooling ,5,6. DurBasalt is formed mainly from feldspar under the natural stones classification and is dark grey and black in color in the nature, being a stiff and durable volcanic rock. It is commonly found in various properties in Diyarbakır province and its neighborhood, the East and Central Anatolia and Thrace regions in Turkey ,11. Basa2 particles has been widely used to produce high strength concrete. SF as a highly pozzolanic material that can participate in the pozzolanic reactions occurring during the very early stages of cement hydration. In addition, because it has very small particles, SF could also act as a filler in the pores and voids in concrete to improve the permeability. Moreover, SF particles contribute to the precipitation of hydration products that accelerate cement hydration leading to hardened concrete with a refined pore structure [Supplementary cementitious materials (SCMs) can reduce the amount of cement in cementitious mixes without significantly changing their mechanical properties. Silica fume (SF), comprised primarily of microscale size SiOtructure ,13,14. Otructure ,16,17. Mtructure .2 amount and total of Na2O + K2O alkaline do not exceed 45–52% and 5% respectively according to the systematic of igneous rocks basic features and that its use in concrete does not lead to ASR [The International Union of Geological Sciences (IUGS) has reported that the rock whose SiOd to ASR . In acced to ASR .In this paper, to heighten the strength and durability of concrete, Diyarbakır Karacadağ crushed basalt and waste mineral admixtures , by-products of various industries which resemble cement, were used as concrete aggregate. Proper admixture levels in concrete mix were tested to determine the mechanical, physical and chemical properties for various conditions. Moreover, the effects of hazardous environments such as sulphate attacks on the specimens discussed. This paper is prominent as it aims to determine and usability of Diyarbakır basalt as an alternative aggregate material obtained from the Tigris river stream bed. Utilization of Diyarbakir basalt in concrete industry will not only avoid the use of aggregates obtained from streamside and thereby avert degradation of stream beds but also will allow reclamation of lands from which the basalt is removed to provide farmland.2 in Southeast Anatolia, Turkey and occur approximately a half meter below the soil cover or as a surface cover. The creeping basalt flow from Karacadağ volcano that formed these basalt rocks is common, most notably in the Diyarbakır wide basalt plateaus that are found across 120 to 130 km.Diyarbakır and Karacadağ mountain basalt, found locally in deposits as thick as 150 m cover an area of 10,000 km3 in the west, 2.91–2.93 g/cm3 in the north and 2.45–2.47 g/cm3 in the east, respectively. Mean uniaxial strength of Diyarbakır basalt rock (five samples) with a diameter of 42 mm and height of 102 mm is 51.76 MPa for the porous form and 89.10 MPa for the non-porous one [Diyarbakir Karacadağ basalt rock is usually dark grey or black in colour. Some other basalt rocks may weather to lighter colours. They may also weather to a brown colour following oxidation of ferrous minerals . Diyarbarous one . A comparous one .Other properties of Diyarbakır-Karacadağ basalt such as high abrasion strength, low thermal conductivity and acid and frost resistance have diversified the areas of its use and led to an increase in the number of studies related to the material being performed nowadays. Kahveci and Kadayifçi  have rep2 in aggregates used in concrete admixtures leading to a reaction with Na2O and K2O  components that form the cement [Alkali silica reaction (ASR) is a form of concrete degradation occurring as a result of available reactive SiOe cement . ASR-base cement . Reactioe cement :H0.38 SiThe product of alkali silica reaction is a highly hydrophilic alkali silica gel . As alka2 content is less than 51% [2O amount is 0.50% as low alkali and cements with 1.04% amount as high alkali. Where highly reactive rocks to ASR and low alkali cements are used, the ASR impact has been identified to be reduced. Chemical analysis of the cement applied during the test is given in Considering the chemical data in than 51% ,32. The It was observed that ASR products generally are located in voids, in-between cracks of aggregates and aggregate-cement paste. Having different morphological structures, massive ASR products can be clearly seen in 2 content cause cracks that create a volumetric expansion due to alkali-silica reactions, as shown in The effects of alkali-silica reactions were investigated by scanning electron microscopy (SEM) for mortar samples of granite aggregates and CEM I 42.5R Portland cement . AccordiThe alkali silica reaction (ASR) effects on mortars containing various proportions of silica fume (SF) and fly ash (FA) as replacement of cement were investigated with respect to the ASTM C 1260-07 standards . It is nIn this paper, as admixture materials fly ash (FA) from the Kahramanmaraş Afşin Elbistan Thermal Reactor , was taken. Silica fume (SF) was from the İstanbul Aryum Company  and cement from the Limak Ergani Cement Plant  of Portland 42.5 cement category that is similar to ASTM C type have been utilized, as tabulated in Analysis results of mineral admixtures were conducted at the Limak Ergani Cement Plant. Determinations of specific surface area of the materials were made via a Blaine test using Blaine test equipment in compliance with TS EN 196:6, ASTM C 204 standards, and an approximate value of the specific surface area of silica fume was obtained using the nitrogen adsorption method. Physical and chemical analysis results of the materials applied during the test are shown comparatively in 2 + Al2O3 + Fe2O3 is more than 70. Class F fly ashes are pozzolanic and do show binding properties on their own. Silica fume, used in concrete as admixture, has a SiO2 content of more than 85%. Oxides like Al2O3, SO3, MgO, Na2O and K2O are found in amounts of less than 1% [ than 1% . On the The sieve analysis according to TS 1225 shown in The concrete samples were prepared in 72 cubes of 150 mm divided into three groups in which mineral free admixture (MFA) was available and 10% of cement amount was substituted for silica fume (SFS) and 20% for fly ash (FAS). The specimens were exposed to 100g/L sulphate solution and crushed at the end of days 7, 28 and 360 to determine hydropathy and durability. According to ASTMC1012, 50g/L magnesium sulphate solution used. However, in the previous study it was observed that the relevant solution failed to exhibit differences in relation to sulphate durability of prepared admixtures .3 was used as chemical admixture. In modified concretes, cement was replaced by admixtures FA and FS by their weight, the content of 1 m3 concrete values are given in Fifteen cm cubic concrete samples prepared for the test were designed in compliance with TS 802 (2009) standards and C30 concrete class. A superplasticizer whose specific weight was 1.15 g/cmAccording to the classification of samples calculated with the slump amounts via slump test provided in TS EN 201-1 given in 2/sec. Comparative compression values are given in The three test groups were constituted with the replacement percentages of 0% (the plain concrete-MFA), 10% (SFS-10) and 20% (SFA-20) specimens were cured for 7, 28 and 360 days under laboratory conditions. Concrete compressive strength values, mean value and strength were calculated by crushing three samples, each of which had different designs, through pressure tests run with a hydraulic system on which the load applied was set at 0.6 N/mmRegarding the variation of the strength rates between hydropathy and sulphate solution considered for the short term (7-days) MFA did not affect these parameters, but the FAS samples were very affected, showing about a 21% decrease in strength. On the other hand, comparing the compression strength values for days 7, 28 and 360 within hydropathy and sulphate solution, silica fume substitute concrete specimens demonstrated the highest performance. Whereas fly ash substitute concrete demonstrated the lowest strength at an early age, it approached the free admixture concrete strength value by day 28, and its strength value at an advanced age measured on day 360 turned out to be higher than that of a admixture-free concrete. The change in compression strength values of concrete samples soaked in hydropathy and sulphate solution on day 360 and day 28 are given in percentages in The mass loss ratios of samples kept in water and sulphate solution for 7, 28 and 360 days are given in As stated in 2 content cured in sulphate solution and hydropath for 90 days are shown in In order to investigate effects of mineral admixtures on the microstructure of various concrete bar samples of plain concrete and mineral additive replacement of CEM I 42.5 Portland cement observations by scanning electronic microscopy (SEM) were performed The various bar specimens of Diyarbakır basalt aggregates with %50 SİOThe effects of alkali-silica reactions were observed by SEM in the hydropath samples after curing for 90 days, as shown in For the samples cured for 90 days in sulphate solution, the effects of alkali-silica reactions were observed by SEM as shown in In the SEM images shown in Utilization of Diyarbakir basalt in the concrete industry as a locally available raw material with high strength capacity will not only prevent the use of aggregates obtained from riversides, and thereby avert the degradation of river beds, but also will allow reclamation of lands from which the basalt is mined to provide farmland. On the other hand, the use of waste minerals such as fly ash with appropriate proportions of cement replacement in concrete mix saves both the energy consumed for cement production and carbon emissions, addressing an important environmental issue.The compression strength results of 28-day-old concrete with basalt aggregates (43–50 MPa) indicate that samples designed as C30 (30 MPa) class exhibit much better performance than those expected with respect to the standards for both hydropathy and sulphate solution curing conditions.Silica fume substitute concrete specimens achieved the highest compression strength both in hydropathy and sulphate solution at the early and long-term stages.The most economical specimens of fly ash as partial replacement of cement in concrete mix performed close to the 28-day compressive strength of the plain concrete samples.In the long-term case the FA replacement specimens provided improvements in strength for both in hydropathy and sulphate solution.In the short-term case the FA replacement specimens present weak behaviour in strength and mass loss cases for both curing conditions.In all cases of short and long-term  under both curing conditions the cement-replaced admixtures (10% SFS and 20% FA) of concrete specimens provided lower concrete mass lossesf.Large cracks were observed in the MFA (plain concrete) and SFS (10% silica fume substituted) samples that were exposed to the sulphate solution for 90 days.In the SEM observations of the 20% FA substituted samples exposed to sulphate solution only capillary cracks were observed which represents an improvement in crack formation.It is clearly noted that the sulphate-resistant samples containing fly ash perform much better than the other samples in terms of durability and concrete strength over long-term periods.As it is noted the samples produced with Diyarbakır basalt aggregate did not show any volumetric cracks after 90 days of curing and were not reactive to ASR as the microstructure seen in SEM images did not change and products related to alkali-silica reaction were not observed. The chemical analyses of all five samples revealed that there is no objection in terms of ASR for the use of Diyarbakir basalt as concrete aggregate. Additionally, the mineral admixtures such as FA can improve the microstructure as well as the compressive strength reducing the mass loss of concrete. The following conclusions are derived to summarise our results in view of the results and discussion presented in this research work: