Bevacizumab improves survival outcomes in women diagnosed with epithelial ovarian cancer (EOC). Pre-clinical data showed that the c-MET/VEGFR-2 heterocomplex negates VEGF inhibition through activation of c-MET signalling, leading to a more invasive and metastatic phenotype. We evaluated the clinical significance of c-MET and VEGFR-2 co-localisation and its association with VEGF pathway-related single nucleotide polymorphisms (SNPs) in women participating in the phase 3 trial, ICON7 .VEGFA and VEGFR-2 SNPs was performed. The significance of these biomarkers was assessed against survival.Patients had FIGO stage I-IIA grade 3/poorly differentiated or clear cell carcinoma or stage IIB-IV epithelial ovarian, primary peritoneal or fallopian tube cancer. Immunofluorescence staining for co-localised c-MET and VEGFR-2 on tissue microarrays and genotyping of germline DNA from peripheral blood leukocytes for HIGH group treated with bevacizumab demonstrated significantly reduced OS . Germline DNA from 449 women underwent genotyping. In the bevacizumab group, those women with the VEGFR-2 rs2305945 G/G variant had a trend towards shorter PFS compared with G/T or T/T variants .Tissue microarrays from 178 women underwent immunofluorescence staining. Multivariable analysis showed that greater c-MET/VEGFR-2 co-localisation predicted worse OS in patients treated with bevacizumab after adjusting for FIGO stage and debulking surgery outcome . Women in the c-MET/VEGFR-2VEGFR-2 rs2305945 G/G variant, which may be biologically related, were associated with worse survival outcomes.In bevacizumab-treated women diagnosed with EOC, high c-MET/VEGFR-2 co-localisation on tumour tissue and the The online version contains supplementary material available at 10.1186/s12916-022-02270-y. Tissue microarrays and germline DNA from women recruited to the phase 3 trial, ICON7, underwent quantitative immunofluorescence for c-MET/VEGFR-2 co-expression and genetic sequencing for single nucleotide polymorphisms (SNPs) VEGF-pathway genes.High c-MET/VEGFR-2 co-localisation on tumour tissue independently predicted worse survival in bevacizumab-treated epithelial ovarian cancer.VEGFR-2 rs2305945 SNPs also independently predict worse survival in bevacizumab-treated epithelial ovarian cancer.The The online version contains supplementary material available at 10.1186/s12916-022-02270-y. Ovarian cancer is the commonest cause of gynaecological cancer-related death in Europe and North America . Multi-mIn our initial study of pre-treatment biomarkers, a group of patients were identified who appeared to be disadvantaged by bevacizumab , 9. The All participants provided written informed consent for the International Collaboration of Ovarian Neoplasms 7 (ICON7) trial : an international, randomised, multi-centre, open-label, phase 3 trial investigating the use of bevacizumab maintenance therapy as part of the first-line therapy in women diagnosed with high-risk FIGO (1988) stage I–IIA (grade 3/poorly differentiated tumours or clear cell carcinoma) or FIGO (1988) IIB-IV epithelial ovarian, primary peritoneal or fallopian tube cancer . ProgresTissue microarrays (TMAs) from EOC tumour tissue sections underwent immunofluorescent staining using the BenchMark ULTRA system according to the RUO DISCOVERY universal staining procedure . TMA sections were deparaffinised at 69°C for 8 min per cycle. Antigen retrieval occurred by pre-treatment with Cell Conditioning Solution 2 (CC2)  and incubation at 95 °C for 4, 8, 16, 24 and 32 min. TMA sections were then blocked by incubating with DISCOVERY inhibitor  for 8 min. Sections were warmed to 37 °C and then incubated with the following primary antibodies: VEGF receptor 2 (55B11) rabbit monoclonal antibody  and c-MET (1G7NB) mouse monoclonal antibody  for 60 min. Sections were then incubated with the corresponding HRP-conjugated secondary antibodies for 8 min. The Tyramide Signal Amplification (PerkinElmer) was used on all slides to improve visualisation following incubation with the secondary antibody. Tyramide labelled with Cy3  or FITC  diluted in 1X Plus Amplification Diluent (PerkinElmer) were used.Following the first staining, the second staining on the same section was performed using anti-human collagen type IV  to identify the stroma in each core. Sections were pre-treated with CC2 at 95 °C for 4 min and then 8 min. Slides were then cooled to 37 °C before the second primary antibody was applied manually, followed by incubation for 60 min. Slides were then incubated with a corresponding HRP-conjugated secondary antibody for 16 min followed by incubation with the Cy5 fluorophore-conjugated tyramide (dilution 1:50) diluted in 1X Plus Amplification Diluent for 8 min. Slides were removed from the instrument and washed twice in EZ Prep buffer . SlowFade Gold Antifade Mountant with 4′,6-diamidino-2-phenylindole (DAPI) was added, and slides were mounted with coverslips.Leica Aperio VERSA-200 digital pathology scanner was used to visualise immunofluorescence staining. Images were acquired at × 20 magnification using the Andor iXon 888 camera  using the Sequenom MassARRAY® system (iPLEX GOLD) as reported previously . Single eviously , 16.In the ICON7 trial, bevacizumab maintenance therapy showed an PFS advantage of hazard ratio (HR) 0.81 compared to placebo . A groupVEGF-A and VEGFR-2. The analysis started from investigating the associations between immunofluorescence variables and treatment outcomes (data types 1 and 2), followed by identifying SNPs that were associated with selected immunofluorescence biomarkers in matched patients (data types 2 and 3) and finally exploring the association between the identified SNPs and treatment outcomes (data types 1 and 3).Variables from three types of data were analysed in this study: (1) clinical data, (2) immunofluorescence biomarker data including VEGFR-2 and c-MET expression and (3) genotyping biomarker data for SNPs in The relationship between variables in clinical, immunofluorescence and genotyping data were assessed using one-way ANOVA for continuous variables or chi-squared tests for categorical variables.2 or dichotomisation by median. Assumption of proportionality was verified based on Schoenfeld residuals [P-values ≤ 0.05 in the univariable analysis were selected for subsequent multivariable proportional hazard regression analysis. A backward stepwise method was applied to identify the optimum subset of variables that associated with PFS or OS. Interactions between prognostic biomarkers of interest and treatment arms were included to seek predictive biomarkers that predicted benefit from bevacizumab. To address potential confounding factors, clinical variables that are significantly associated with immunofluorescence biomarkers are included in multivariable models regardless of their association with patient survival. Their interaction with immunofluorescence biomarkers were also interrogated.The pre-treatment prognostic and predictive significance of each variable were assessed by including the biomarker as a sole covariate (univariable) in a proportional hazards model for PFS or OS. Here, prognostic significance refers to whether there is a significant association between a biomarker and survival independent of treatment arms, while predictive significance refers to if the association between a biomarker and survival are significantly different depending on treatment arms. Variables were included in continuous form where possible and were subject to transformation, such as logesiduals . Martingesiduals . CandidaVEGF-A and VEGFR-2 were introduced to explore potential biological mechanisms underpinning the immunofluorescence data. The SNPs were filtered by their association with immunofluorescence biomarkers and those that strongly associated were investigated for their prognostic and predictive significance with respect to PFS/OS using the proportional hazard model described above. Analyses were carried out in accordance with the REMARK guidelines [Genotyping data from idelines  and wereidelines .P = 0.07) (Table P = 0.005), number of vessels (P = 0.004), median vessel size (P = 0.006) and VEGFR-2 expression (P = 0.003); consistent with the concept that angiogenesis is associated with tumour growth and metastasis  and VEGFR-2 expression (P = 0.027) inversely associated with PFS regardless of treatment  in patients treated with bevacizumab  and amount of residual disease  were significant prognostic factors for PFS  (Table LOW (≤ median) and c-MET/VEGFR-2HIGH (> median) groups, data showed that patients with c-MET/VEGFR-2HIGH tumours treated with bevacizumab had significantly reduced OS compared to c-MET/VEGFR-2LOW tumours , VEGFR-2 rs1870377  and VEGFR-2 rs2305945    are independent predictive factors for bevacizumab-associated outcomes, supporting the hypothesis that there are a group of patients whose outcome is adversely affected by treating with bevacizumab. Furthermore, the VEGFR-2 rs2305945 G/G variant is associated with increasing c-MET/VEGFR-2 co-localisation  and VEGFR-2 rs2305945 G/G variant, predicted a worse outcome following bevacizumab treatment. These two multivariable analyses show that c-MET/VEGFR-2 co-localisation and the VEGFR-2 rs2305945 G/G variant are independent predictive factors for bevacizumab-associated outcomes; supporting the hypothesis that there are a group of patients whose outcome is adversely affected through treatment with bevacizumab.In our initial studies of biomarkers that predict benefit from bevacizumab in ovarian cancer, we identified a group of patients who appeared to be disadvantaged by bevacizumab , 9. The The immunofluorescence image analysis reported here provides the first clinical data from a prospective clinical trial supporting c-MET/VEGFR-2 heterocomplex formation as a putative resistance mechanism against VEGF inhibition . The intThe HGF/c-MET axis can be inhibited through small molecule tyrosine-kinase inhibitors or monoclonal antibodies directed against either c-MET or HGF. Two oral small-molecule multi-kinase inhibitors with activity against c-MET: cabozantinib  and crizVEGFR-2 rs2305945 G/G variant was found to be significantly associated with c-MET/VEGFR-2 co-localisation and while the co-localisation predicted worse outcome from bevacizumab in OS, the SNP predicted worse outcome from bevacizumab in PFS. Worse outcomes from bevacizumab, though not significant, were observed in patients whose tumours manifested both c-MET/VEGFR-2 co-localisation and VEGFR-2 rs2305945 G/G variant. However, it should be noted that this analysis was carried out in a small cohort of bevacizumab-treated patients with both immunofluorescence and genotyping data available and evaluation of the impact of the two factors on survival is confounded by the potential that the SNP could influence c-MET/VEGFR-2 heterocomplex formation.We were interested in VEGF pathway-related SNPs that pertained to the c-MET/VEGFR-2 heterocomplex. The VEGFR-2 rs2305945 and c-MET/VEGFR-2 expression, the question is whether there is any evidence for a biological role of this SNP in the c-MET/VEGFR-2 heterocomplex? Although this SNP is located within a non-coding region of VEGFR-2, there are data suggesting it is of clinical interest. Indeed, previous data has reported that rs2305945 is associated with differential response to VEGF inhibitors in age-related macular degeneration and also protective against ovarian hyperstimulation syndrome [Accepting that there is an association between syndrome , 30. TheThe main strength of the clinical data reported in this study is that it was prospectively collected, although it represents only a proportion of the patients recruited to ICON7. In addition, genotyping biomarker assessment was performed using an established methodology , 16. As The main limitation of our study is the sample size, with 11.6% (178/1528) and 29.4% (449/1528) of women from ICON7 donating tumour tissue and/or blood, respectively. It is notable however, that donation of research tumour tissue and/or blood samples was optional, and not mandated within the trial protocol. Therefore, the sample size reflects the proportion of women willing to donate translational research samples. Moreover, the number required to detect differences in c-MET/VEGFR-2 co-localisation, according to the statistical power consideration, was achieved in the study. Another limitation of this biomarker study is the absence of an independent validation cohort and this could be assessed in an appropriately powered prospective study.VEGFR-2 rs2305945 G/G variant, which may be biologically related, was associated with worse survival outcomes. In patients who did not receive bevacizumab, high c-MET/VEGFR-2 co-localisation showed no association with outcome.In conclusion, in bevacizumab-treated patients diagnosed with EOC, high c-MET/VEGFR-2 co-localisation on tumour tissue and the Additional file 1: Figure S1- Examples of tissue microarray immunofluorescence staining for VEGFR-2 and c-MET. Figure S2- Progression-free survival for VEGF-A rs3025033 and VEGFR-2 rs1870377 SNPs in the control (chemotherapy) and experimental (chemotherapy plus bevacizumab) group. Figure S3- Summary of findings for c-MET/VEGFR-2 co-localisation and SNP VEGFR-2 rs2305945.Additional file 2: Table S1- Characteristics of immunofluorescence biomarkers and their association with demographic data. Table S2- Prognostic and predictive biomarkers assessed as significant in the univariable analysis. Table S3- List of the 35 SNPs in VEGF-A and VEGFR-2 tested and their association with c-MET/VEGFR-2 co-localisation. Table S4- Frequency of three key SNPs in VEGF-related genes. Table S5- Relationship between c-MET/VEGFR-2 co-localisation and VEGFR-2 rs2305945 SNP.


The phenomenon of antibiotic resistance is a global problem that affects the use of antibiotics by humans and animal husbandry. One of the primary reasons for the growing phenomenon of antibiotic resistance is the over-prescription of antibiotics by doctors in human medicine and the overuse of antibiotics in industrial animal farming. Adequate education of veterinary medical students on the use of antibiotics in animal husbandry may reduce antibiotic resistance. For this reason, a survey was conducted among students at four primary research and didactic centers teaching veterinary medicine in Poland. The survey aimed to find out the knowledge and attitude of students towards the use of antibiotics and antibiotic resistance. The survey was conducted in May/June 2021. Four hundred and sixty-seven students participated in the study. The study positively verified that antibiotics and antibiotic resistance knowledge increase with successive years of veterinary studies/education. For most students (82.2%), antibiotic resistance is a significant problem, but only 58.7% believe it is global, and one in three respondents heard about the One Health approach. Since their discovery, antibiotics have been broadly used to treat infections in humans and veterinary medicine. Moreover, they have been used to treat animal infections and, as growth promoters, to enhance production performance in the agriculture sector . HoweverOne of the critical actions required to combat resistance is to increase knowledge regarding the causes and consequences of the overuse and misuse of antibiotics, increasing awareness of antibiotic resistance . Veterinn = 358, 76.7%), which corresponds to the gender-demographic distribution of veterinary students in Poland. The study group was homogeneous in terms of ethnicity and diverse in terms of provenance. Most respondents came from urban areas , and one in three respondents came from rural areas . The selected characteristics of the study group are shown in A total of 467 veterinary medicine students from four academic centers participated in the study. Student participation by the academic year was roughly equivalent, except for 6th year, when the number of full-time classes is minimal, and students are mainly involved in clinical rotations. Most of the respondents were female  had taken antibiotics in the past year, and 25.3% (n = 118) had taken antibiotics 1–2 years ago. The vast majority of students  used an antibiotic prescribed by a physician or dentist, 4% received an antibiotic from a family member/friend or used leftovers from previous treatment, 1% used an antibiotic prescribed by a veterinarian, and 1% purchased an over-the-counter antibiotic from a pharmacy. Most respondents used the prescribed antibiotic as recommended by their physician   .n = 332, 71.1%) rated their knowledge of antibiotics positively/adequately, while 28.9% (n = 135) as poor  than students in years IV–VI .Most survey participants  indicated that they learned about the growing problem of antibiotic resistance during their studies. In this group of students, 73.9% (n = 309) rated their knowledge rather positively/as adequate and 26.1% (n = 109) rather inadequate/negatively.The vast majority of respondents  indicated that participation in classes (veterinary college classes) influenced/motivated/inspired them to learn more about antibiotic use in humans  than in years IV–VI  (p < 0.001).Seven out of ten students  indicated that (veterinary college) participation in classes influenced them to learn about animal antibiotic use  stated that the knowledge imparted/acquired at the university did not influence their knowledge of the use of antibiotics in animals. This was more common among students in years I–III  than IV–VI  (p < 0.001). Most respondents  indicated that the knowledge gained in college had no effect on negating the therapy ordered by a veterinarian for their own or their friends’ pet’s illness  declared that they had not encountered a situation in which a veterinarian prescribed an antibiotic for personal use  than students of years I–III  (p < 0.001). Half of the respondents  would self-prescribe an antibiotic for personal use ad usum prioprium (n = 225) of survey participants would not do so. Respondents representing older (IV–VI) years were more likely to declare that they would self-prescribe an antibiotic for personal use  than respondents of younger (I–III) years  (p < 0.001).Most respondents  and are effective against bacteria . They also are aware that “improper use of antibiotics can cause microorganisms to become resistant” . Most students  disagree that “using antibiotics will make people resistant to them”, and 22% of the respondents agreed with this statement. In this group, 57% were students from years I–III and 43% from IV–VI (p = 0.005). More than half of the respondents  expressed that the “use of antibiotics often cause side effects”. At the same time, 45% of students disagreed with this statement. This opinion was expressed slightly more often by students in years I–III  than IV–VI  (p = 0.257). Most students  agreed with the statement that “bacteria pass information about antibiotic resistance to each other”  would like to increase their knowledge regarding antibiotic use in animals. Six in ten respondents  said they would check antibiotic information and recommendations in another source before starting their doctor-ordered treatment. One in three  would start the treatment fully trusting the doctor.Nearly all respondents  would check antibiotic information from another source before starting a treatment ordered for their pet by a veterinarian.Half of the respondents (p < 0.001). At the same time, 45% of respondents would start the treatment fully trusting the doctor. This opinion was expressed by more students in years I–III  than students IV–VI  (p < 0.001).Among those who gave the above response, 50% represented years I–III and 50% years IV–VI , from a veterinarian , on the Internet , and in hard copy literature .Students declared that they would seek information about the use of an antibiotic when treating their pet or the pet of someone close to them: in the drug leaflet  believe that the issue of antibiotic resistance is a significant problem. At the same time, 17% of the students think it will only become a problem in the future. Most students perceive the problem of antibiotic resistance at a global level , one in nine at an EU level (11%), and one in eight at a national level (12%). One in eight respondents (12%) answered “don’t know/difficult to say”.Most students  had heard of the One Health approach. On average, one in seven students had heard of the National Antibiotic Program  and European Antibiotic Awareness Day .One in three respondents  and the overuse of antibiotics by physicians  have the most significant impact on the growing phenomenon of antibiotic resistance. In contrast, the use of antibiotics without a prescription (self-medication) has the most negligible impact  as well as the overuse of antibiotics by dentists   .n = 354, 75.8%) believe there are current recommendations for using antibiotics in specific clinical situations for animal species in veterinary medicine. At the same time, one-fifth  do not know these recommendations. Of this group, 77% were students in years I–III and 23% in years IV–VI (p < 0.001).Most students  are aware of the increasing antibiotic resistance. They are familiar with the general mechanisms of antibiotic action and their spectrum of activity. It is evidenced by the fact that 97% of respondents negated the effectiveness of antibiotics against viruses and 85% of responses agreed with the statement that bacteria can pass information about antibiotic resistance among themselves. Polish veterinary students see as the main reason for the rise in antibiotic resistance the low awareness of the dangers of increasing antibiotic resistance due to their overuse in both human and veterinary medicine. Interestingly, all year groups believe that the overuse of antibiotics by physicians is more influential for the rise in antibiotic resistance than overuse in veterinary medicine. According to the students, limited access to microbiological diagnostics and low levels of hygiene in animal husbandry is also crucial in this respect. Data from scientific literature show that the unprecedented increase in antimicrobial-resistant organisms is linked to the massive use of antimicrobial agents for infection treatment and prevention ,26,27. TPatient attitudes also contribute to inappropriate and excessive antibiotic use. More than half (60.4%) of the students in our study had taken an antibiotic in the past 24 months, and more than one-third had taken antibiotics in the past year. This result is higher than the answers given by Polish respondents participating in the Eurobarometer 2018 survey, where 24% had taken antibiotics in the last year . On the ad usum proprium.According to the veterinary students surveyed, most of the antibiotics (93.1% cases) were prescribed by a physician or dentist. However, it should be noted that the remaining respondents declared that they used the antibiotic leftover from the previous therapy, donated by a family member or friend, or purchased at a pharmacy without a prescription. Given the importance of antimicrobial resistance worldwide, irrational use of antibiotics and the prevalence of antibiotic self-medication continue to be significant issues affecting the inappropriate and overuse of this group of drugs. In a 2016 survey of medical, pharmacy, veterinary, dental, and nursing students from 25 UK universities, more than a third (86/242) had taken antibiotics in the past year, of which 3.5% had received antibiotics from friends or family . As indiIn addition to the use of self-medication, our study indicates that veterinary medical students show an increased willingness to question prescribed therapy by physicians and treatments recommended by veterinarians. Perhaps this is linked to increasing awareness of existing recommendations for antibiotic use in specific clinical situations in animals. On the other hand, it may also be a symptom of lack of trust in colleagues and lack of humility .The transmission of antimicrobial-resistant bacteria from animals to humans through the food of animal origin is well documented . The firIt is additionally worth noting that one in five respondents (20.8%) disagree with the statement that the overuse of antibiotics by physicians causes the phenomenon of antibiotic resistance. Additionally, two-thirds (66.8%) do not perceive a threat for this issue in the context of possible antibiotic overuse by dentists. Meanwhile, general practitioners and dentists are responsible for nearly 80% of all antibiotic prescriptions written ,47. TherStudents agree that the public is not adequately informed about veterinary aspects of public health provision. Similarly, most students rate the public’s knowledge about antibiotics as very low. It is also puzzling that respondents who were aware of and declared knowledge about the One Health program, the National Antibiotic Program, or European Antibiotic Awareness Day were in the vast minority. In the era of ever-increasing antibiotic resistance of microorganisms, the above facts should persuade relevant institutions (including universities) to pay particular attention to promoting and broadening this knowledge to raise the awareness of the public, including future veterinarians. Promoting One Health attitudes among future veterinarians is especially important due to the emergence of new zoonotic diseases. For this reason, veterinary degree programs should be reformulated under this concept .Given that 99% of respondents expressed a desire to further increase their knowledge of antibiotics, it would be appropriate to revise the scope of curriculum and perhaps expand on topics related to antibiotics and antibiotic resistance. Although evaluating the curriculum was beyond the aim of this study, paying more attention during teaching to issues related to the prudent use of antimicrobials will undoubtedly lead to greater awareness of this topic in future veterinarians. These observations coincide with a recent study that was a joint initiative of the ESCMID Study Group on Veterinary Microbiology (ESGVM) and ESGAP to identify needs and gaps in the antimicrobial stewardship education of European veterinary students . This stTo fully appreciate the value of the conducted research, some limitations are also worth noting. First, it turns out that—as declared by the respondents to the question about the reasons for choosing the field of study—many people study veterinary medicine by coincidence or because they found it an exciting profession. For this reason, their knowledge of antibiotic use in veterinary medicine, especially in the first years of studies, is more imagined than real. It is especially true when they do not have an animal of their own treated with antibiotics by a veterinarian or their parents do not run a farm-based on animal husbandry. Second, although the students declared a high level of knowledge about antibiotics, compared to the average level of knowledge of the whole society on this topic, their knowledge about antibiotic resistance is much lower than declared. Therefore, it should be assumed that the answers to the knowledge questions do not always correspond to the actual knowledge acquired during the studies. Third, the study showed that the higher the year of veterinary medicine study, the higher the knowledge of antibiotic use and antibiotic resistance. Therefore, it would be expected that students in their final sixth year of study would have the most knowledge. Unfortunately, due to the special nature of this year and die to the epidemiological situation caused by COVID-19, it was difficult to reach an adequate number of students from this year. Sixth year veterinary students should be considered underrepresented in this study.The survey was conducted between May and June 2021. Students from four faculties of academic centers in Poland that run the field of veterinary medicine were invited to participate in the study. These were: Faculty of Veterinary Medicine of the University of Life Sciences in Lublin, Faculty of Veterinary Medicine of the Warsaw University of Life Sciences, Faculty of Veterinary Medicine of the University of Life Sciences in Wrocław, Faculty of Veterinary Medicine of the University of Warmia and Mazury in Olsztyn. The key to selecting universities for the study was that they are located in geographically different parts of Poland and are situated in more and less urbanized regions. They are also faculties of veterinary medicine, which occupy the first four places in the ranking of faculties of veterinary medicine in Poland.n = 5200), the maximum error was 3%, for a confidence level of 95% and a fraction size of 0.5.The number of students majoring in veterinary medicine in Poland is approximately 5200. From the selected four centers, the number of students who could potentially participate in the study was 3800. Four hundred and sixty-seven students participated in the study. The study sample was representative of veterinary medicine students in Poland. Considering the size of this sample and the number of veterinary medicine students in Poland (The questionnaire used in this study is a modified version of a questionnaire created by the authors of a survey of attitudes and knowledge about antibiotics among human medical students . The original questionnaire was expanded to include questions about antibiotic therapy and replacement therapy in veterinary medicine and animal husbandry. Changes to the questionnaire were based on the latest knowledge in antibiotic resistance, veterinary medicine, and sociology available to the study’s authors. The questionnaire consists of 4 sections: Demographics, General knowledge, Awareness of functioning programs promoting antibiotic awareness, Knowledge of resistance transmission, and alternative treatments.The survey questionnaire consisted of 41 questions, and the questionnaire took an average of 30 min to complete. The questionnaire was distributed using a link to the Google Forms application. Four coordinators handled the distribution of the questionnaire at each of the selected universities. The questionnaire was distributed online due to epidemiological restrictions introduced by the Ministry of Health and—resulting from this—the implementation of classes at universities in remote form.A pilot study preceded the actual survey to verify and evaluate the prepared tool. Nineteen students participated in the pilot study. Pilot participants made some minor comments, which were considered in the final version of the questionnaire.p-level of <0.05 was considered statistically significant.Cross-tabulations and chi-squared tests evaluated selected factors in antibiotic use and antibiotic-resistance incidence versus student knowledge. All statistical analyses were performed in IBM SPSS Statistics 27.0.1.0. For all analyses, a Consent to conduct the survey among students of Faculty of Veterinary Medicine at the University of Warmia and Mazury in Olsztyn, Faculty of Veterinary Medicine at the Warsaw University of Life Sciences, Faculty of Veterinary Medicine at the University of Life Sciences in Lublin, and Faculty of Veterinary Medicine at the Wroclaw University of Environmental and Life Sciences were also expressed by Deans of the Faculties mentioned above. Study participants were informed that the study was anonymous and confidential, and no personal information, including computer IP, was collected. Results were collected and analyzed collectively to prevent any possibility of identifying the study participant.Most of the surveyed veterinary students pointed out that antibiotic resistance is a serious problem. At the same time, a large group still does not think it is a global problem. The students stated that the phenomenon of antibiotic resistance is influenced by overuse and abuse of antibiotics both in veterinary medicine and medicine and animal production, as well as the low awareness of the phenomenon not only by general public but also by professionals’ low hygiene of breeding and animal production contribute to the dissemination antibiotic resistance.The study suggests that it is necessary to increase the level of antibiotic knowledge of veterinary students especially related to their practical use in their future work as veterinarians, and to pay more attention to universal education on the phenomenon of antibiotic resistance.


The paper reports experimental research regarding the mechanical characteristics of concrete reinforced with natural cellulosic fibers like jute, sisal, sugarcane, and coconut. Each type of natural fiber, with an average of 30 mm length, was mixed with a concrete matrix in varying proportions of 0.5% to 3% mass. The tensile and compressive strength of the developed concrete samples with cellulosic fiber reinforcement gradually increased with the increasing proportion of natural cellulosic fibers up to 2%. A further increase in fiber loading fraction results in deterioration of the mechanical properties. By using jute and sisal fiber reinforcement, about 11.6% to 20.2% improvement in tensile and compressive strength, respectively, was observed compared to plain concrete, just by adding 2% of fibers in the concrete mix. Bending strength increased for the natural fiber-based concrete with up to 1.5% fiber loading. However, a decrease in bending strength was observed beyond 1.5% loading due to cracks at fiber−concrete interface. The impact performance showed gradual improvement with natural fiber loading of up to 2%. The water absorption capacity of natural cellulosic fiber reinforced concrete decreased substantially; however, it increased with the loading percent of fibers. The natural fiber reinforced concrete can be commercially used for interior or exterior pavements and flooring slabs as a sustainable construction material for the future. The construction industry around the world consumes huge volumes of non-renewable materials. This action not only causes wastage of minerals in millions of tons, but also the emission of carbon dioxide, which pollutes the environment ,2. In thPortland cement concrete is brittle in nature and exhibits a relatively lower tensile strength, limited ductile properties, and limited resistance to cracking. Micro cracks exist inside the structure of concrete and result in a poor tensile strength because of crack propagation with time, and lead to brittle fractures. In plain Portland cement concrete and other similar brittle materials, the shrinkage during drying also causes micro cracks. When load is applied on these materials, the micro cracks propagate, and the size of cracks gradually increases causing an inelastic deformation in the concrete material. Therefore, the addition of small size natural fibers in concrete, which are uniformly distributed and randomly oriented, can reduce the drying shrinkage by arresting the propagation of micro cracks and at the same time increasing the strength. This addition of fibers in concrete is known as fiber reinforcement of concrete. The addition of steel as a reinforcement material in concrete reduces the formation of micro cracks while improving the mechanical performance. However, with the passage of time, steel gets rusted due to various oxidative reactions. On the other hand, the reinforcement of renewable natural fibers in concrete is an environment friendly approach and incurs lower production costs ,11,12. SSeveral researchers reported findings on the reinforcement of jute fibers in concrete in order to increase the compressive, bending, and impact strengths ,21,22. TThe fracture energy of natural fiber reinforced concrete using elephant grass, hemp, and wheat straw has been reported . ConcretThe current research is focused on an experimental investigation of the mechanical characteristics in natural origin sustainable cellulosic fiber-reinforced concrete. Jute, sugarcane, sisal, and coconut fibers with average length of 30mm were mixed with concrete matrix in varying percentages (0.5–3%) of cement mass. The results were also compared with the control samples (without fiber reinforcement) and the improvement in mechanical properties by adding natural fibers was quantified. Statistical analysis was carried out using design of experiment (DoE) and analysis of variance (ANOVA) methods in order to quantify the significance and the contribution of experimental parameters on the mechanical and water absorption properties in concrete samples reinforced with natural cellulosic fibers.The constituents of natural cellulosic fiber-reinforced concrete investigated in this work are ordinary Portland cement (OPC), gravels/aggregates, fine sand, and selected natural fibers. Different varieties of natural cellulosic fibers were used for the preparation of the concrete samples. Jute fiber was selected from the category of bast fibers. Among the leaf fibers, sisal was selected. From the category of fruit fiber, coconut/coir fibers, and from cane fiber category, sugarcane bagasse, were chosen. Bagasse is a waste product of the sugar cane industry. All these fibers show a high strength/weight ratio as well as a high aspect ratio. Coconut/coir and jute fibers were obtained from Pakistan, sisal fiber was purchased from China, and sugarcane bagasse fibers were manually extracted from sugarcane as reported in the literature ,45,46,47Apart from sugarcane, all other fibers were procured in finished form. Sugarcane bagasse was obtained from the agricultural waste by a manual scutching process. After the juice was squeezed/extracted from the plant, the fibrous stem was disposed as waste. These stems were collected, thoroughly washed, and then dried. The fibers were individualized by a scutching/beating operation. All the fibers were cut into 30 ± 2 mm length. The jute, sisal, and coconut/coir fibers were procured from the market. However, the properties were evaluated in the laboratory. Some basic properties were taken from the literature . All of The chemical ingredients of ordinary Portland cement (OPC), as obtained from the supplier, are given in The detailed characteristics of the natural fibers utilized are presented in In order to prepare the concrete samples with cellulosic fiber reinforcement, a 1:2:4 volume ratio of cement, sand, and gravel was maintained. The water/cement proportion of 0.55 by mass was kept for all samples . The natMicroscopic analysis was done for the fibers using scanning electron microscopy  and for the fracture surface of concrete samples after mechanical testing using light microscopy. The samples were prepared with a sputter named Quorum Q150R ES , using gold-plating in an argon gas atmosphere. The thickness of the gold plating was 2 nm, and a current of 20 mA was used. A magnification of 10,000× was used for SEM and 100× was used for analyzing the fracture surface of the samples .In order to check the mechanical performance and durability of the natural cellulosic fiber reinforced concrete samples as compared to plain concrete, the splitting tensile strength, bending strength, compressive strength, impact test, and water absorption tests were conducted. The mechanical test principles are shown in tS = splitting tensile strength, P = pressure for cracking, D = diameter of specimen, and L = length of specimen.The splitting tensile testing of concrete samples with a cylindrical shape (diameter = 7.4 cm and length = 13 cm) was determined by Digital-Display Hydraulic Universal Testing Machine  with testing standard ASTM C496-96 . The loaP represents load, L represents gauge length, b represents width, and h represents thickness. Ten measurements were carried out and the average was reported.To measure the bending strength of the samples, rectangular concrete blocks (13 cm × 2.56 cm × 2.56 cm) were made as per the ASTM standard. The Hydraulic Universal Testing Machine (Model: Beijing Sinofound WES-100) was used to measure the value of the bending strength. The test standard ASTM C78/C78M-21 was used [The compressive testing of natural fiber reinforced samples and plain concrete samples of cubic size (5.2 cm × 5.2 cm × 5.2 cm) were determined by a Digital-Display Hydraulic Universal Testing Machine (Model: Beijing Sinofound WES-100) with testing standard ASTM C109/C109M-07 . The loaM = mass of impactor, g = acceleration due to gravity, and h = drop height of the impactor.The impact strength was measured using rectangular blocks (size 10.2 cm × 13.4 cm × 2.56 cm). The drop weight impact tester  was used to measure the energy absorbed by the samples according to the ASTM C1747_C1747M-13 standard . A maximTen measurements were conducted for each type of mechanical property and the mean was reported with coefficient of variation (CV% < 5%). All results were considered for calculation of the mean. In case some results were out of scale (CV > 5%), the measurements were repeated.cK = effective mechanical property of the fiber reinforced concrete; fK and mK are the corresponding fiber and concrete mechanical properties, respectively; fV = the fiber volume fraction; and ζ = geometrical parameter, which represents the loading conditions .For theoretical estimation of mechanical properties of the fiber-reinforced concrete, the corresponding mechanical properties of the fibers and pure concrete were evaluated experimentally. The mechanical properties of the cellulosic fiber reinforced concrete were estimated using Halpin–Tsai model. This model is commonly used for prediction of the effective mechanical properties of fiber-reinforced concrete (composite) with well-defined fiber alignment ,34,35. TIn order to measure the water absorption capacity (%) of fiber reinforced concrete samples comparative to plain concrete samples, blocks of cubic size 5.2 cm × 5.2 cm × 5.2 cm were prepared. The water absorption (%) was checked on Specific Gravity apparatus  with electronic balance using the ASTM C127-04 testing standard . A mean For statistical analysis, full factorial design of experiment (DoE) was used . Table 3Analysis of variance was used to check the significance of the experimental parameters affecting the mechanical and durability functions of the concrete samples at the 95% confidence interval. Minitab 17 software was used for this purpose.Cross-sectional images of the fiber samples were taken using scanning electron microscopy (SEM), as shown in It can be observed that the four types of fibers used in this study contained a large amount of air due to the pores in their microstructures. As compared to jute and sisal, the coir and bagasse fibers showed a higher porosity. They had a higher diameter and thus a more open structure.For all the fiber types  of reinforced concrete samples, the compressive strength gradually increased with the increase in percentage of natural fibers in concrete up to 2% fiber loading. Beyond this limit, the compressive strength further decreased. In the case of 0.5% jute and sisal fiber reinforcement, an increase of 11.6% to 20.2% in compressive strength was observed compared to plain concrete. Furthermore, 0.5% coconut fiber reinforcement in concrete increased the compressive strength by about 9%. Increasing the fiber loading up to a maximum of 2% resulted in an increase of the compressive strength in natural fiber reinforced concrete samples. Such observations are based on the rule of mixture and have been reported by several other researchers ,8,9. A fThe differences in behavior of concretes with different types of cellulosic fibers follow similar trend as the respective fiber mechanical properties. As the jute and sisal fibers have inherently superior mechanical properties compared to coconut and sugarcane, the same effect is reflected in the concrete samples reinforced by the respective fibers. This trend is consistent for all the different fiber loadings up to 2%. As per Halpin−Tsai model the mechanical performance depends on the fiber and matrix (concrete) mechanical properties and fiber volume fraction. In case of higher fiber loadings, the decreasing trend may be attributed to irregularities in fiber orientation and the presence of voids due to a higher fiber percentage.For all the natural fiber-reinforced concrete samples, the tensile strength gradually increased compared to the control sample, with an increasing fiber loading percent up to 2%. The increase in tensile strength by varying quantity of natural fibers for jute, sisal, sugarcane, and coconut fiber reinforced concrete samples is 60.4% to 137.7%, 51% to 103.8%, 3.8% to 34%, and 34% to 73.6%, respectively. The tensile strength of fiber-reinforced concrete depends on the tensile strength of the reinforcing fibers. The tensile strength and tenacity of the fibers is in the order jute > sisal > coconut > sugarcane. A similar trend in the concrete samples reinforced by such fibers is observed. The observations are confirmed by theoretical calculation of the tensile properties based on the Halpin−Tsai model, as given in The microscopic images shown in However, it was observed that the tensile strength further decreased as the fiber loading increased to 2.5% and 3%. These findings were along the same line as the compression properties. It might therefore be concluded that a fiber loading higher than 2% results in a decrease in strength of natural fiber-reinforced concrete. This is again attributed to irregularities in fiber distribution and resulted in voids in the concrete.The results in Bending strength increased with increasing the loading percent of fibers up to 1.5%. Increasing the fiber loading beyond 1.5% in concrete caused a visible decrease in the bending strength. Concrete samples reinforced with jute and sisal fibers exhibited a superior bending strength as compared to the coconut and sugarcane fiber reinforced samples. The bending properties of fiber-reinforced concrete also depended on the tensile properties of the fibers. Thus, an increase in bending strength was clearly based on the fiber tensile properties. Up to 1.5% fiber loading, the Halpin−Tsai equations predicted the bending performance. The results are given in These observations support several previous researchers ,7,8,9. TFor all the natural fiber  reinforced concrete samples, the capacity of water absorption increased with a higher fiber loading percentage. The overall water absorption capacity of the natural cellulosic fiber-reinforced concrete varied in the range of 4.25% to 9.25% by changing the fiber loading percentage from 0.5% to 3%. As observed from the fiber−concrete interface images in The analysis of variance was used to find the significance of the natural fiber type and loading percent on the mechanical and durability/water absorption performance of concrete. The ANOVA results show that experimental factors like type of natural fiber reinforcement and the loading of fiber have a significant influence on several aspects of the mechanical performance of concrete, e.g., compression, tensile, bending, and impact strength. Furthermore, the type and amount of fiber loading has a significant influence on the water absorption capacity.The mechanical performance of natural cellulosic fiber-reinforced concrete was observed to improve up to a certain limit for fiber loading. With a further increase in the loading percent of natural fibers, there is decrease in tensile, bending, compressive, and impact performance. Such behavior at a fiber loading higher than 2% is attributed to cracks and voids due to irregular fiber orientation, and thus the initiation of the mechanical failure in concrete.The results reveal that the compressive strength of natural fiber-reinforced concrete increases with fiber loading up to 2%. For jute and sisal fiber reinforcement, about a20.2% and 11.9% improvement in compressive strength, respectively, was observed compared to the plain concrete.The tensile strength of natural fiber-based concrete gradually increases with the increase in percentage of natural fibers in concrete. The increase in tensile strength for jute-, sisal-, coconut-, and sugarcane fiber-based samples is up to 137.7%, 103.8%, 73.6%, and 34%, respectively by varying percentages of fibers up to 2%.While the bending strength of the natural fiber reinforced concrete samples increased by increasing the fiber loading until 1.5%, there was a decrease beyond 1.5%. At 1.5%, the bending strength was observed to be at a maximum for the jute fiber reinforced concrete sample (0.369 MPa) followed by sisal-based concrete (0.291 MPa), coconut (0.254 MPa), and sugarcane fiber reinforced concrete (0.246 MPa).The energy absorbed by the fiber reinforced concrete increased with the increase in percentage of natural fibers up to 2%, and hence the impact strength increased. The maximum energy (J) absorbed was observed for jute fiber-based concrete, which was 1.87 J followed by sisal, coconut, and sugarcane-based samples, which absorbed energy of 1.84 J, 1.44 J, and 1.31 J respectively.In the natural fiber reinforced concrete, the water absorption capacity gradually increases with the increase in percentage of fibers. The inter fiber and interfacial porosity of coconut- and sugarcane fiber-based concrete enables a higher water absorption compared to jute and sisal fiber-based concrete.The natural cellulosic fiber-reinforced concrete offers numerous scopes for the replacement of pure concrete in slabs and pillars. Thus, a sustainable building material with an enhanced mechanical and durability performance can be commercially produced. Furthermore, the material can be made more economical by using agricultural and industrial waste fibers.


The use of antipsychotic medications is associated with side effects, but the occurrence of severe tachycardia (heart rate ≥ 130 per minute) is not well described. The aim of this study was to determine the frequency and strength of the association between antipsychotic use and severe tachycardia in an inpatient population of patients with mental illness, while considering factors which may contribute to tachycardia. We retrospectively analyzed data from 636 Medical Emergency Team (MET) calls occurring in 449 psychiatry inpatients in three metropolitan hospitals co-located with acute medical services, and used mixed-effects logistic regression to model the association between severe tachycardia and antipsychotic use. The median age of patients was 42 years and 39% had a diagnosis of schizophrenia or psychotic disorder. Among patients who experienced MET calls, the use of second-generation  antipsychotics was commonly encountered (70%), but the use of first-generation  antipsychotics was less prevalent (10%). Severe tachycardia was noted in 22% of all MET calls, and sinus tachycardia was the commonest cardiac rhythm. After adjusting for age, anticholinergic medication use, temperature >38 °C and hypoglycemia, and excluding patients with infection and venous thromboembolism, the odds ratio for severe tachycardia with antipsychotic medication use was 4.09 (95% CI: 1.64 to 10.2). In patients with schizophrenia and other psychotic disorders, antipsychotic medications relieve hallucinations and delusions, improve thought disorder, behavior and quality of life, and ultimately allow patients to function in society . AntipsyAntipsychotic medications are associated with multiple adverse effects. Among these, several mechanisms may contribute to tachycardia, such as the anticholinergic properties of antipsychotics, postural hypotension due to α1-adrenoreceptor blockade, and indirect effects such as myocarditis and neuroleptic malignant syndrome ,3. Most In Australia, New Zealand, and other countries, a rapid response team such as the hospital Medical Emergency Team (MET) is activated upon recognition of worsening vital signs or clinical concern in a hospitalized patient. The MET call brings critical care expertise to the bedside to evaluate and stabilize deteriorating patients . In psycThe aims of this study were to determine the frequency and strength of the association between antipsychotic medication use and severe tachycardia at MET calls in an inpatient population of patients with mental illness, while considering other factors which may contribute to tachycardia in a hospitalized patient.We conducted a cross-sectional study of all patients who had a MET call during their admission to a Monash Health psychiatric facility from January 2015 to January 2020. The Monash Health hospital network is in the state of Victoria, Australia and provides healthcare services to the south-east region of the city of Melbourne. Within the network, three hospitals  have inpatient psychiatric services that are co-located with acute medical services, which provide 24-h onsite MET availability. The inpatient capacity across the three sites is 188 beds, comprising general adult psychiatry, mother–baby unit, aged psychiatry (≥65 years), and a secured extended care unit (SECU) for patients requiring medium to longer term treatment for unremitting and severe symptoms.We searched our central electronic incident reporting system (RISKMAN) for adult psychiatry inpatients ≥18 years who experienced a MET call during the study period at any of the three sites. We excluded cases with inadequate or missing documentation of the MET call, any duplicated entries and patients receiving day treatment who were incorrectly identified as an inpatient, and visitors to the ward. We also excluded patients returning from a leave of absence within the previous 24 h, as these patients may have MET calls and tachycardia related to illicit drug use.The Monash Health Human Research Ethics Committee approved this study as a quality improvement initiative and waived the need for patient consent (RES-20-0000281Q-63108).For this study, MET calls and MET calls which progress to Code Blue (cardiopulmonary arrest) were considered together. Our hospital guidelines mandate MET activation if any one or more of the following criteria are fulfilled: (1) respiratory distress, (2) concern of the airway, (3) respiratory rate >30/min or <6/min, (4) oxygen saturation <90%, (5) systolic blood pressure <90 mm Hg, (6) heart rate >130/min or <40/min, or (7) a sudden decrease in conscious state. Trigger zones are color coded in the observation charts and electronic record. Discretionary MET calls were also allowed for a broader criterion of clinical concern, even if vital signs have not breached the threshold for mandatory MET activation. Such clinical concerns may include, but not limited to chest pain, poor urine output, hypoglycemia, trauma, and self-harm.The main study outcome was severe tachycardia, as defined by the MET call criterion of a heart rate ≥130 per minute. The main factor of interest was antipsychotic medication use, which was grouped into two broad categories: first-generation or conventional antipsychotics, and second-generation or atypical antipsychotics. A comprehensive review of the drug charts was undertaken to identify all psychotropic medications prescribed and any other medication which may be associated with alterations in heart rate. We grouped the other psychotropic medication into categories of antidepressants, mood-stabilizers, and benzodiazepines. We specifically collected data on the use of anticholinergic agents to manage the extrapyramidal side-effects of antipsychotic medications as these can also contribute to tachycardia.From the medical records, we collected demographic information and determined the primary psychiatric diagnosis related to admission. We identified baseline independent variables which could confound the association between antipsychotic medications and tachycardia. They included age, sex, body mass index (BMI) categories , smoking, alcoholism, illicit drug use, recent electroconvulsive treatment (ECT) and the comorbidities of diabetes, a composite of cardiovascular disease , and a composite of chronic lung disease .From the pathology system, we collected data on the serum potassium and magnesium levels measured during the MET call or within 48 h of the MET call. Biochemistry results beyond 48 h of the MET call were considered unreliable for analysis. The laboratory reference range for normal serum potassium was 3.5 to 5.2 mmol/L, and the reference range for serum magnesium was 0.70 to 1.10 mmol/L.We examined the RISKMAN entry and medical record to determine the trigger for the MET call, the observations and assessment of the patient during the MET call , oxygen saturation and temperature), and reviewed the patient’s electrocardiogram (ECG) to determine the underlying rhythm associated with the tachycardia. Finally, we examined the final diagnosis associated with the MET call for additional confounders of tachycardia.2 analysis or Fisher’s exact test. As more than one MET call per patient was possible, we used mixed-effects logistic regression  to test the association between tachycardia and antipsychotic use, and adjusting for several confounders. For variable selection into the multivariable model, we used the purposeful selection method. All variables with a p < 0.25 from the univariable analysis were entered into the multivariable model, followed by backwards elimination of variables with the least statistical significance. Eliminated variables were checked for confounding by assessing the change in the estimated coefficient for antipsychotic use. A change of >10% was considered evidence of confounding. Variables with a p < 0.05 and confounding variables were retained. Fractional polynomials were used to confirm the linearity of the logit for continuous variables in the model. We checked for collinearity by examining the variance inflation factor, and for statistical interaction between the main effect variables at a 1% level. Akaike and Bayesian information criteria were used to compare different possible models. In the final multivariable model, we examined the calibration plot to assess model fit, and we report the cluster-specific  adjusted odds ratios for antipsychotic medication use. Analysis was performed with STATA v16.1. . A p < 0.05 was considered statistically significant.In the descriptive analysis, we report the mean and standard deviation (SD) for data which were normally distributed. For skewed data, we report the median and interquartile range (IQR). We examined the association between two categorical variables using a χA flow diagram of the selection of eligible patients and the reasons for exclusion is shown in t594 = 1.48, p = 0.14). The mean serum magnesium of patients with severe tachycardia was 0.01 mmol/L lower than those without, which was also not significant .At the time of the MET calls, the prevalence of hypokalemia and hypomagnesemia were 3.9% and 8.8%, respectively . The disPatients with schizophrenia and other psychotic disorders comprised a large proportion of the inpatient population, and consequently, antipsychotic medications, particularly the second-generation antipsychotics, were the most frequent class of psychotropic medication used .The top three triggers for a MET call were a drop in GCS or seizure (39.6%), tachycardia (16.8%) and hypotension (16.7%). The other triggers for a MET call included hypoxia (6.4%), tachypnea (2.0%), bradycardia (1.7%), and the rest were for clinical concern such as chest pain, hypoglycemia, and self-harm. On clinical assessment, 137 of 636 (21.5%) of MET calls were associated with tachycardia and a heart rate of ≥130 per min regardless of the MET call trigger. An ECG was performed during 383 (60.2%) of MET calls. Of the 383 ECGs examined, 190 (49.6%) were completely normal, and a detailed description of the abnormal ECGs is presented in The results of the univariable logistic regression analyses are summarized in In the multivariable model , there wp = 0.20) and only changed the estimated coefficient by 7% if dropped from the model, but the effect of hypoglycemia on the coefficient for antipsychotics remained greater than 10%. In Model 4, benzodiazepine use was dropped, and the Akaike and Bayesian information criteria suggested that this model provided the best fit for our data and is our preferred model for inference. In this model, there was no evidence of statistical interaction or multicollinearity among the included variables. The model testing and goodness-of-fit assessment is presented in In the sensitivity analysis, excluding MET calls associated with patients diagnosed with venous thromboembolism or infection (Model 3), the estimated coefficient for antipsychotics changed by 12%. By excluding these patients with reasons for tachycardia, benzodiazepine use was not statistically significant .In patients with severe tachycardia at MET calls, 68 of 137 (50%) were transferred to an acute medical ward. This was identical to the 248 of 499 (50%) of patients without tachycardia who were transferred to an acute medical ward after a MET call. Hence, tachycardia per se did not appear to be a factor associated with transfer. In patients who were transferred, the length of stay in the acute medical ward was not different in tachycardic  vs. non-tachycardic patients , with a In this study of MET calls in an inpatient psychiatric population, we found a positive association between the use of antipsychotic medications and severe tachycardia (heart rate ≥130 per min). A patient in a psychiatric ward who was treated with any antipsychotic medication increased his or her odds of experiencing severe tachycardia and a MET call by 4.1 times the odds if he or she did not use antipsychotic medications, holding age, temperature >38 °C, anticholinergic medication use, and hypoglycemia constant. The odds of tachycardia were even higher if he or she was treated with the first- generation compared to second-generation antipsychotics, although this difference was small and the clinical relevance was unclear.p = 0.20). We did not have statistical power to confirm this association, and it was an a posteriori consideration. However, a previous population-based study reported that the use of antipsychotics was associated with a 17% increased risk of atrial fibrillation compared to non-use, and patients at highest risk were those with hypertension, diabetes, and ischemic heart disease [Cardiovascular side-effects of antipsychotic medications are well known. Sudden death and ventricular arrythmias associated with prolongation of the QT interval is the most dreaded ,6. HowevThe association between antipsychotics and severe tachycardia in our study raises questions regarding the long-term risk of tachycardia-induced cardiomyopathy (TIC), where prolonged tachycardia induces structural and clinical features of heart failure with reduced ejection fraction. Continuous ambulatory monitoring studies have demonstrated that antipsychotic medication use can be associated with persistent tachycardia . In a poTIC may be a phenomenon related to rate-related ventricular dysfunction, with depletion of energy stores and ischemia, oxidative stress, and neurohormonal activation leading to myocardial fibrosis and cardiac structural changes ,11. CathIn our study, there was a small difference in the odds ratio for severe tachycardia and MET calls between the first- and second-generation antipsychotics. Although we assumed a class effect in our analysis, other studies have suggested that individual antipsychotics vary in their side-effect profile (even within the same class of second-generation antipsychotics) and demonstrate a dose-dependent effect, including their effect on heart rate ,19. OtheHypokalemia is associated with abnormal intracellular calcium and sodium metabolism, which can trigger arrhythmias such as ventricular tachycardia/fibrillation, atrial fibrillation, and atrial flutter ,23. In oprn (as needed) breakthrough or supplemental doses. As a cross-sectional study, we cannot prove that tachycardia was sustained or severe and a longitudinal study would be ideal to address this. There were missing observations in our data for potassium and magnesium levels, which may have biased our analysis. A prospective cohort study of patients initiating antipsychotics after a period of baseline monitoring could avoid issues of missing observations and allow accurate quantification of antipsychotic medication exposure, and thus provide better quality evidence for a causal inference. Finally, as we only studied an inpatient population, the results should not be generalized to patients in the community or ambulatory care.One strength of our study was the inclusion of multiple sites and a range of psychiatric diagnoses, which improves the generalizability of the results. We used a multivariable logistic regression model to account for confounders, and used a mixed effects model to account for the influence of random effects  on the parameter estimates. We also collected data on relevant medications which may protect against severe tachycardia or act synergistically with antipsychotics to worsen tachycardia. The main limitation of our study was the cross-sectional design which limits a direct causal inference. We could not factor in antipsychotic medication dosage, which, although relevant, was difficult retrospectively, given titration of doses at the clinician’s discretion, use of long-acting preparations, and the irregular use of Our study confirms a strong association between antipsychotics and severe tachycardia in psychiatric inpatients. The potential for adverse cardiac outcomes in the medium- to long-term due to severe tachycardia is unknown and needs to be further studied to assist in future risk–benefits discussion.


Introduction: This study aims to examine the changes in trends and patterns of clinical consumption of antibiotics in Shandong, China based on Access, Watch, and Reserve (AWaRe) Classification after 10-years national antibiotic stewardship.Methods: Antibiotic consumption data of all health care institutions for the period of 2012–2019 were obtained from the Drug Centralized Bidding Procurement System of Shandong. Shandong is a province that has the second-largest population in China. Five of the 16 cities in Shandong were high-income areas (HIAs) and the other 11 cities were grouped into upper-middle-income areas (UMIAs). The main outcome measures were the antibiotic consumption rates  and the proportions of different groups of antibiotics.Results: The overall antibiotic consumption rate increased from 12.859–15.802 DID between 2012 and 2014, then continuously decreased to 9.771 DID in 2019. The consumption rate of access, watch, and reserve antibiotics have reduced since 2014 with a compound annual growth rate of −10.1, −9.0, and −8.1%, respectively. During 2012–2019, the access group proportion reduced from 50.0 to 44.9%, while the proportion of the watch group increased from 42 to 45.2%. The antibiotic consumption rate increased from 2012 to 2019 (from 7.38 to 9.12 DID) in the HIAs but sharply decreased in the UMIAs from 2014 to 2019 (from 17.94 to 10.05 DID). The watch antibiotics had the highest proportion of consumption in the HIAs (55.3% in 2019), while the access group had the highest proportion of consumption in the UMIA (49.5% in 2019).Conclusion: The antibiotic stewardship policies launched in the last 10 years have contributed to reducing the clinical antibiotic consumption in Shandong. These policies have different effects on areas with different economic levels. The pattern of antibiotic consumption is still inappropriate in China as the watch group of antibiotics was consumed the most. Since the first antibiotic was discovered over 100 years ago, antibiotics have saved thousands of lives suffered from infectious diseases . HoweverChina has a huge pharmaceutical market. In 2020, the total terminal sales of pharmaceutical products reached 1708 billion RMB in China, with 69.4 and 30.6% sold in health care institutions  and retail private pharmacies, respectively . China iThe current published studies conducted in China often focus on the patterns of clinical use of antibiotics in selected tertiary hospitals with findings that indicate a decline in antibiotic prescribing rates . Few stuth among the 34 provincial administrative districts in China  over the period 2012–2019. Shandong is an eastern province of China traversed by the yellow river, with a population of more than 100 million in 2020. The gross national income (GNI) per capita in China and Shandong Province were $10224 and $10506 in 2019 , respectively. In 2020, the gross sales of pharmaceuticals in Shandong province ranks 6in China . There ain China , five ciThe CBP system is an official online medicine trading platform that was established throughout the country in 2009. Health care institutions in Shandong were required to procure all medicines through the CBP system since the end of 2011. Consumption data of the private pharmacies is not available from this system. It records name of region, names of buyer and manufacturer, procurement date, receiving date, generic name of drug, strength, dosage and package, request quantity and unit price. Data of each record of antibiotic consumption between 2012 and 2019 was exported from this system into excel format, then cleaned and analyzed using Stata 16.0.In China, health services are mainly provided by public health care institutions run by the government. In 2019, the total revenue of private health care institutions accounted for only 13% of all health care institutions . We diviAll the procured antibiotics, including antibacterial for systemic use (J01), antimycotics for systemic use (J02), and intestinal anti-infectives (A07A), were standardized according to the Anatomical Therapeutic Chemical and Defined Daily Dose (ATC/DDD) system recommended by WHO . AntibioThe total antibiotic consumption rate increased by 22.9%, from 12.859 DID in 2012 to 15.802 DID in 2014, then continuously reduced at a CAGR of −9.2% between 2014 and 2019 (9.771 DID in 2019). The consumptions of the access, watch and reserve antibiotics also reached their peaks in 2014 , then all kept decreasing during 2014 and 2019 with a GACR of -10.1%, −9.0% and −8.1%, respectively  . The conThe PHC was the leading antibiotic consumer. In 2012, the PHCs consumed 7.4 times as much volume of antibiotics as hospitals (388.4 million DDDs vs. 52.3 million DDDs). From 2014 to 2019, the PHCs saw a sharp fall, from 461.5 to 232.3 million DDDs, at a CAGR of −12.8%. Alternatively, the volume of antibiotics consumed by hospitals, although slightly declined in 2016, has doubled in 2019 (117.2 million DDDs) compared with that in 2012 (52.3 million DDDs). Health service utilization showed similar trends as antibiotic consumption in both the hospitals and PHCs. Outpatient visits and admissions increased at a GACR of 7.3 and 6.3% in hospitals but decreased with a GACR of 0.58 and 3.15% in the PHCs between 2012 and 2019. The consumption of the other group fluctuated during the study period, and it only accounted for 0.8% of the total on average .In hospitals, access antibiotic consumption accounted for about one-third of the total antibiotic consumption. The proportion of access antibiotic consumption decreased yearly since 2015, while the proportion of watch antibiotic consumption maintained at 50–60%. In 2019, the volume of access antibiotics was only about one-half of the volume of the watch antibiotics in hospitals. In the PHCs, the proportions of the access and watch antibiotic consumptions were about 50 and 40%, respectively. The proportion of access antibiotic consumption has been increasing since 2015. By contrast, the proportion of the watch antibiotics consumed in the PHCs tended to decline between 2015 and 2019 .People living in the UMIAs consumed twice as much antibiotics as people living in the HIAs between 2012 and 2014 . The antibiotic consumption rate in the UMIAs having sharply declined at a CAGR of −10.9% since 2014 (17.94 DID) and reached a rate (10.05 DID) close to that in the HIAs (9.12 DID) in 2019. In the HIAs, the antibiotic consumption rate fluctuated slowly from 9.96 DID in 2014 to 9.12 DID in 2019. In both economic-level areas, the volume of antibiotic consumption showed a decreasing trend in the PHCs, while an increasing trend in hospitals. In the HIAs, the volume of antibiotics consumed by hospitals grew at a faster rate (CAGR: 14.7%) than that in the UMIA (CAGR: 10.6%) during the last 8 years and surpassed the volume of antibiotics consumed by the PHCs in 2019 .In terms of access antibiotic consumption, the proportion maintained at approximately 50% in the UMIAs , while decreasing yearly from 41.9 to 33.3% in the HIAs during the study period. The proportion of watch antibiotic consumption showed a trend of growth between 2012 and 2016  and then declined between 2016 and 2019  in both economic-level groups. With quite a small proportion (<1%) in both groups, the reserve antibiotics started to grow in 2015 and doubled in 2019 compared with 2015 (0.69 vs. 0.33%) in the HIAs .amoxicillin (J01CA04), amoxicillin and beta-lactamase inhibitor (J01CR02), and benzylpenicillin (J01CE01). Amoxicillin was also the most consumed antibiotic among all, the consumption of which accounted for 27.2% of the total volume in 2019. Only amoxicillin and beta-lactamase inhibitor showed an increasing trend, while all the other access antibiotics declined over the past four or 5 years. The most commonly consumed watch antibiotic was levofloxacin (J01MA12), followed by cefuroxime (J01DC02) and roxithromycin (J01FA06). All the watch antibiotics showed a downward trend. In the reserve antibiotic group, fosfomycin (J01XX01), minocycline (J01AA08), and linezolid (J01XX08) were the most commonly consumed. Three of the top five consumed reserve antibiotics, which were minocycline (J01AA08), linezolid (J01XX08), and tigecycline (J01AA12) had growth trends in recent years  . The groAlthough China’s antibiotic stewardship policies was mainly targeted at hospitals, the volume of antibiotic consumption still showed an increasing trend in secondary and tertiary hospitals. On the contrary, the consumption of antibiotics at PHCs in Shandong dramatically declined in the last few years. In addition to the policy effect, this may be because China’s PHCs are shrinking while hospitals are expanding. According to the China Health Statistics Yearbook 2020 , the numOverall, there was no obvious change in the proportions of watch antibiotics. The proportion of watch antibiotics was much higher than that of the access antibiotics in the hospitals. However, this proportion decreased and was much lower than that of access antibiotics in the PHCs. This decrease may more likely be related to the effects of regulation which limited the prescription of antibiotics in watch and reserve groups by junior physicians. Therefore, some patients may visit hospitals instead of PHCs for restricted antibiotics. It should be noticed that the classifications of antibiotics in the ACL of Shandong, as well as the other provinces in China is different from those in the AWaRe Classification. All the top five watch antibiotics are grouped into non-restricted antibiotics in the Shandong ACL (2021 version), which may result in a lower policy impact on the watch group than the access one.Globally, the high-income economies consumed more antibiotics per person than the low-or middle-income economies and consumed much more volume of access antibiotics than the watch antibiotics during 2011 and 2015 . HoweverAlthough the consumption rate of reserve antibiotics also decreased in Shandong, it has the lowest reduction rate among all three categories. Linezolid (J01XX08) and tigecycline (J01AA12), two relatively new antibiotics that are often used to treat severe infections caused by multi-drug resistant bacteria , had incThis study has several strengths. First, our study analyzed antibiotic procured by almost all the health institutions in a large-population province in China. Currently, there is no national data analysis on antibiotics consumed by all health care institutions because the CBP system is established at the provincial level and the recorded data is not shared with the other provinces. Since there were few studies focused on antibiotic consumption over the whole province, this study will add a big piece of the puzzle regarding China’s antibiotic consumption. Second, the study period was during 2012 and 2019 when China began to intensively issue antibiotic stewardship policies. Our findings showed a decreasing trend of antibiotic consumption rate, which may likely reflect the effect of the national policies. These policies could be tailored to other countries or areas with similar circumstances. Third, by analyzing the pattern of antibiotic consumption according to AWaRe Classification by regional economic level and types of health care institutions, our study could explore the priorities for future antibiotic governance.Nevertheless, this study is limited by the observational study design and could not prove the causal relationship between policies and changes in antibiotic consumption. Further, because China has launched a series of policies to improve antibiotic use and to control AMR in the last 10 years, it is likely impossible to identify the effect of a single policy. Another limitation is that our study lacked antibiotic consumption data from private pharmacies. According to a study conducted in private pharmacies of China using a simulated client method, 70% adult URTI visits were dispensed with non-prescription antibiotics in 2017 . HoweverThe antibiotic consumption rate in health care institutions has indicated a downward trend in China’s Shandong Province after nearly a decade of antibiotic stewardship. However, the pattern of antibiotic consumption is still inappropriate in terms of the watch group of antibiotics consumed. In addition, the trends for antibiotic consumption were found to vary across areas with different economic levels. Indicating that further investigation is needed to understand the reasons for this variability in policy effects.


Demineralized dentin matrix (DDM) treated with gamma irradiation (GR) has shown promising results as an allograft without any adverse effects in in vivo and clinical studies. The purpose of this study was to evaluate the effects of 15 and 25 kGy GR on the osteoinductive properties of DDM at extra-skeletal sites. As a control group, non-irradiated DDM powder was implanted into the right subcutaneous tissues of the dorsal thigh muscles of 20 nude mice. DDM powder irradiated with 15 and 25 kGy was implanted into the left side. After two and four weeks, the bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. After confirming osteoblast- and osteoclast-specific activities by alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) staining, a histological analysis was performed to measure the new bone formation and the number of osteoblasts and osteoclast-like cells on the surface of the DDMs. Histomorphometry was used to calculate the new bone formation area on the surface of the DDM particles (DDMs). The BMD in all the groups increased from two and four weeks without statistically significant differences. The osteoblasts were dominantly activated on DDM without GR, and DDM treated with 25 kGy compared to DDM treated with 15 kGy. Among the groups, new bone formation was identified in all the groups at each time point. In conclusion, GR at doses of 15 and 25 kGy does not affect the osteoinductive properties of DDM powder. Demineralized dentin matrix (DDM), which is obtained by removing inorganic salts with minimal leaching without denaturing the organic components of the matrix, is defined as an acid-insoluble, highly cross-linked type I collagen with matrix-binding proteins such as bone morphogenetic proteins (BMPs) . Bang anRegarding allogeneic bone substitutes, demineralized bone matrix (DBM) has been widely used in patients with skeletal defects and periodontal diseases . Both DDA variety of allograft processing procedures have aimed to assure virus inactivation using detergents, freeze-drying, chemical sterilization, and gamma irradiation (GR). These have been evaluated and result in an exponential reduction in the potential for graft contamination, disease transfer, or both ,15,16. AAlthough GR provides additional assurance of bone allograft safety from viral transmission, the major disadvantage of GR sterilization is its hazardous effects on the osteoinductivity of DBM ,14. UrisConcerning DDM, because dentin matrix is different from bone matrix since there are no cells and vessels, DDM seems to be safer than DMB in terms of transmissible viral inactivation with similar osteoinductive functions ,8. HowevBased on these previous studies of DBM, which have similar components and functions to DDM, the aim of this study is to investigate the effects of GR sterilization at doses of 15 and 25 kGy on the osteoinductive properties of human DDM in the subcutaneous tissues of nude mice. We hypothesized that GR sterilization of DDM does not hinder the osteoinductivity of DDM.This study was approved by the Institutional Animal Care Committee of Seoul National University Bundang Hospital  (IACUC No. BA-2008-301-070-01). All the experiments were performed in compliance with the Guide for Experimental Animal Research of the Laboratory for Experimental Animal Research, Clinical Research Institute, SNUBH, South Korea, and were confirmed with the provisions of the Declaration of Helsinki.The DDM was purchased from Korea Tooth Bank . It was fabricated according to the standardized procedures of the KTB and the Guidelines of Good Practice for Tooth Handling Institution from the Korea Ministry of Health and Welfare (KMHW) . The conBriefly, the extracted human teeth were soaked in 70% ethyl alcohol, and they were cleaned by removing the soft tissues of the periodontium, pulp, and caries. After dividing the cleaned teeth into the crown and root, the root portion was collected and prepared as DDM. The crushed particles (300–800 μm) were soaked in distilled water and hydrogen dioxide solution and the remaining foreign substances were removed using an ultrasonic cleaner. The cleaned particles were dehydrated with ethyl alcohol and subjected to defatting using ethyl ether solution. The particles were then demineralized for 30 min in 0.6 N HCl. The demineralized particles were lyophilized, packed, and sterilized with ethylene oxide gas.GR was conducted using Greenpia Technology  by a gamma-ray (Co-60) survey facility instrument . The total absorbed dose of gamma radiation was obtained at room temperature at a dose rate of 1 kGy per unit of time. A dosimetry system  was used following the IAEA standards to verify the standardization of the absorbed doses, with a total absorbed dose error of less than 8%.In this study, 20 male athymic nude mice  were purchased from Orientbio©  and were housed in four separate cages with a standard diet and water at the animal laboratory of the Seoul National University Bundang Hospital Animal Research Center. The room temperature was maintained at 22.24 °C, and it was synchronized for a light–dark cycle that was 12 h. All the protocols were carried out according to the Ethical Guidelines of the Animal Protection Association and were approved by the Animal Care and Ethics Committee.®, Kyeongi-do, Korea) for local anesthesia, a 5 mm linear incision was made on both thighs of the mouse, and a subcutaneous dissection was performed to secure the space for the graft. To reduce the number of animals, 30 mg of DDM was grafted into the right subcutaneous pocket of the thigh, and 30 mg of 15 or 25DDM was grafted to the left. In this study, 20 nude mice were equally allocated to Group A  and Group B , respectively  and 2 L/min of oxygen. The site was disinfected with povidone-iodine. After infiltration of 1.8 mL of 2% lidocaine HCl . Following surgery, postoperative care was performed with gentamicin  and ketorolac tromethamine  daily for three days to reduce the pain and prevent infection. The site was disinfected with a povidone-iodine solution for one week.3) was measured in five nude mice in each group using dual-energy X-ray absorptiometry  immediately after the sacrifice through carbon dioxide euthanasia. The X-ray settings were as follows: energy of 50 kV and an intensity of 500 μA. According to the mass in the subcutaneous pocket, a 1 mm × 1 mm square area in the peripheral area was selected as the region of interest (ROI). From this, the parameter of the bone mineral density (BMD) was measured, and then it was compared between the groups.At two and four weeks postoperatively, the bone mineral density  % was calculated as the NB divided by the total bone (TB), which consists of NB and DDM particles (NB % = s × 100) .The normal distribution of all the data was confirmed by the Kolmogorov–Smirnov test and the data were expressed as the mean ± standard deviation. To compare the three grafts , a statistical analysis was performed using single factor analysis of variance  using the software program SPSS version 25.0 e . The significance was set at a level of 0.05.Osteoinduction associated with DDM grafts could be observed in decalcified sections, as shown in Alkaline phosphatase (ALP) is the key enzyme for osteoblast differentiation and bone calcification in osteoblasts. Considering the control samples, positive ALP staining is reddish-brown, while positive TRAP staining is purple . DDM andThese in vivo ALP activities are well-correlated with the above histological findings, determining that representative ALP staining did not show any bone formation activity when exposed to 15 kGy radiation dosage b, while At two weeks, the number of osteoblasts was 5.3 ± 2.1, 5.7 ± 5.5, and 8.1 ± 3.9 in DDM, 15DDM, and 25DDM, respectively. At four weeks, the number of osteoblasts was 7.4 ± 5.4, 6.3 ± 2.5, and 6.9 ± 3.2 in DDM, 15DDM, and 25DDM, respectively. The numbers of osteoblasts are in line with the amount of new bone formation in each group and time point . The numThe amount of new bone formation was 17.8 ± 13.4, 16.8 ± 5.47, and 20.8 ± 10.4% in DDM, 15DDM, and 25DDM, respectively, at two weeks. At four weeks, the amount of new bone formation was 26.1 ± 22.4, 18.0 ± 9.3, and 23.0 ± 7.2% in DDM, 15DDM, and 25DDM, respectively. There was no statistical significance in new bone induction among the groups .3 in DDM, 15DDM, and 25DDM, respectively, at two weeks. At four weeks, the BMD was 0.128, 0.102, and 0.095 g/cm3 in DDM, 15DDM, and 25DDM, respectively. However, there were no statistically significant differences between all groups  . The bioGR may inactivate some growth factors in DBM , but BMPBecause this is the first report on the effect of GR on the osteoinductive properties of DDM, it is only possible to extrapolate the results of this study on the basis of the previous studies on the DBM. Taking into consideration the limitations of this study, DDM with GR might be effectively compared to DBM in terms of an allogeneic osteoinductive bone substitute. However, the exact mechanism of the action of GR on DDM collagen and its growth factors are unknown. The relationship between the most appropriate GR dose for viral clearance and the biological impact on the osteoinductivity of DDM should be further investigated.Regardless of gamma radiation at 15 and 25 kGy, the activity of osteoclast-like cells and osteoblast is confirmed on the DDM, and new bone is induced in the extra-skeletal site. Therefore, this study suggests that gamma radiation at a 15 and 25 kGy dosage does not affect the osteoinduction capacity of DDM. However, the effects of gamma radiation on DDM have to be carefully monitored if it is ever to be used as a method for sterilizing DDM prior to implantation or as part of a bioactive composite because of its potential to inactivate osteoinductive factors.


The top and bottom of the column were analyzed using data from compressive strength, dynamic modulus of elasticity, water penetration, and diffusion coefficients derived from the electrical resistivity test. This article presents the properties of fresh concrete and concrete after two years of setting. It was determined how the different ratios of basalt, magnetite, and serpentinite affect the individual measured parameters. Furthermore, correlation relations between individual resulting values were analyzed. It was observed that compressive strength generally does not correlate with other results. The diffusion coefficient correlated well with density and water penetration. Little or no correlation was observed in the diffusion coefficient with compressive strength and modulus of elasticity. The results of the study make it possible to refine the testing of heavy concretes in terms of electrical resistivity, and point to the possible use of NDT methods. The results also show which composition of heavy concrete is better in terms of effective diffusivity.Radiation-shielding concrete has been analyzed by several methods of destructive and non-destructive testing (NDT). Concretes made of crushed basalt, magnetite, serpentinite, and two different types of cement (Portland cement CEM I and slag cement CEM III/A) were studied. In this study, we analyzed concrete columns with a height of 1200 mm and a cross-section of 200 × 200 mm The use of nuclear energy instead of burning fossil fuels is an ever-expanding process. New nuclear power plants are under construction around the world, and require high-quality building materials . ResearcThe dynamic ,12 and tThe general requirements for the protection of concrete against radiation are high density, low porosity, and good workability . The preDiffusion, and thus resistance to penetration, is also significantly affected by cracks and microcracks ,24, whic3), were chosen as supplementary aggregates. The chemical compositions and properties of types of cement are listed in Our choice of materials for radiation-shielding concrete was based on a published study . The choAnother important factor is the choice of cement. Two types of cement were selected for the study —namely, w/c) was 0.48 for all mixtures except one, where it was 0.60. For this mixture, however, the effective ratio was 0.48. The selection of fractions was first-order governed by ratios of magnetite and serpentinite of 2:1 and 1:2, and was further supplemented so that the sand fully complemented all fractions [The analyzed concrete mixtures also contained a superplasticizer based on polycarboxylate (HRWR) and water . Anotherractions . The goa2 were prepared for the long-term measurement of rheological properties , standard (2000–2600 kg/m3), or heavy (above 2600 kg/m3).The bulk density of concrete was determined in the naturally wet state as the ratio of the weight of a given amount of hardened concrete to its volume. Subsequently, it was possible to determine whether the concretes were light  was used to measure the electrical resistance of the surface. The test was performed on cylindrical samples from the top and bottom parts of columns according to AASHTO T358 standards . The difIt is necessary to note that, in principle, this process is an NDT method. However, in this case, the drilled cores were analyzed. To maintain the principles of NDT, it would be possible to evaluate the surface resistivity directly on the construction of columns without the need for drilling. However, the cores were drilled earlier for other tests.It should be noted that many other properties of the presented concretes have already been published —especialAs shown in 3. On the other hand, concretes C2, C3, and C6, which do contain magnetite 0/16, showed a high density, up to 3600 kg/m3. The type of cement did not affect the result. This is in line with expectations.The first parameter of measurement was density see . The difAnother result was compressive strength see . As addrThe results of the modulus of elasticity showed very similar behaviour in terms of comparison between the mixtures as the compressive strength did see . Here, aThe last—but no less important—result was the apparent diffusion coefficient see . This isThe differences between the top and bottom parts of the columns were insignificant in terms of measurement tolerance. On the other hand, the significance of the differences between the individual concretes was high. Concretes containing mainly 2/16 basalt or serpentinites showed low diffusion coefficient values, while concretes containing magnetite showed high diffusion coefficient values. Of particular interest are the lower values of C6 concrete, which is made of magnetite but contains CEM III/A cement. It is necessary to make clear that in terms of resistance, a low diffusion coefficient is better than a high one. Thus, the evaluation of concretes C2 and C3 shows that they have less resistance than other concretes.The resistance of CEM III/A cement concrete to water penetration in the direction perpendicular to the concreting was higher than that of CEM I cement concrete. The water penetration results are shown in The significant advantage of measuring resistivity is that it is a form of NDT. Because of that, the results of all other tests were compared with the results of the diffusion coefficient with regard to potential relationships. In To supplement the results, correlations between all measured and presented values were also evaluated. The individual parameters were density, compressive strength, modulus of elasticity, and water penetration. By comparing all of them, six pairs were created. The results are shown in No correlation was observed between the individual parameters, except for between density and modulus of elasticity. Interestingly, all values showed an upward trend. The only graph where the trend is declining is between the diffusion coefficient and the compressive strength.Previously, significant differences in the permeability and moisture diffusion coefficients of heavy concretes, depending on the location of the samples, were found . HoweverThe modulus of elasticity was slightly different. The difference between the upper and lower parts was negligible, and concrete containing magnetite was shown to achieve the best results. Conversely, the worst was concrete with serpentinites of all fractions. As stated in a study of high-strength concretes , the evaDiffusion parameters showed significant differences between concretes. It should be emphasized that the values were obtained by measuring the electrical resistance, which is affected by the conductivity properties of the material, porosity, etc. . Therefo1.The best results in almost all tests were shown by C2 concrete, which contains about 30% magnetite 0/5 and about 70% magnetite 0/16. Conversely, in the evaluation of the diffusion coefficient, this concrete was the worst;2.The worst results in almost all tests were shown by C7 concrete, which contains ~20% serpentinite 0/2, ~60% serpentinite 2/8, and ~20% serpentinite 8/16;3.A correlation was observed between the diffusion coefficient and the density, between the diffusion coefficient and the water penetration, and between the density and the modulus of elasticity;4.Evaluation of heavy concretes using electrical resistivity must be further expanded by a larger number of samples and ratios of aggregates in concrete mixtures.This article presented the results of measurements on samples obtained from columns of heavy concrete two years after concreting. These heavy concretes were prepared with the main requirement being radiation resistance. The differences between the top and bottom parts of the columns were evaluated, and the individual results were also compared in order to analyze the similarities. The following conclusions were reached:These results can help to expand knowledge about heavy concretes and their evaluation using destructive and non-destructive methods. Ultrasonic testing and electrical resistivity testing as NDT methods may be suitable for the analysis of existing structures.