Angiogenesis is considered to be one of the key stages in the development of endometriosis. Recent studies indicate that bone morphogenetic proteins (BMPs) and their receptors (BMPR) may play an important role in the angiogenesis process. In the literature, however, there is a lack of publications concerning binding BMPs and their receptors with the pathogenesis of endometriosis. The aim of the study was to determine the role of soluble bone morphogenetic proteins, BMP-2 and BMP-7, and their receptors, ALK-1 and BMPR2, in the process of the formation and development of endometriosis. Peritoneal fluid was collected in the proliferative phase of the menstrual cycle, from 80 women aged 21–49 years (mean age 31.3 ± 6.7 years) undergoing laparoscopy to determine the causes of primary infertility. The study involved 60 women in the I, II, III, and IV stages of the disease. The reference group consisted of 20 women who did not have endometriosis or other lesions in the pelvic area. The concentration in the peritoneal fluid of women with endometriosis was compared to the concentration of this parameter in the reference group, and a statistically significant reduction in the concentration of the BMP-2 molecule was found, as well as increasing concentrations of BMP-7, ALK-1, and BMPR2. BMP-2 and BMP-7 and their soluble receptors, ALK-1 and BMPR2, are involved in the formation of endometriosis. The changes in the concentrations of most of the tested parameters demonstrated in the study, especially in the early stages of the disease, may indicate the more effective formation of new blood vessels in this period. Endometriosis is a chronic inflammatory disease in which the active endometrial tissue of the uterus body occurs ectopically, outside the natural place of its location, mainly within the peritoneal cavity . IrrespeImportant factors involved in angiogenesis, including those regulating the proliferation of vascular endothelial cells, are bone morphogenetic proteins  and their receptors . These factors demonstrate the protective qualities of angiogenesis on endothelial cells against apoptosis, which favor their intensive proliferation and the remodeling of blood vessels, and also create conditions for the formation of a new vascular network . In addiThe presence of bone morphogenetic proteins and their receptors as soluble forms makes it possible to determine their presence in biological fluids, including peritoneal fluid. Due to the fact that studies on the concentration of these parameters in peritoneal fluid among women with endometriosis have not yet been conducted, it is important to elucidate their participation in the formation and development of this disease.The aim of the study is to determine whether selected bone morphogenetic proteins and their soluble receptors are involved in the formation and development of endometriosis.This goal was achieved through the recognition of the concentration value of BMP-2 and BMP-7 bone morphogenetic proteins and their receptors, type-IALK-1 and type-IIBMPR2, in the peritoneal fluid of women with endometriosis, as well as the determination of whether the tested women showed any correlation between the concentration of the examined parameters and the stage of the disease.The study included 80 women aged 21–49 years (mean age 31.3 ± 6.7 years) undergoing laparoscopy to determine the causes of primary infertility. The examined women were patients of the Department and Clinical Ward of Gynaecology and Obstetrics, Professor K. Gibiński University Clinical Centre, Medical University of Silesia in Katowice. The inclusion criteria were as follows: written informed consent to participate in the study, regular menstrual cycles lasting 28 ± 4 days, general good health, diagnosis of primary infertility, no history of the use of hormonal substances for 3 months before laparoscopy, no history of autoimmune diseases, as well as benign or malignant lesions in the ovaries and the uterus. The exclusion criteria were as follows: failure to deliver written consent to participate in the study, irregular menstrual cycles (not lasting 28 ± 4 days), history of immunomodulators, hormonal medication, general poor health, non-malignant or malignant changes in the ovaries or the uterus. In total, 60 women aged 21–49 years (mean age 31.9 ± 7.0 years) were enrolled in the study group; among them, endometriosis in the small pelvis was diagnosed during laparoscopy and then confirmed by histopathological examination. The extent and severity of endometrial changes in the peritoneal cavity were evaluated according to the classification of the American Society of Fertility (rAFS), including the division into stages I, II, III, and IV of endometriosis. In total, 20 women were at the first stage of endometriosis, 16 women at stage II, 15 women at stage III, and 9 women were diagnosed at stage IV. The reference group consisted of 20 women aged 21–46 years , who had no endometriosis or other pathological changes observed in the small pelvis region during laparoscopy. All of the women were informed about the purpose of the research and they expressed their consent for the collection and use of their peritoneal fluid for scientific purposes. Approval was granted by the Bioethics Committee of the Medical University of Silesia in Katowice, No. KNW-6501-57/07, for the tests. The test material was the peritoneal fluid collected during laparoscopy from women in the proliferative phase of the menstrual cycle. Immediately after collection, the peritoneal fluid was centrifuged at 2500 rpm for 10 min at 4 °C, to separate the fluid from the cells. After centrifugation, the supernatant was divided into small portions and stored at −80 °C until the assays were made.-Bone morphogenetic protein 2 ; test sensitivity: 5.5 pg/mL.-Bone morphogenetic protein 7 ; test sensitivity: 14.7 pg/mL.-Soluble type I receptor for bone morphogenetic proteins ; test sensitivity: 0.049 ng/mL.-Soluble type II receptor for bone morphogenetic proteins ; test sensitivity: 0.117 ng/mL.Peritoneal fluid concentrations were determined through the use of Enzyme Linked Immunosorbent Assays (ELISA) by Cloud-Clone Corp., Houston, state, USA for the following parameters:p < 0.0001). The average BMP-2 concentration among women with endometriosis was 0.14 ng/mL (Q1: 0.09 and Q3: 0.18), and in the reference group: 0.36 ng/mL (Q1: 0.46 and Q3: 1.66). The concentration of BMP-2 in the peritoneal fluid of women with subsequent degrees of endometriosis and in the reference group is shown in p < 0.05). In the group of women with stage III endometriosis, the concentration of BMP-2 demonstrated a statistically significant increase compared to the concentration of this parameter in the fluid of women at stage II (p < 0.05). In the fourth stage of endometriosis, the BMP-2 concentration reached the highest value; however, compared to the concentration of this parameter in the peritoneal fluid of women at the third stage of endometriosis, this was not a statistically significant change. In the 4th stage of endometriosis, the BMP-2 concentration reached the highest value, however, comparing to the concentration of this parameter in the peritoneal fluid of women with the 3rd degree of endometriosis, this was not a statistically significant change. There was no statistically significant correlation between BMP-2 concentration and the degree of endometriosis.In the peritoneal fluid of women with endometriosis, BMP-2 concentration decreased, in comparison with the concentration of this parameter in the reference group (p < 0.0001). The average concentration of BMP-7 among women with endometriosis was 0.93 ng/mL (Q1: 0.81 and Q3: 1.46), and in the reference group, this was 0.52 ng/mL (Q1: 0.28 and Q3: 0.59). The concentrations of BMP-7 in the peritoneal fluid of women with subsequent degrees of endometriosis, and in the reference group, are shown in p < 0.0001). A statistically insignificant decrease in BMP-7 concentration was found among women with stage III endometriosis compared to the level of this parameter in the fluid of women at stage II of the disease. A statistically insignificant decrease in BMP-7 was demonstrated among women at stage IV of endometriosis compared to the concentration of this parameter among women at stage III of the disease and a statistically insignificant decrease in BMP-7 was demonstrated among women with stage I of endometriosis comparing to the concentration of this parameter among women with stage IV of the disease. It was observed that, in the fluid of women with stage IV endometriosis, the concentration of BMP-7 was the lowest in comparison to the concentration of this protein among women at stages III, II and I of the disease. A negative and statistically significant relationship between the concentration of BMP-7 in the peritoneal fluid and the stage of endometriosis  was also proven, which is shown in As a result of the tests carried out in the peritoneal fluid of women with endometriosis, a statistically significant increase in BMP-7 concentration was found compared to the concentration of this protein among women from the reference group (p < 0.0001). The average concentration of ALK-1 in women with endometriosis was 1.01 ng/mL (Q1: 0.72 and Q3: 1.75); in the reference group, this was 0.75 ng/mL (Q1: 0.44 and Q3: 0.96). The concentrations of ALK-1 in the peritoneal fluid of women with subsequent degrees of endometriosis and in the reference group are shown in p < 0.0001). A statistically insignificant decrease in BMP-7 concentration was found in women at stage III endometriosis compared to the level of this parameter in the fluid of women at stage II of the disease. A statistically insignificant decrease in BMP-7 concentration was also observed in women at stage IV endometriosis compared to the concentration of this parameter in women at stage III of the disease. It was observed that, in the fluid of women with stage IV endometriosis, the concentration of BMP-7 was the lowest, compared to the concentration of this protein in women at stages III, II, and I of the disease. In addition, it was shown that there is no statistically significant relationship between the concentration of the ALK-1 receptor in peritoneal fluid and the concentration of bone-2 morphogenetic protein in the peritoneal fluid of women with endometriosis. In contrast, a negative statistically significant relationship was observed between the concentrations of ALK-1 receptor in peritoneal fluid and bone morphogenetic protein-7 in women with endometriosis . A linear regression curve illustrating this relationship is shown in As a result of the tests carried out in the peritoneal fluid of women with endometriosis, a statistically significant increase was observed in the concentration of ALK-1 in the peritoneal fluid of women with endometriosis, compared to the concentration of this parameter in the reference group (p < 0.0001). The average concentration of BMPR2 in women with endometriosis was 1.87 ng/mL (Q1: 1.27 and Q3: 4.34), and in the reference group, this was 0.87 ng/mL (Q1: 0.55 and Q3: 1.36). The concentrations of BMPR2 in the peritoneal fluid of women with subsequent degrees of endometriosis and in the reference group are shown in p < 0.0001). It is worth emphasizing that, in women at the first stage of endometriosis, the BMPR2 concentration was the lowest while, in those at the second stage of the disease, the level of the examined receptor reached the highest value. It was also observed that, at the third stage of endometriosis, the concentration of BMPR2 demonstrated a statistically significant decrease compared to the concentration in the fluid of women at the second stage of the disease (p <0.0001). However, in women at the fourth stage of endometriosis, the concentration of the studied parameter decreased compared to the concentration in those at the third stage of endometriosis, and this was not a statistically significant change. It was also shown that there is no statistically significant relationship between the concentration of the BMPR2 receptor and the concentration of bone morphogenetic protein 7 in the peritoneal fluid of women with endometriosis. In addition, no statistically significant correlation was found between the type-II receptor concentration for BMPR2 and the type I receptor concentration for ALK-1. In contrast, a negative statistically significant relationship between BMPR2 receptor concentration and bone morphogenetic protein 2 concentration  is shown in As a result of the tests performed in the peritoneal fluid of women with endometriosis, a statistically significant increase in BMPR2 concentration in the peritoneal fluid of women with endometriosis was found, compared to the concentration of this parameter in the reference group (Current research has shown that, in the ectopic endometrium of women with endometriosis, there is a disorder of intercellular transmission, which involves the BMP-2 signaling molecule. This protein is a signaling pleiotropic molecule and is able to regulate proliferation and differentiate many cell types. Among them are pericytes, which are important structural and functional elements in blood vessels. These cells are responsible for strengthening the structure of the basement membrane of new blood vessels. In contrast, pathological conditions favor the process of tissue fibrosis ,7. The rChanges in the concentration of bone morphogenetic proteins, BMP-2 and BMP-7, and their soluble type-I receptors, demonstrated in the peritoneal fluid of women with endometriosis, ALK-1, and type-IIBMPR, indicate their participation in the pathogenesis of endometriosis, mainly by affecting the process of angiogenesis. In addition, disturbances in the distribution of BMP-2 and BMP-7 molecules can be an important factor in the process of decidualization in women with endometriosis. As a result, this can lead to problems with conceiving and miscarriages for these women.


Regarding the studies analyzed, all of them had scores of >7 on the PEDro and AMSTAR scales. Conclusions: Research on Community Occupational Therapy constitutes a consolidated line of research but the objectives and areas of research were limited. Descriptive qualitative methodology predominated and studies on the effectiveness of Community Occupational Therapy interventions showed a medium–low level of evidence.Background: This review aims to evaluate the level of scientific evidence for the effectiveness of Community Occupational Therapy interventions. Methods: A systematic review was used to analyze and synthesize the studies collected. The databases of Cochrane, OTseeker, OTCATS, Web of Science, Scielo and Scopus were used in order to collect articles published between 2007 and 2020. PRISMA recommendations were followed. Results: A total of 12 articles comprised part of the study . The main areas of practice were geriatric gerontology (22.1%) and mental health (19.7%), which were statistically significant (χ According to the Ottawa Charter, health is a positive concept that underlines the importance of social and personal resources in order to achieve an adequate state of physical, mental and social well-being. The promotion of health is focused on populations or communities in order to create the necessary conditions for them to improve their health or exercise greater control over it ,2.Today, occupational therapists adhere to this perspective, recognizing that health is supported and maintained when individuals are able to engage and participate in occupations and activities at home, school, the workplace and in their community . OccupatThis community perspective of health and its relationship with occupation has given rise to an abundant source of literature in recent years ,5,6 concHowever, a literature review does not allow us to identify studies that rigorously and clearly describe the definition and characteristics of this type of practice. There are also no systematic reviews of the scientific literature that synthesize the scientific evidence regarding Community Occupational Therapy interventions. Accordingly, we believe that a scoping review is fully justified, since it allows us to delimit and describe an area of evidence regarding Community Occupational Therapy interventions. Only in this way can Community Occupational Therapy represent a solid base for occupational therapist practice, thus moving away from isolated interventions that blur its nature, ignoring the emerging reality that makes it such .Therefore, the research questions guiding this review were: (a) What was the volume, content and characteristics of the research carried out on Community Occupational Therapy? (b) What level of scientific evidence did the analysis of the scientific literature provide on the efficacy of Community Occupational Therapy?A scoping review method was used to conduct an exploratory mapping of occupational therapy research at the community level. This type of methodology was selected because it allows the examination of a heterogeneous body of knowledge, both in terms of disciplines and research methods ,18. In tFirst, the research questions were identified based on a preliminary review of the literature. In addition, the MESH terms and keywords of the search were selected in order to identify all available included and/or accessible studies on occupational therapy in the community setting.Second, a search strategy was carried out using six databases  with an initial result that located 6453 articles. The MESH terms and keywords used were: “occupational therapy”, “community based”, “community service”, “community-based”, “community health”, “community development”, “community”, and “community-based rehabilitation”. The search was carried out between 1 January 2007 and 1 December 2020 by targeting the MESH terms and keywords in the title, abstract, keywords and main text. The strategy of the search used for Web of Science that was subsequently adjusted to the rest of the databases was: (“Community-Based”) OR (“Community Based”) OR (“Community Service”) OR (“Community Based Rehabilitation”) OR (“Community”) OR (“Community Development”) OR  AND . These were refined by: (Excluding) Types of documents: .n = 3753 duplicated articles. The following selection criteria were established as inclusion criteria: (a) any study of a quantitative or qualitative nature that looked at occupational therapy in the community setting, (b) all age ranges, (c) studies published in English, Spanish, Portuguese, French and Catalan, (d) any type of population, scope of practice and/or health condition. The exclusion criteria were: those that did not have occupational therapy interventions in the community setting as the main objective of the study. Subsequently, the eligibility process was based on the synthesis of 122 articles.Third, the screening process was performed by ordering the references using the Mendeley manager (version 1.5.2), eliminating Fourth, two authors of the study independently performed a complete reading of the 122 selected articles by extracting the data from each article in an Excel table (v.11) prepared by the research team, which recorded the following information from each study: author(s), year of publication, journal, study methodology and design, scope of practice, study objectives or research question, sample, intervention, evaluation tools used in the study, statistical analysis and outcome measurements, limitations and conclusions. Subsequently, a third author independently reviewed the analysis of the extracted data. Any differences in the analysis of the documents between the different authors were resolved by consensus between them. Based on data extracted from the 122 selected articles, the first research question: (a) What was the volume, content and characteristics of the research carried out on Community Occupational Therapy? was answered.Fifth, the strategy included 40 studies that represented a quantitative synthesis. Furthermore, in order to calculate the level of scientific evidence in the 40 studies, we used the SING scale . With th2) test was applied in order to verify the null hypothesis of equality of proportions, using a confidence interval of 95%. This analysis made it possible to identify the volume, content and characteristics of the research and to summarize the existing scientific evidence on occupational therapy interventions in the community setting [Finally, a descriptive and inferential statistical analysis of the variables recorded in the study was carried out using IBM SPSS Statistics version 19) and EPIDAT 3.1. The quantitative variables were expressed by using the mean, frequency and percentage. In the inferential analysis, the Chi-square (χ and EPIDThe search identified 122 relevant documents after a full-text review .n = 15 (12.3%); American Journal of Occupational Therapy n = 13 (10.7%) and the Scandinavian Journal of Occupational Therapy n = 10 (8.2%). The rest of the journals published less than ten articles that were relevant to the research questions between 2007 and 2020. As shown in The 122 articles included in the synthesis were published in 49 indexed journals, primarily in English. They were predominantly publications in occupational therapy journals: Australian Occupational Therapy Journal n = 40 (32.8%), Australia n = 25 (20.5%), Canada n = 24 (19.7%) and England n = 10 (8.2%). The rest of the countries had less than ten published articles. Only one study was found in Spanish Puerto Rico n = 1 (0.8%) and one in Portuguese Brazil n = 1 (0.8%).The countries that produced the most literature on the objectives of the study were: USA n = 27 (22.1%), mental health n = 24 (19.7%), and physical dysfunction . In the rest, the percentage number of studies was less than 6%. In the areas of geriatrics and gerontology, and mental health, a statistically significant difference was identified  when compared to the rest of the practice areas. Regarding the research objectives, those related to the assessment of evaluation tools and the application of practice models n = 18 (14.8%), the evaluation of intervention programs to improve health n = 12 (9.8%), and the evaluation of leisure interventions and/or social participation in the community n = 12 (9.8%), were the most frequent. The average duration of the intervention programs evaluated was 2.5 months, and the rest of the research objectives were less than 9.8%.The practice areas with the greatest number of investigations were: geriatrics and gerontology 2; p < 0.005) was identified. A total of 58.2% of the studies used a qualitative design: 20(16.4%) phenomenological, 18 (14.8%) participatory action research (PAR), 15 (12.3%) ethnographic, 12 (9.8%) narrative, and 6 (4.9%) meta-ethnographies. A total of 32.7% of the studies used a quantitative design: 7 (5.7%) RCT, 7 (5.7%) systematic reviews, 1 (0.8%) meta-analysis, 3 (2.5%) pilot studies, 7 (5.7%) case–control studies and 15 (12.3%) cohort studies.Qualitative research predominated in the study. When compared with the rest of the methodological strategies, a statistically significant difference . In addition, the main objective of a quarter of the research in these areas focused on the evaluation of the effectiveness of different intervention programs. In geriatrics, such programs had the main objectives of improving the functionality and quality of life, reducing the risk of falls and overloading caregivers, increasing autonomy in the performance of activities of daily living and independence in the home, and promoting the health and well-being of healthy older people residing in the community.In the case of mental health, the main objective of intervention programs is to improve the performance of basic activities of daily life, provide independence in the community, social participation, quality of life, mood and general health, as well as reducing addiction relapse and caregiver burden. However, the average duration of such programs was short, with an average of 2.5 months, which considering the objectives, is usually achievable in the medium- or long-term once such programs are established . In addiTherefore, in light of the results of this study, we advocate increased research on health promotion and prevention of disability in the community, with the aim of expanding the scientific evidence on the efficacy of Community Occupational Therapy related to these spheres.Regarding the methodological characteristics of the research, on the one hand, we considered that the range of research objectives was limited. This circumstance could be related to the meagre experience and poor tradition of the practice of Community Occupational Therapy, which implies a significant lack of tools and intervention strategies, as well as the necessary skills for the implementation of distinctive actions and proven effectiveness ,41. In tOn the other hand, it should be noted that the qualitative methodology of a descriptive nature predominated, since the percentage of quantitative studies (32.79%) was significantly lower than the percentage of qualitative studies (58.20%). This fact could be related to the suitability of this methodology, in relation to the objectives usually proposed in Community Occupational Therapy studies, which seek to apprehend the subjective experience of the health of members of the community. Considering the data obtained in this review, it appeared that research on Community Occupational Therapy has reached a period of consolidation, adopting a variety of both qualitative and quantitative approaches, although qualitative studies still predominated. However, we believe that it would be advisable to increase quantitative research in order to provide scientific evidence ,45,46.Nevertheless, it should also be noted that, according to the data analyzed in this scoping review, some of the studies identified had low methodological quality. Therefore, we consider it necessary to improve such quality. These findings seemed to indicate the need to improve the quality of evidence from the effects of Community Occupational Therapy programs in specific areas, in order to reduce the variability of the practice and improve its efficacy ,48. It sRegarding the second question of this review, despite the fact that in recent years there has been a significant increase in evidence-based research as a fundamental basis for the best choice of occupational therapy practice in the community, the quality of evidence of efficacy for this practice is inconclusive or sparse. A high percentage of studies based on the efficacy of Community Occupational Therapy interventions showed a medium–low level of evidence. Therefore, not all the scientific studies analyzed had the same value with regard to decision making in choosing the best available practice. In fact, studies classified as 1- and 2- should not be used in the recommendation-making process due to their high potential for bias. However, it should be considered that the studies included were too small to detect this effect. It is possible that methodological limitations and the heterogeneity of the studies included meant that the effect was not detected.In this same sense, it should be noted that, in the field of mental health, despite the high percentage of studies identified in the review, no randomized controlled studies, meta-analyses or systematic reviews have been carried out. Therefore, the scientific evidence gathered regarding the efficacy of occupational therapy interventions in this setting is sparse.Along the same lines, due to the analysis carried out in this scoping review, we should consider the apparent contradiction between the characteristics of interventions considered as Community Occupational Therapy and the definition of this area in the specialized literature on occupational therapy.In recent years, occupational therapy has suggested a profound transformation of the perspective toward the concept of health that changes from the individual to the community ,54,55, wHowever, the results of this review show that scientific research on Community Occupational Therapy focuses on specific groups , with time-limited interventions, which are fundamentally based on an individual concept of health. This circumstance could be related to the absence of a clear and precise definition of the notion and scope of Community Occupational Therapy .From our point of view, the absence of this precise definition, as well as the health exegesis that accompanies it, can lead to the practice of Community Occupational Therapy based on short-term interventions, centered on individuals residing “within” the community, as the results of this scoping review seemed to show.Therefore, we advocate for the practice of Community Occupational Therapy that implies a profound change in the intervention perspective, based on occupational justice and empowerment, which requires medium- and long-term interventions “in, with and from” the community. In other words, Community Occupational Therapy should understand the community as a unit of analysis and independent intervention ,59. OnlyIn short, we defend a greater precision and clarity in the definition of the notion of Community Occupational Therapy, the ultimate support for a real change in the practice of our profession in this area.A detailed analysis of the methods used to assess the risk of bias in the studies included in this review was beyond the scope of this study. Therefore, the absence of this information can be considered as a limitation of the study.Improving the methodological quality of research in this area is a basic recommendation for increasing the scientific evidence on the efficacy of Community Occupational Therapy interventions ,51.It is advisable to develop research projects that allow scientific evidence to be gathered on the efficacy of Community Occupational Therapy interventions in the field of mental health.The efficacy of occupational therapy practice in the community is not entirely clear, but these interventions appear promising and deserve further investigation. The quality of evidence on the effects of Community Occupational Therapy programs is inconclusive or sparse. The Community Occupational Therapy interventions to reduce the risk of falls and enhance the performance of activities of daily life in older people seem to be the most effective strategies. Research on Community Occupational Therapy must heighten the methodological quality of research in order to reduce the variability of the practice and improve its efficacy.


The similar improvement in depressive symptoms observed in both groups was attributed to placebo effect and interaction between participants and research group and not to tDCS intervention per se. In our study, tDCS was safe and well tolerated, but it was not effective in reducing depressive or anxiety symptoms in patients with temporal lobe epilepsy.We conducted a double-blind randomized clinical trial in order to examine the effects and the safety of home-based transcranial direct current stimulation (tDCS) on depressive and anxious symptoms of patients with temporal lobe epilepsy (TLE). We evaluated 26 adults with TLE and depressive symptoms randomized into two different groups: active tDCS (tDCSa) and Sham (tDCSs). The patients were first submitted to 20 sessions of tDCS for 20 min daily, 5 days a week for 4 weeks and then received a maintenance tDCS application in the research laboratory once a week for 3 weeks. The intensity of the current was 2 mA, applied bilaterally over the dorsolateral prefrontal cortex, with the anode positioned on the left side and the cathode on the right side. Participants were evaluated on days 1, 15, 30, and 60 of the study using the Beck Depression Inventory II (BDI). A follow-up evaluation was performed 1 year after the end of treatment. They were also evaluated for quality of life and for anxious symptoms as secondary outcomes. The groups did not differ in clinical, socioeconomic or psychometric characteristics at the initial assessment. There was no statistically significant difference between groups regarding reported adverse effects, seizure frequency or dropouts. On average, between the 1st and 60th day, the BDI score decreased by 43.93% in the active group and by 44.67% in the Sham group (ΔBDIfinal – initial = −12.54 vs. −12.20, Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03871842]. Temporal lobe epilepsy (TLE) is one of the most frequent forms of focal epilepsy and is associated with high rates of neuropsychiatric disorders . DepressTranscranial Direct Current Stimulation (tDCS) has been studied as a complementary and safe therapeutic option for the treatment of psychiatric disorders in PWE . There iSome studies on tDCS in the treatment of depressive disorder and anxiety have used the anodal stimulation protocol over the left DLPFC, with the cathode electrode positioned over the right DLPFC, with 2mA intensity, for 20 to 30 min a day for 5 to 30 days . HoweverConsidering that a longer treatment time can produce better results in depressive and anxiety symptoms  and thatThis study aim to contribute to a better understanding of the potential of tDCS in patients with epilepsy and eventually assist in the development of new treatment protocols for depressive and anxiety disorders in patients with TLE.The present study was conducted in accordance with the World Medical Association’s code of ethics, the Declaration of Helsinki and the rules established by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre, under the Institutional Review Board CAAE 83801517100005327. All participants signed an informed consent form, which describes that participants will be allocated to a sham or active stimulation group, it describes also the mechanism of action of the tDCS as well as its possible benefits, possible side effects and contraindications.The clinical trial was carried out at the Hospital de Clínicas de Porto Alegre epilepsy clinic between January 2019 and March 2020, involving a group of 26 adults (>18 years-old) diagnosed with TLE according to the International League Againt Epilepsy (ILAE) classification for epileptic seizures and syndromes. All patients had depressive symptoms as evaluated by the Structured Clinical Interview for DSM-4 (≥ 4 points in the BDI) and were able to adequately answer the questionnaires and to be able to undergo the treatment. Exclusion criteria were: (1) failure to give informed consent; (2) change in the antiepileptic drug regimen (AED) or in the antidepressant medication regimen 30 days before or during the study; (3) history of status epilepticus in the previous year; (4) being submitted to vagus nerve stimulation, deep brain stimulation or any other type of neurostimulation less than 1 year before this study; (5) active suicidal ideation; (6) contraindication for tDCS, including presence of any metal on the head or any implanted electrical medical device such as pacemakers and cardiac defibrillators, and (7) pregnancy. To ensure adequate adherence, correct use of the device and adequate responses to the questionnaires, we only included patients with normal I.Q. and that we considered that would understand the study.One of the few studies on tDCS for the treatment of depressive symptoms in PWE was conducted on patients with mild or minimal depressive symptoms, obtaining a very small improvement of these symptoms when applying the tDCS for 5 days  . Hence, The sample size was calculated using the WinPepi program to detect differences in mean BDI score over time, between the tDCS Active and Sham groups. Considering 80% power, a 5% level of significance, an expected difference of 9 points for the active tDCS group, and a standard deviation of 7.1 points for the active group and of 7.9 points for the Sham group , the samConsidering that this was a parallel study, the participants were stratified according to the laterality of their epilepsy crises  and were then randomized into blocks of 4 using appropriate software and respecting the 1:1 allocation ratio. The only researcher who had access to the randomization list was the biomedical engineer responsible for configuring the tDCS equipment to active or Sham. All researchers involved in conducting the interviews, contacting the participants and analyzing the data, as well as all included participants were blinded to the allocation. To ensure the participant’s blinding, Sham pacing was programmed to provide 30 s of progressive pacing (15 s 0–2 mA and 15 s 2–0 mA) at the beginning, middle and end of the application to promote the tactile effects of electric current. At the end of the study, we asked the participants what type of stimulation they believed to have received and what was their confidence in the response using a Likert scale from 1 (without confidence) to 5 .We developed a 2-month treatment protocol. The number of tDCS sessions was chosen based on previous articles  and was 2 electrodes coated with a vegetable sponge moistened with saline solution before the start of stimulation by 2 silicone cannulas attached to the electrode. A medical engineer prepared the device for a fixed number of stimulations, with a minimum 16-h safety interval between 2 consecutive sessions.The current was supplied with 35 cm1.We chose the home-based tDCS for home use, whose characteristics are specified in an article by Whatsapp), video and telephone calls during treatment. However, the supervision was not standardized, did not have a pre-established number of remote meeting. It was available if requested by the participant. The information stored on the device, such as number of sessions performed, impedance and duration of the sessions, was recorded by an engineer not involved in the treatment of the participants. The engineer kept these data in his care until the end of the study. Details about the representation of the study procedures over time are shown in Patients were evaluated on days 1, 15, 30, and 60 of the study. A follow-up evaluation was also performed approximately 1 year after the end of treatment. To assess the frequency of seizures, the participants reported the number of seizures during the last month before the beginning of treatment and kept a seizure diary from the first to the 60th day of the study. In the second assessment (day 30), the participants returned the equipment they had received on the first day of the study . All proThe main outcome of this study was the score of depressive symptoms obtained with the Beck Depression Inventory II (BDI), one of the best self-report measures of depression, widely used in clinical research and validated for Brazil . The BDITo assess the impact of treatment on patients’ quality of life, we used the Inventory for Quality of Life in Epilepsy (QOLIE-31) . The 31 Anxious symptoms were assessed using the Hamilton Anxiety Scale (HAM-A) . HAM-A wAll analyses were performed using the IBM Statistical Analysis Software Package (SPSS), Version 20, with bilateral significance tests, at the 5% level of significance. The analyses were performed with the intention of treating. Only one participant had a baseline BDI score higher than ± 2.5 standard deviations (SD) of the group average. This outlier was not excluded. It didn’t affect the calculation of the results.post hoc analysis.We compared the demographic, clinical and neuropsychological characteristics of the groups at the beginning of the study using the t test for continuous variables and the Chi-square test or Fisher’s exact test for categorical variables. Continuous variables were tested for normal distribution using the Shapiro-Wilk normality test. For asymmetric distributions, the groups were compared by the Wilcoxon-Mann-Whitney test. To analyze the psychometric results (BDI and QOLIE-31), we generated a model of Generalized Estimating Equations (GEE) with a dependent variable , and within-subject variable (time), a variable between subjects (active × Sham tDCS) and control for covariates , occupation and income). Bonferroni correction was used for In order to control the covariates, correlation analysis and multivariate analysis of covariance were performed between the following variables: deltaBDI , deltaQOLIE-31  and deltaHAM-A  vs. type of stimulation, age, sex, education, AED, DAD, occupation and income.Of the 120 patients with TLE evaluated for participation in this study at the Hospital de Clínicas de Porto Alegre epilepsy clinic between February 2019 and March 2020, 35 met the inclusion and exclusion criteria. Of these, 26 agreed to participate in the study, being randomized into two symmetrical groups. In the blinding validation questionnaire, two subjects from the Sham group and one from the active group believed they had received a placebo treatment. All other participants believed they have received active intervention. In the active group, one participant dropped out of the trial due to burning discomfort and pain in the scalp produced by the equipment. In the Sham group, one participant left the trial due to loss of interest, and another participant needed to travel. There was no statistically significant difference between groups regarding dropouts from the study. No participant was excluded from the final data analysis. There was no statistically significant difference between groups regarding clinical, sociodemographic, psychometric characteristics and drug uses in the first assessment (pre-treatment) –3.p = 0.3)  (The tDCS did not increase the frequency of seizures during the month of home treatment in relation to the frequency of seizures during the month prior to treatment (p = 0.3) . Regardip = 0.3)  such as = 0.193) . In the = 0.193) . Data sup < 0.001), but not of the interaction time vs. type of stimulation (p = 0.93) or the type of stimulation factor alone (p = 0.42). Regarding the evaluation performed 1 year after the end of treatment, the tDCSs group showed an increase of 4.19 points on the BDI-II scale (from 15.11 to 19.30 points), while the tDCSa group increased on average only 1 point (from 16 to 17 points) . At the end of the third assessment, the initial BDI score decreased 35,0% in the active group and 45,99% in the sham group. In the fourth assessment, this initial BDI score decreased by 43.93% vs. 44.67% in the active vs. Sham groups, respectively , with the participants being reclassified, on average, as having minimal or mild depressive symptoms. Generalized Estimating Equations (GEE) factor analysis showed that there was an influence of the time factor on this improvement ( points) . There wp = 0.003, GEE analysis), with no statistically significant influence of the type of treatment on this improvement (p = 0.9), of the interaction between the time and the factor or the type of stimulation received (p = 0.92). The increase in the score of the QOLIE-31 questionnaire in the active and Sham groups was ΔQOLIE31iii-i = 25.51% vs. 20.91%, respectively. Data about the mean QOLIE31 mean points in each evaluation are available in Likewise, the quality of life of the participants improved over time in both groups (p = 0.05), but not of the time*type of stimulation interaction (p = 0.09) or the type of stimulation factor alone (p = 0.86). There was no statistically significant difference between groups. Analysis of the effect of the type of treatment over time on the BDI variation, with control for the covariables age, sex, education, AED, DAD, occupational situation and income, revealed no statistically significant change in the results.Anxious symptoms were evaluated in three stages on days 1, 30 and 60, using the score obtained with the HAM-A questionnaire. In relation to the initial assessment, the last anxiety assessment showed a reduction of 2.34 points (from 23.23 ± 8.36 to 20.89 ± 10.24) or 10.07% in the tDCSa group, and a reduction of 5.14 points in the tDCSs group (from 22.92 ± 4.28 to 17.78 ± 6.14), representing a reduction of 22.42% . The GEEIn this study, we proposed the application of 20 daily sessions of tDCS at home followed by 3 weekly sessions at the research center in order to reduce depressive and anxious symptoms and to improve the quality of life of patients with PWE. The anode was positioned over the left DLPFC and the cathode over the right DLPFC .Participants in the active tDCS group reported more moderate and severe local adverse effects than participants who received Sham stimulation, although the difference between groups was non-significant. Only 3 participants dropped out of the study (1 from the Sham group and 2 from the active group). On average, both groups performed 13 effective stimulations at home  and 2 of 3 sessions in the laboratory, reflecting limitations in adherence to the proposed protocol.Some of the reasons why patients with epilepsy do not adhere to the self-administered tDCS treatment may be accidental, due to forgetfulness or uncertainty about the doctor’s recommendations, or may be intentional, due to local adverse effects or due to their own treatment expectations . Remote There were two possible points of concern about the safety of applying this bimodal protocol to the sample studied: (i) 76.9% of the participants in active group had at least one crisis in the last year (uncontrolled epilepsy); (ii) many patients had an epileptogenic focus on the left brain hemisphere, where the anodal (excitatory) stimulation was performed. Nevertheless, the program of approximately 15 sessions was safe for the sample studied. There was no statistically significant difference in the frequency of seizures before and after the beginning of treatment in either group. One participant had 1 epilepsy crisis during the 30 days prior to the study, 1 epilepsy crisis during the 30 days of home treatment and 6 epilepsy crisis during the 30 and 60 days of the study, but it is not possible to establish a direct relationship with the stimulation performed considering that the other participants showed no increase in the frequency of epilepsy crisis.Regarding quality of life and depressive and anxious symptoms, even controlling for confounding or interaction variables, both groups showed a similar improvement in symptoms over time, but not due to the influence of the type of treatment. From a pharmacological point of view, antiepileptic drugs, including sodium or calcium channel blockers, and medications that influence neurotransmitters such as GABA, may impact the aftereffects of tDCS . AnotherOne possible explanation for the similarity of response between the two groups is the high significance of the placebo effect in studies on treatment of depression and anxiety . The plaIn the thesis “Placebo’s Feats and Effects,” Saretta highlights the differentiation between “illness” and “disease” as a fundamental criterion for the understanding of the placebo phenomenon in clinical trials . AccordiIn a review article about the needs, perspectives and perceptions of PWE regarding the Health Care System, Muller & Gomes have shown that there are important financial, social, and relationship problems in this population. With regard to social adjustment, difficulty in interpersonal relationships was relatively common; 42% of patients reported having only few or no friends, 27% of female patients considered their crises to be responsible for the difficulties of family life, 40% of the patients reported that they did not have an affective relationship, and 45% reported having difficulty in establishing this type of relationship. Due to the disease itself, 10% of patients reported being involved in legal disputes . The dif(Whatsapp) during the intervention period, interviews about psychosocial content and application of a physical intervention (tDCS) may act as a social intervention and can explain in part the clinical improvement observed in both groups. Around the world, many types of social and educational interventions are being developed as effective interventions for the improvement of psychiatric disorders and quality of life . The patients/participants provided their written informed consent to participate in this study.SM, WC, and MB: conception and design of the work. LA, PR, CT, JB, and PS: acquisition of data. SM, LA, WC, RB, TS, and MB: analysis and interpretation of data. SM, LA, WC, and MB: drafting the work. SM, LA, PR, CT, JB, RB, TS, PS, WC, and MB: revising the manuscript final approval of the version to be published. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The alkali-silica reaction (ASR) is an important consideration in ensuring the long-term durability of concrete materials, especially for those containing reactive aggregates. Although fly ash (FA) has proven to be useful in preventing ASR expansion, the filler effect and the effect of FA fineness on ASR expansion are not well defined in the present literature. Hence, this study aimed to examine the effects of the filler and fineness of FA on ASR mortar expansion. FAs with two different finenesses were used to substitute ordinary Portland cement (OPC) at 20% by weight of binder. River sand (RS) with the same fineness as the FA was also used to replace OPC at the same rate as FA. The replacement of OPC with RS  was carried out to observe the filler effect of FA on ASR. The results showed that FA and RS provided lower ASR expansions compared with the control mortar. Fine and coarse fly ashes in this study had almost the same effectiveness in mitigating the ASR expansion of the mortars. For the filler effect, smaller particles of RS had more influence on the ASR reduction than RS with coarser particles. A significant mitigation of the ASR expansion was obtained by decreasing the OPC content in the mortar mixture through its partial substitution with FA and RS. Fly ash (FA) is one of main by-products from coal combustion in thermal power plants. Currently, the Mae Moh power plant in Thailand produces about 2.1 million tons of fly ash, increasing annually. Fly ash (FA) is also a well-known mineral admixture and has been widely accepted for use as a pozzolanic material to partially replace ordinary Portland cement (OPC) in concrete. The use of fly ash as a pozzolanic material is constantly increasing because it improves the properties of mortar and concrete, namely the workability, durability, and strength in the long term. Generally, fly ash from pulverized combustion has a spherical particle shape and high fineness. However, some fly ashes also contain irregular or angular particles. The size and shape of fly ash particles vary depending on the source and combustion conditions. The chemical composition of fly ash also depends on the characteristics of the coal and burning condition. FA has been studied for a long time and has been continuously developed to improve many of the properties of concrete. In 2010, Sharma et al. ,4,5. MorIn terms of durability, the replacement of 20 to 50% of OPC with FA (by weight of binder) has been shown to produce concrete with lower water permeability than concrete without FA. In addition, similar FA contents have been used to produce concrete with a higher resistance to sodium and magnesium sulfates than OPC concrete . FA is aTurk et al.  confirmeAlthough FA has been proven by many researchers to be a useful pozzolanic material for preventing ASR expansion, the primary reduction of the expansion may be due to other factors, such as the filler effect or the reduction of the OPC content in the mixture. Additionally, the filler effect and the effects of FA fineness on ASR expansion have not been well defined in the present literature. Therefore, this investigation was aimed at examining the influence of the replacement of OPC with FA with different levels of fineness on the ASR expansion of mortar. Two fineness levels of FA were also considered in order to observe the effect of fineness on ASR expansion. Ground river sand (RS) with the same fineness as FA was used to replace OPC at the same rates of FA to study the filler effects of FA and RS on the ASR expansion of mortar.Alkali-silica reaction (ASR) is a dangerous phenomenon in concrete structures, because ASR builds internal pressure causing the concrete to crack. After that, the concrete structure losses its compressive strength and durability, making it easy for moisture and other chemical solutions to migrate into the internal concrete, and leading to the corrosion of steel in reinforced concrete structures. Although, the replacement of OPC by fly ash can reduce the expansion due to ASR, other factors are still not clear, such as the filler effect and the effects of the fineness of the materials. Therefore, the knowledge obtained from this study will help the civil engineer to understand the factors affecting the ASR expansion of mortar, and lead to applying this knowledge in concrete structures in order to obtain the safety and sustainability of structures.A low alkali cement obtained from a cement manufacturer in Thailand, which was classified as type I according to ASTM C150 , was use2), calcium carbonate (CaCO3), and mullite (3Al2O3·2SiO2), while the 5RS had mainly crystals of quartz. However, the quartz in RS does not react with Ca(OH)2 and was treated as an inert material, since the area under the XRD graph was very low. The XRD results of 33FA and 33RS were not analyzed because the results of 33FA and 33RS were assumed to be similar to those of 5FA and 5RS, respectively. Chindaprasirt et al. [After completing the grinding processes, the crystallinity of the 5FA and 5RS were analyzed by X-ray diffraction (XRD), and the results are presented in t et al.  and Kroet et al.  proved t2 + Al2O3 + Fe2O3 is more than 50%, SO3 is less than 5%, and loss on ignition is less than 6%, while the alkali equivalent (Na2Oeq) is 2.8% by weight. The major oxide of 5RS is SiO2, which makes up 92.5% of its content, and the rest are other oxides. The chemical compositions of the materials are given in Many prior studies have established that the fineness of pozzolanic materials has little influence on their chemical compositions . The cheFor mortars containing an ASR reactive aggregate, the coarse reactive aggregate was ground and sieved until the gradation met the requirements of ASTM C1567  for ASR The ASR of the mortar was investigated by an accelerated method, and according to ASTM C1567 . For the3. Mortar bars were de-molded after 24 h of casting and were then cured in tap water at a temperature of 80 °C. The initial length of the mortar was measured 24 h after completion of the previous process. Next, the mortar bars were immersed in a 1 N sodium hydroxide (NaOH) solution at the temperature of 80 °C. The length of mortar bars was read for 28 days and the reading at each time was targeted to be the nearest 0.001% of the nominal gauge length. The reported ASR expansion was presented as the percent change in length, which was obtained from the average of three mortar specimens. The acceptable range of test results between samples at the same testing age and mix proportion was 8.3% of the average as specified by ASTM C1567 [Next, two stainless steel gauge studs were cast-in at both ends of the mortar bar mold for use as an indicator in the measuring process. A mortar mixture was filled and compacted in three molds with dimensions of 25 × 25 × 285 mmTM C1567 .eR is the reduction of the expansion of mortar (%), tE is the average length of mortar bars containing fly ash or ground river sand (%), and ctE is the average length of the control mortar bars (%).The effectiveness of using fly ash or ground river sand in controlling the ASR expansion of mortars was determined according to Equation (1), given by ASTM C441  as follo2 promotes a high yield of ASR product. Additionally, Hou et al. [2, thereby reducing the degree of ASR expansion.As shown in u et al.  demonstru et al. . HoweverThe ASR expansions of mortars containing 5FA and 33FA is presented in 2 (from the cement hydration reaction) leads to a decreased pH in the pore solution. Lindgård et al. [2 pozzolans are the most critical factors in reducing the alkalinity of pore solutions. The corresponding reduction in the concentration of hydroxyl ions in the pore solutions could prevent ASR expansion or reduce its degree. Conversely, the FA used in the current study had a high amount of CaO (25.2 wt.%) and a low amount of SiO2 (33.2 wt.%), but it also reduced the expansions of the mortars. Topçu et al. [2 content in the hardened paste. Moreover, it also decreases the availability of alkali reactants, due to the partial consumption of Ca(OH)2 by pozzolanic reaction [2O3 content might also have an important influence on the alkali capacity of an SCM binder.A mechanism for the reduction of the ASR expansion due the addition of pozzolan was described by Topçu et al. , who read et al.  stated tu et al.  explainereaction ,33,34,35reaction  suggesteThe reduction of ASR expansion in mortar or concrete containing FA is attributed to the reduction of alkali in the binder. However, the main factor that limits the ASR expansion is the lower amount of OPC in the mixture, achieved by using FA as a partial substitute for OPC. To verify this claim, RS  was used to replace OPC instead of FA, to demonstrate the effect of the cement content on ASR expansion.The replacement of OPC with 5RS (high fineness) reduced the ASR expansion of the mortar more than replacement with 33RS (low fineness), because the 5RS particles could better fill voids and resist the penetration of the 1 N NaOH solution into the mortar. For instance, the 5RS mortar had an ASR expansion of 0.061 ± 0.003% at 14 days, while that of the 33RS mortar was 0.112 ± 0.009%. The fineness of RS is one significant factor that influences the reduction of ASR in mortar. Finer RS also provided a higher compressive strength to the mortar than RS with lower fineness, largely due to the filler effect .Although the replacement of OPC by RS can reduce ASR expansion, it can also result in a lower compressive strength of mortar ,38,39. TFillerF is the filler effect of RS on the ASR expansion of the mortar (%), RSE is the ASR expansion of the RS-containing mortars (%), and CTE is the ASR expansion of the CT mortar (%).The filler effect of finer particles improves the mechanical and durability properties of mortar or concrete. Since 33RS and 5RS were ground river sands and consisted mainly of quartz, which does not react with OPC hydration products, the different reductions of expansion between 33RS and 5RS mortars were considered to be predominantly due to the filler effect of the RS material.2 available to react with SiO2 in the reactive aggregate, and there was thus a lower content of ASR products. Moreover, Ca(OH)2 continually reacted with SiO2 in the reactive aggregate, and the filler effect could be observed clearly after 5 days of immersion, with more apparent results after longer immersion durations.The filler effect due to RS was an important factor in lowering the ASR expansion, and the filler effect had a higher degree of effectiveness at a later age. For instance, 5RS exhibited changes in the ASR mortar expansions of −0.177 and −0.283% at ages of 14 and 28 days, respectively, due to the filler effect. It should be noted that the negative values of the expansion indicate that there was a reduction of the ASR mortar expansion compared to the CT mortar. The reduction of the OPC content from 100 to 80% by weight meant there was a lower amount of Ca(OH)When the OPC comprised only 80%, the ASR expansion of the mortars incorporating 5RS and 33RS  was 0.177 and 0.122%, respectively, which were lower than the ASR expansion of the CT mortar. Meanwhile, increasing the fineness of RS, from 33RS to 5RS, produced an absolute increase in the ASR expansion of about 0.055% at 14 days, and 0.092% at 28 days. It is noted that the filler effect of RS (33RS and 5RS) was less effective than the 20% reduction of OPC in the binder, since the lowering of OPC in the mortar by 20% reduced the ASR expansion to about 0.122% (when using 33RS as a replacement for OPC) or 0.177% (when using 5RS as a replacement for OPC), while the reduction of the ASR expansion by the filler effect of 33RS and 5RS was only 0.055% at 14 days.The effectiveness of FA in controlling expansion due to ASR depended on the amount of FA used to substitute OPC. It was observed in previous research  that theThe use of 5RS and 33RS to replace 20% of the OPC reduced the ASR expansion of mortars at 14 days by 76 and 52%, respectively. The use of 33FA and 33RS provided similar reductions in the ASR expansion of the mortar, while the use of 5RS was more effective than the use of 5FA for the reduction of the ASR expansion. However, the replacement of OPC with RS resulted in a lower compressive strength of the mortars, compared to those with FA. Mortars containing 20% of 5RS and 33RS had a strength activity index of 89% and 78%, respectively, at the age of 28 days. In contrast, the mortars containing 20% of 5FA and 33FA had a strength activity index of 108 and 93%, respectively, at the age of 28 days .The use of FA with 5 and 33 wt.% of its particles retained on a No. 325 sieve to replace 20% of OPC reduced the ASR expansion of the mortar. The extent of the reduction depended on the replacement of OPC by FA rather than on the fineness of FA.2 content available from OPC.The use of RS to partially substitute OPC reduced ASR expansion of the mortar by decreasing the Ca(OH)The filler effect of RS is a factor that contributed to the reduced ASR expansion of the mortar. Moreover, the filler effect of RS with a higher fineness was more effective than that of RS with a lower fineness.The use of Class C FA with different levels of fineness (retained on No. 325 sieve at 5 and 33% by weight) to replace OPC at 20% reduced the ASR expansion by more than 50% at 14 days. In addition, it is suggested that reducing the CaO content (by reducing the OPC content) in mortar could be more effective in mitigating the ASR expansion than the filler effect of the cement replacement material.Based on the results from this study of the influence of cement replacement with fly ash and ground sand with different fineness on the alkali-silica reaction of mortar, the conclusions can be summarized as follows:


The design of novel multifunctional materials based on nanoparticles requires tuning of their magnetic properties, which are strongly dependent on the surface structure. The organic coating represents a unique tool to significantly modify the surface structure trough the bonds between the ligands of the organic molecule and the surface metal atoms. This work presents a critical overview of the effects of the organic coating on the magnetic properties of nanoparticles trough a selection of papers focused on different approaches to control the surface structure and the morphology of nanoparticles’ assemblies. Since the pioneering works of Louis Néel in 1944 ,6,7,8,9,Entering the nanometer-scale regime (<100 nm), the magnetic properties of materials change progressively with decreasing size until they show substantial differences with respect to the bulk state when the fraction of atoms lying on the surface becomes larger than that in the particle core, making the role of the surface dominant. For this reason, in the last decades ever-increasing interest has been devoted to approaches aimed at controlling the contribution of the surface to optimize the magnetic properties for meeting the requirements for specific applications. −increase of magnetic anisotropy due to the surface contribution arising from the random spin pinning on the surface. The “surface anisotropy” was described by Néel , using a−decrease of saturation magnetization in ultrasmall particles because of the surface spin disorder that makes the surface magnetically inactive (dead layer). This represents a strong limitation for those applications of nanoparticles requiring high particle moments.The surface structure is disordered, due to the breaking of lattice symmetry, with random missing bonds and then incomplete atomic coordination sphere with respect to the atoms in the core and in the bulk state. This induces significant changes in the magnetic properties of nanoparticles, which become more and more important with decreasing particle size, i.e., increasing surface/volume ratio:The surface ,26 contr−increase of the particle saturation magnetization, due to the contribution of the surface, becoming magnetically active ,31,32,33−decrease of the particle anisotropy, due to the decrease of the surface contribution ,34.The nanoparticles can be functionalized by a post synthesis process allowing to finely tune the magnetic properties of the single particle. The main effects of the reduction of the surface disorder produced by the organic coating on the magnetic properties are:−controlled change of the interparticle distance, functionalizing the particles with molecules of proper steric features, allowing in such a way a tuning of the strength of dipolar interparticle interactions, which contribute to the effective anisotropy ,38.−controlled change, by specific ligands, of morpho-structural features of the particle assembly, i.e., size, shape and the crystalline structure of NPs during the synthesis process, strongly affecting the resulting magnetic state and its thermal stability ,40,41.A fine tuning of both saturation magnetization and anisotropy can be achieved through the control of the role of the factors that were found to significantly affect the above properties, such as the type of functional group of the ligands, their chain length, the nature and the strength of the bond (monodentate or bidentate), the packing density of the coating molecules, the electronic structure and surface disorder of the original particles, which depend on the synthesis route. It is worth pointing out that, due to the complexity and the number of the involved factors, in some cases contradictory results  are observed, ,36 in oxBesides the effects on the magnetic properties, magnetic coating can provide new selective surface functionalities exploitable for several applications and can control the physical and chemical stability of nanoparticles avoiding aggregation and favoring their biocompatibility.In this framework, the present paper is aimed at providing a critical overview, through a selection of publications on the different effects produced by the organic coating on the magnetic and morpho-structural properties of nanoparticle assemblies.(a) Tuning of saturation magnetization and anisotropy(b) Control of interparticle interactions(c) Control of morpho-structural propertiesThe paper is structured in sections focused on the following effects:S) , in excellent agreement with the magnetization results [MS (PVA) /MS (oleic) = 0.71]. By means of high-resolution electron microscopy measurements, the authors correlated the different nanostructures, arising from different synthesis procedures, to the spin and orbital contribution to the magnetic moments.The effect of the type and strength of bond between the organic molecule and the particle surface was also investigated by N. Pérez et al.  on 5 nm urements  showed a2O4 nanoparticles is compared to that of diethylene glycol (DEG) by Vasilakaki et al.  and TMA (tris (2-pyridylmethyl) amine). A sample functionalized just with TMA was used as a reference. The presence of the {CoII(TPMA)}2+ complex at the surface of the nanoparticles and the formation of an oxo-bridge between Co(II) and Fe(III) ions were evidenced by XPS, AAS and XAS measurements. The temperature of the maximum in the ZFC curves was higher for [CoII(TPMA)Cl2] sample (Tmax = 30 K) than for the reference one (Tmax = 11 K). Hysteresis loops at 5 K showed a much larger coercivity for the [CoII(TPMA)Cl2] (Hc ~840 Oe) with respect to the sample prepared with addition of Tetramethylammonium hydroxide (Hc ~60 Oe). In agreement with the above measurements, 57Fe Mössbauer spectra at 77 K indicated a slowdown of the relaxation phenomena of the magnetization, due to the attached Co(II) complexes which increased the magnetic anisotropy of the Fe(III) moments, strengthening thus the magnetization of each nanoparticle. Fe and Co specific  XMCD-detected magnetization curves at 5 K are superimposed demonstrating that the Co(II) was magnetically coupled to the Fe(III) ions of the maghemite nanoparticles  and diethylene glycol (DEG). Lower anisotropy and larger MS (~120 emu/g) were found for the DEG coated sample with respect to the OA coated one (~82 emu/g). For an assembly of single-domain particles with uniaxial anisotropy and magnetization reversal by coherent rotation, the type and strength of interparticle interactions can be estimated using DM plot (ΔM(H) = MDCD(H) − (1–2 × MIRM(H)) through the Wohlfarth model [S, but also to a shorter interparticle distance between DEG coated particles. In the OA sample, for each particle a ~2 nm thickness of oleic acid produces a total distance of ~4 nm between surfaces. On the other hand, the side chain link of the shorter chain DEG produces a single layer of 0.5 nm with a total distance of 1 nm among particles’ surfaces. The above thicknesses of the OA and the DEG molecules were estimated by a simple calculation starting from density and surface area for 1 g monolayer. The calculated dipolar interactions energies are ~31 K and ~12 K for DEG and OA sample, respectively. The ratio between dipolar energies and DM plot intensities is exactly the same, due to the contribution of the coating to both the saturation magnetization and the interparticle distance. The stronger dipolar interactions in the DEG coated sample results also in a larger blocking temperature with respect to the OA coated sample.Vasilakaki et al. in their paper , discussth model ,51. As sS 70 emu/g; μ0Hc ~1.3 T) was submitted to thermal treatments at 350 °C  and 500 °C . The effect of molecular coating on the interparticle interactions and anisotropy of cobalt ferrite nanoparticles was also investigated by Peddis et al. . NanoparS. On the other hand, the treatment at 500 °C induces an increase of particle size and then the further increase of interparticle interactions can be ascribed to the increase of the particle moment . The largest field corresponding to the ΔM peak in the sample without surfactant is a clear indication that the elimination of the molecular coating induces a significant increase of magnetic anisotropy, as confirmed by the increase of coercive field and the effective anisotropy constant.For the three samples, the DM plot shows a negative peak, indicating the predominance of dipolar interparticle interactions. The increase of the DM intensity after thermal treatments at 350 °C can be ascribed mainly to the decomposition of molecular coating . In fact, CoFe1 and CoFe1T350 samples, show equal value of particle size, quite close value of M3O4, CoFe2O4 and ZnFe2O4 with average size of ∼4.5 nm, was investigated by Virumbrales-del Olmo et al. [2O4 sample, carboxylate groups bridging bidentate act as ligands and in the case of Fe3O4 the ligands are chelating. However, for ZnFe2O4 the bridging bidentate and chelating ligands coexist at the surface of the particles. The values of effective magnetic volumes 2/25kB, where H and Hk are the applied and anisotropy field, respectively), Veff, for Fe3O4 and ZnFe2O4 samples  are less than twice the experimental particle volumes, VTEM,  indicating that in these samples 1–2 particles are interacting. However, for the CoFe2O4 sample, Veff (331 nm3) is an order of magnitude higher than VTEM (45 nm3), i.e., aggregates of 7–10 nanoparticles. These results suggest that for Fe3O4 and ZnFe2O4 nanoparticles the protecting organic layer minimizes the interparticle interactions, while for CoFe2O4 NPs, despite presenting a similar particle–particle distance (∼2 nm), the molecular coating has less effect on the interparticle interaction. This can be ascribed to the interplay existing to interparticle interactions and magnetic anisotropy, a point that still needs some investigations [The effect of the oleate ligands on the interparticle interactions and surface anisotropy of three different capped nanoparticles, Feo et al. . The parigations ,49.The control of interparticle interactions, trough the surface coating, can be exploited in some applications improving the performance of nanoparticle based magnetic materials. An interesting example, related to biomedicine, is given by Blanco-Andujar et al. . They in2kg−1) and higher (4.1 nHm2kg−1) ILP values. Room temperature 57Fe Mössbauer measurements showed that the samples consist of a mixture of magnetite (25–35 wt%) and maghemite particles. In order to investigate the interparticle interactions, field dependent measurements of the remanent magnetizations  have been performed at 5 K  and 2 mmol (CA-ioH) CA in solution, showed the lower  strongly affecting the magnetic properties ,53,54,55TG and FT-IR analyses showed that oleic acid forms covalent bidentate bonds with metal ions on the particle surface and a complete monolayer at a critical concentration. Without oleic acid, agglomerated nanoplatelets with a crystallite size of about 19 nm were observed by XRD and TEM . A decreThe effects of coating magnetite nanoparticles (Fe0) by oleic acid (FeOA) and phosphate (FP1) on the morpho-structural features and magnetic properties were investigated and compared by Muthukumaran and Philip . It was On the other hand, the strong interaction of phosphate ions with the NPs appears to arrest the crystallite growth before attaining a sufficient growth to reach uniform size and shape, which is evident from the identical broad size distribution pattern of FP1 to that of Fe0.2Fe2O4 spinel nanoparticles (average size 7.4 nm) was investigated by Aslibeiki et al. [d), which was found to decrease by increasing the TEG content, reflecting the tendency to the saturation and the decrease of magnetic disorder at the surface  MnFei et al.  by magnei et al. .By means of first-principles calculations, based on spin-polarized density functional theory, of the electronic structure, relaxed structures were determined for both the uncoated and albumin coated particles. The clusters are surrounded by the long albumin molecules and then they do not touch each other, whereas the nanoparticles in the clusters are in physical contact . The coaM.C. simulations, which assumed spherical particles with core/shell randomly located at the nodes of a cubic lattice, accounting for both intra and interparticle contributions to the Hamiltonian, are in very good agreement with the results of experiments.The selected papers provide evidence of the key role of the organic coating on the tuning of magnetic properties of nanoparticles. The exploitation of the effects induced by the molecular coating offers a great opportunity to design novel nanostructured magnetic materials (composite and hybrid nanomagnets) opening enormous prospects in the realization of advanced polyfunctional magnetoelectric devices. Moreover, the molecular coating of magnetic nanoparticles, combining inorganic magnetic cores (mainly oxides) and organic shells, plays a very important role in biomedicine (for diagnosis and therapy of tumor cells) not only controlling the anisotropy and increasing the saturation magnetization, making NPs more efficient since they are magnetically driven, but also enhancing their bio-cytocompatibility.In order to optimize the magnetic properties of nanoparticles for specific applications a deep knowledge of the mechanisms through which the molecule ligands bind to the surface cations is required to understand the role of the many different factors involved . The investigations reported in the selected papers provide a contribution to the knowledge of such mechanisms and to a deeper understanding of the surface magnetism effects and their role in controlling the fundamental properties of magnetic nanoparticles. However, the effects of the complex interplay of such factors are not fully clear yet and further investigations are necessary requiring an interdisciplinary approach involving skills in different research fields, such as matter and surface physics, organic and inorganic chemistry and specifically coordination chemistry.


With the development of infrastructure, there are growing numbers of high geothermal environments, which, therefore, form a serious threat to tunnel structures. However, research on the changes in mechanical properties of shotcrete under high temperatures and humid environments are insufficient. In this paper, the combination of various temperatures (20 °C/40 °C/60 °C) and 55% relative humidity is used to simulate the effect of environment on the strength and stress–strain curve of basalt fiber reinforced shotcrete. Moreover, a constitutive model of shotcrete considering the effect of fiber content and temperature is established. The results show that the early mechanical properties of BFRS are improved with the increase in curing temperature, while the compressive strength at a later age decreases slightly. The 1-day and 7-day compressive strength of shotcrete at 40 °C and 60 °C increased by 10.5%, 41.1% and 24.1%, 66.8%, respectively. The addition of basalt fiber can reduce the loss of later strength, especially for flexural strength, with a increase rate of 11.9% to 39.5%. In addition, the brittleness of shotcrete increases during high temperature curing, so more transverse cracks are observed in the failure mode, and the peak stress and peak strain decrease. The addition of basalt fiber can improve the ductility and plasticity of shotcrete and increase the peak strain of shotcrete. The constitutive model is in good agreement with the experimental results. A growing number of railway and highway tunnels are being constructed imminently in the Sichuan–Tibet region of China with the advancement of the “The belt and The Road” strategy. The engineering of high geothermal phenomena occurs more frequently due to geological structure, magmatic activity, groundwater activity, and other factors. This special environment leads to adverse effects on building procedure, while the tunnel construction deteriorates in long-term service . TherefoGenerally, one of the main functions of high temperature is considered to be accelerated cement hydration, resulting in the rapid but highly non-uniform formation of a structure. This is beneficial to the development of early strength, although the increase in defects in concrete also causes a decrease in homogeneity, and the coarsening of the pore structure degrades mechanical properties ,3. The eHence, many scholars have concentrated on improving the high-temperature properties of shotcrete and found that the incorporation of fiber is one of the effective methods ,9,10,11.In sum, previous findings have confirmed the importance of temperature and humidity in tunneling. However, the application of lining concrete in the compound environment of high temperature and relatively low humidity is still insufficient; the low humidity environment will aggravate the shrinkage and cracking of concrete and damage the lining structure, which will have a great influence on the strength of concrete and the coordinated deformation ability of lining and surrounding rock, and the effect of common methods used to optimize properties of concrete is also unclear under this environment. Meanwhile, the only strength variation is dissatisfied with the deformation design of the lining structure, and it is necessary to further explore the relationship between concrete deformation and constitutive. Therefore, in this paper, a similar environment was established to simulate the high geothermal environment while basalt fiber was used to alleviate the degradation of the tunnel structure. Compressive strength, flexural strength, and the axial compressive stress–strain curve of basalt fiber reinforced shotcrete (BFRS) in a high geothermal environment were studied and a constitutive model was proposed.Ordinary Portland cement (OPC) was used as binder. Its chemical cpmposition and physico-chemical properties are shown Five types of shotcrete were prepared in this experiment, their mixture proportions are presented in According to the measured temperature and humidity of the Sichuan–Tibet Line Sang Chu Ling Tunnel , the temAn electro-hydraulic press with a capacity of 1000 kN was used for the compressive strength test. The stress–strain test was carried out on a universal material testing machine. Two displacement sensors were arranged on the adjacent surfaces of concrete. A constant displacement rate of 0.1 mm/min was set to control the loading. The test site is shown in fc is the flexural strength of shotcrete, MPa; P0.1 is the peak load of the specimen, KN; L is the span between supports of beam specimens; b is beam width; d is beam height.Flexural strength was accessed by four-point bending test and the result was calculated according to Formula (1).The influence of curing temperature on the compressive strength of shotcrete is shown in High temperature could accelerate the cement hydration and the formation of the gel network, leading to an increase in early age mechanical properties of the shotcrete. However, excessive curing temperature is often accompanied by over-quick hydration. This implies that the stable structure of the matrix is formed before the hydration products spread evenly, and therefore many defects in micro scale exist in the matrix. Meanwhile, due to quick evaporation of water, a larger shrinkage stress arises. Under the combined action of the two, the strength of shotcrete may deteriorate. When 0.3% BF is incorporated, the effect of temperature on the flexural strength of shotcrete produces a slight deviation, which will be discussed below.Adding 0.3% of BF will decrease the quality and increase the inner shortcomings of shotcrete, and negatively affects the process of the compressive strength. Incorporating fiber into shotcrete is useful to keep the shotcrete from splitting and decreases the degradation of flexural strength that results from the high temperature environment ,20.Then, the curing temperature of 60 °C, at which shotcrete performance deteriorates the most, is selected to study the effect of fiber content and the results are shown in The destruction form of shotcrete under axial compression is presented in The stress-strain curve of shotcrete at different curing temperatures is shown in The peak stress and peak strain of shotcrete at different curing temperatures are shown in The stress-strain curves of BFRS with different content cured at 60 °C are shown in At the age of 7 days, the incorporation of moderate fiber can make the stress–strain curve of BFRS wider and flatter while the slope of the upward section becomes smaller. This is the reason why the peak value shifts to the right and decreases slightly. At the age of 28 days, the effect of fiber shows a similar phenomenon to day 7. After curing for 60 days, the peak point of the BFRS curve with the 0.3 and 0.4% content moves to the right, and the curve is smooth and full. However, the length of the BFRS curve with 0.1 and 0.2% content is obviously shorter, showing greater brittleness.The peak stress and peak strain of shotcrete with fiber are shown in At the age of 7 days, the peak strain of BFRS is higher than that of reference, and 0.3% attains the maximum of 91.6%. At the age of 28 days, the peak strain of the 0.1% and 0.2% increased by 26.2% and 42.8%, respectively. After being cured for 60 days, less BF will lead to a decrease in peak strain of BFRS, while the peak strain of the 0.3% and 0.4% increased by 68.8% and 58.3%, respectively. It can be seen that high temperature can significantly improve the peak strain of concrete. When damaged hardened paste loses its bearing capacity, fiber can partly bear capacity and restrict the deformation of surrounding rock ,25, resux = ε/εp,t, y = σ/σp,t,After comparative analysis, this paper selects the concrete compressive stress-strain constitutive relation proposed by Professor Guo as polynomial and rational, as shown in the following formula ,28.(2){s larger ,30.According to Equation (1), the stress-strain curve of concrete is normalized ,32, and The stress-strain fitting curve of shotcrete at different temperatures is shown in The stress-strain fitting curve of fiber shotcrete with different contents is shown in With the increase in age, the fiber has little effect on b value. This is the reason why the lower circumference area of BFRS in the curve becomes larger, indicating the energy dissipation effect of BF in shotcrete will improve the toughness and result in better plastic ability .By fitting the ascending and descending sections of the stress-strain curve of shotcrete without fiber at 60 days, the relationship between the curing temperature of shotcrete and the parameters a and b of the ascending section and descending section can be obtained, as shown in Equation (3).In order to obtain the influence of basalt fiber content on the parameters a and b in ascending and descending sections, the influence coefficient λ of basalt fiber content is introduced into Equation (3), and Equation (4) is obtained. The influence coefficient λ of basalt fiber content is obtained from the parameters of the ascending section and descending section of BF-0.1, BF-0.2, BF-0.3, and BF-0.4 in x = ε/pεt,, y = σ/pσt,, and ε and σ are the stress and strain of basalt fiber shotcrete, respectively.The stress-strain constitutive equation of BFRC in a high geothermal environment can be obtained by combining Equation (4) into (2), as shown in Equation (5).(1)High temperature curing can improve the early compressive strength of shotcrete, but it is not good for the development of its early flexural strength. After curing for 28 days, both the compressive strength and flexural strength decrease to varying degrees. The addition of fiber can reduce the strength deterioration of shotcrete caused by high temperature environment conservation, and the effect increases first and then decreases with the addition of fiber. The optimum basalt fiber content is 0.3%.(2)High temperature is attributed to the decrease in the peak stress and strain of shotcrete, and showing a greater brittleness, and the stress-strain curve becomes sharp and steep. Meanwhile, the fiber increases the peak strain of concrete, up to 91.6%, resulting in an increase in the plasticity and ductility.(3)According to the relationship between peak stress, peak strain, and axial compression, the stress-strain curve parameters a, b and temperature and basalt fiber content of concrete were analyzed, and the constitutive equation of shotcrete in a high geothermal environment is established.In this paper, the effects of high temperature and fiber content on the strength and uniaxial compression constitutive relation of basalt fiber reinforced shotcrete under high ground temperature are studied. The main conclusions are as follows:At present, the researchers of shotcrete in high geothermal environments are more focused on the material and structure level, and the hydration process and mechanism of shotcrete in high geothermal environments need to be further studied. In addition, it is necessary to carry out in-depth research on the damage mechanism and influence law of mechanical properties and durability of shotcrete under the actions of temperature, surrounding rock pressure, and erosion ion coupling, not only staying at the level of temperature influence, but also to provide support for tunnel durability design.