Currently, there are no available tools in Poland for assessing the knowledge and attitudes of specialists in health sciences towards EBP. Therefore, by validating the Polish version of the original English Evidence-Based Practice Profile Questionnaire , validity , as well as unidimensionality of domains .The validation group consisted of 1,362 people, including nurses and midwives taking the specialization exam, second-degree students in nursing/midwifery, and staff of selected municipal and clinical hospitals in Warsaw, Pruszkow, and Chelm. The study was conducted from March to June 2014. The following psychometric properties of the EBP2Q were characterized by high reliability . The Polish version showed a strong similarity of factor structure with the original English EBP2Q, indicating that the condition for theoretical validity is fulfilled. Maintenance of the theoretical and discriminative validity and unidimensionality of five domains of the EBP2Q was confirmed.All domains of the EBP2Q is comparable in terms of psychometry to the original English version. This questionnaire can be used to assess knowledge, attitudes, and skills concerning EBP among students and practicing professional nurses and midwives. The future validation of the EBP2Q in other groups of specialists in health sciences may increase the scope of applicability of this tool.The Polish version of the EBPThe online version of this article (doi:10.1186/s12909-017-0877-4) contains supplementary material, which is available to authorized users. The paradigm of Evidence-Based Practice (EBP) is based on an assumption that clinical decisions in patient care are an outcome of patients’ values, clinical circumstances and the best research evidence . It is aAs a result of the above benefits arising from application of EBP principles, there is an increased focus on formation of EBP-related attitudes and skills in under- and post-graduate education , 6. In oImplementation of appropriate educational solutions that are tailored to the individual needs of a particular group requires a preliminary assessment of competencies with the use of standardized questionnaires . Most toEvidence-Based Practice Profile Questionnaire (EBP2Q) [Evidence-Based Practice Questionnaire for Nurses [Evidence-Based Nursing Attitude Questionnaire [Evidence-Based Practice Attitude Scale [Developing Evidence-Based Practice Questionnaire [Evidence Based Practice Evaluation Competence Questionnaire [2Q [2Q was developed at the University of South Australia by a team led by Maureen McEvoy, and was validated on 526 people  [2Q is its application to self-assessment of EBP competences by students, lecturers, and practitioners [2Q.Globally, a few types of questionnaires for assessing EBP are available, including: the  (EBP2Q) , the Evir Nurses , 18, theionnaire , the Evide Scale , the Devionnaire , and theionnaire . Althougionnaire , furtheraire [2Q . The EBPtioners) . Apart fitioners . It can itioners . The pur2Q consists of 58 statements , allowing the assessment of five domains  by the respondent. It is supplemented with additional questions necessary for the sociodemographic characteristics of respondents. In addition, the EBP2Q contains 16 statements, which have not been assigned to any of the five domains in the course of validation ; (2) second-degree students of nursing and midwifery at the Medical University of Warsaw and the Higher Vocational School in Kalisz (N = 462); and (3) nurses working in municipal and clinical hospitals in Warsaw, Pruszkow, and Chelm (N = 304). The study was conducted from March to June 2014. Participation in the study was voluntary and anonymous. Results were collected using an auditorium questionnaire, in which respondents were gathered in a single room at the hospital to complete self-administered questionnaires and the completed questionnaires were subsequently pooled.The study involved 1,362 people, including 1,195 (87.7%) women, 42 (3.1%) men, and 125 persons (9.2%) who did not respond to the question regarding sex. The average age was 39.4 years . The study group consisted of three subgroups: (1) nurses and midwives taking the state specialization exams organized by the Centre of Postgraduate Education for Nurses and Midwives in the spring session in 2014  that determine the level of consistency of answers given between the first and the second measurement [t test [2Q [The test-retest reliability was assessed in a group of 160 students who were retested using the EBPsurement . To esta [t test . The cri2Q was assessed using three different analytical approaches. First, estimation of theoretical validity, also known as the internal validity, was performed by exploratory factor analysis. In particular, we explored whether the factor structure of the EBP2Q consists of five domains. Two different factor analysis criteria were used: (1) the Kaiser criterion, based on the number of factors with eigenvalues over one [2Q), while the more conservative approach based on the scree plot gives more reliable results [N = 119) while the control group did not participate in additional EBP classes (N = 207). A detailed training course had been previously published by Panczyk et al. [t test was used to compare the groups and Cohen’s d was determined as a measurement of the effect of differences between means. The following criteria were assumed to assess the measured effect size: very strong ≥0.80, strong 0.50–0.79, average 0.49–0.20, and poor <0.2 [The validity of EBPover one ; and (2)over one . Both cr results . The fulk et al. . The t toor <0.2 .2Q domain was performed using principal component analysis. A domain was considered unidimensional if it met the Kaiser criterion [The analysis of unidimensionality of each EBPriterion   caused a slight increase in the value of the coefficient by 0.016 . In addition, the value of the determinant of the correlation matrix was close to zero (1.4∙10−28). Furthermore, the condition for sphericity was fulfilled, as it was found that a correlation coefficients matrix is not an identity matrix . The last condition of factor analysis was evaluated by the KMO test to assess the expected reduction rate. Adequacy of sampling (KMO index) was 0.949, which fulfills the assumptions for this parameter (KMO > 0.5).Before we estimated theoretical validity using factor analysis, we verified the fulfillment of the assumptions for this method. No statements showed a standard deviation of zero, and we confirmed the presence of homoscedasticity  indicated five domains Fig. . In the 2Q. All domains proved to be theoretically valid. Only item No. 15 from domain II (Sympathy), did not load as expected with other statements of this domain. The result of the rotation indicates that this item belongs to domain I (Relevance) rather than domain II (Sympathy). Detailed summary of the results of the factor analysis for the direct oblimin rotation of loadings are included in Additional file To facilitate the interpretation of the obtained non-orthogonal solution, direct oblimin rotation of raw factor loadings was performed. The resulting solution largely confirmed the proposed structure of the EBP2Q was also evaluated by calculating the Spearman’s rank correlation coefficients based on the sum of the scores calculated for each of the domains. For domain II (Sympathy), a weak correlation with domain I  was found. No significant positive correlation with other domains of the EBP2Q was found (Table rs = 0.60) and “Practice” and “Terminology” (rs = 0.51).Theoretical validity of the EBPnd Table . Particud 0.29–0.43). In the case of domain V (Confidence), however, the difference was on the border of statistical significance and the effect size was small . No significant effect was noted for the students’ score in domain IV . The results of the validity assessment using the inter-group differences method are presented in Table Within three domains  the mean score of the students participating in the EBP training was significantly higher compared with that of the control group students. EBP training had a small to medium effect size on scores within these three domains  to assess EBP in Poland [Although the concept of EBP has been known for decades, this concept is not widely known in the Polish nursing and obstetric environment . With thn Poland . This is2Q is intended for use in a diverse group of nurses and midwives, as well as among students in these fields, a heterogeneous validation sample was chosen. We assume this provides adequate representation for evaluation of the psychometric parameters of the EBP2Q and its standardization across the various groups [2Q. The reliability of the individual domains clearly exceeded the recommended value  [2Q, in which Cronbach’s alpha ranged from 0.760 to 0.940 [2Q contributes to a high degree of confidence in the measurement results obtained. This is linked to the low level of random errors, which do not exceed 10–20%. Thus, random fluctuations in test results described in the classical theory of psychometric tests do not reduce the value of alpha in this case [As the Polish EBPs groups . Our psyo 0.972) , 26. Ourto 0.940 . The highis case .2Q. Both the values of the ICCs (the Polish version: 0.68–0.97 versus the English version: 0.77–0.94) and the differences between the means (the Polish version: 0.42–1.50 versus the English version:−1.07–0.52) for the repeated measurements in individual domains of the EBP2Q were comparable to the results of the test-retest analysis published by McEvoy et al. [2Q appears to have good parameters of absolute stability. This means that the results of the measurements in the individual domains of the EBP2Q show limited sensitivity to random changes [The results of the test-retest reliability analysis were also similar to those obtained during the validation of the original version of the EBPy et al. . The resy et al. , it is h changes .2Q obtained during the psychometric evaluation indicate a fairly high degree of similarity in the scope of tested knowledge and attitudes among study participants. We found a small degree of variation in the validation group, which indicates high uniformity in measured traits (SD ranged from 0.81 to 1.38). These results are similar to those obtained by McEvoy et al. [2Q   and the degree of expected reduction KMO index for the English version 0.92 versus 0.95 for the Polish version) were similar in both studies [2Q was found to be largely consistent with the validated English version. We only observed variability in domains I and II (Relevance and Sympathy). This is probably related to a different organization of the work environment and a slightly different scope of competencies of nurses in Poland and Australia. Generally, despite some differences, the results of analysis of the theoretical validity confirm a high degree of accordance between the planned Polish and validated English EBP2Q in evaluating the knowledge and attitudes toward EBP.The assumptions for the validity assessment by factor analysis were the same as those applied in the validation of the English version of the questionnaire . Both th studies . The dom2Q also confirms the high quality of the measurement tool. Results of respondents, calculated as the sum of the scores obtained for the individual domains, were positively correlated with each other. The exception was domain II (Sympathy), which is associated with the design of the items constituting this domain. In particular, some of the items within domain II directly overlap with those found in domain I (Relevance) and were similar to those found in all other domains. It can therefore be assumed that the individual intercorrelations for the EBP2Q components confirm the fulfillment of the condition of theoretical validity. Therefore, some theoretical assumptions related to the construction of the EBP2Q were confirmed by empirical observation, and the functioning of the Polish version is similar to the English EBP2Q.The theoretical validity of the Polish EBP2Q, McEvoy et al. [2Q, two groups were compared . For both tests, significant differences between the groups concerned the results of the measurements in domains I and III (Relevance and Terminology). As expected, both tests also showed no significant training effect on the results achieved in domain IV (Practice). The differences in the assessment of discriminative validity relating to domain V (Confidence) may be connected with different durations of EBP training in the validation tests. The method of conducting the EBP training is crucial to its effectiveness. Therefore, variations in training programs, including their duration (the Polish version: 12 h versus the English version: ≥20 h) and form (the Polish version: e-learning versus the English version: EBP course as part of university education), may have significantly contributed to the observed differences.Regarding the assessment of discriminative validity, the validation tests slightly differed across studies in how they were performed. For the original version of the EBPy et al.  proposed2Q was evaluation of unidimensionality of individual domains. As in the case of validity analysis, these results confirm the factor homogeneity of all the domains, with the exception of domains I and II. In particular, domain II was highly heterogeneous, which directly refers to the results of the evaluation of criterion validity parameter. As mentioned above, this may result from potential differences between Poland and Australia in terms of working conditions and professional competence of nurses or midwives.The last element of psychometric assessment of the Polish EBP2Q allow us to assume that it can be used in practice as a tool for assessing the EBP-related competence of students and practitioners in the nursing or midwifery profession. The EBP2Q is a tool for measuring the knowledge, attitudes, and behavior of subjects in the field of EBP. The results of this assessment can be used to diagnose the barriers that hinder the implementation of EBP in the workplace. Moreover, the EBP2Q can be successfully used by the participants of courses to upgrade their skills in the field of EBP, both as an element of self-assessment, as well as a tool for measuring learning outcomes. The questionnaire can be also used when designing individual educational programs, indicating those areas of knowledge and skills to which particular attention should be paid in the learning process. Furthermore, the modular nature of the EBP2Q is its undoubted advantage. In particular, the tool can be adjusted to the needs of an individual test by using only selected domains.The unambiguous results of the psychometric analysis of the Polish version of the EBP2Q, as any tool, has some drawbacks. One of them is the impossibility to assess a subject’s use of other types of evidence than scientific. Making clinical decisions on the basis of non-scientific evidence, personal experience, tradition or intuition is contrary to the EBP concept. The knowledge of subjects’ attitudes to the use of non-scientific evidence in medical practice could boost the measurement validity. Another important drawback of the EBP2Q pertains to domain III (Terminology). This domain relates to the knowledge of certain terms connected with methodology of scientific research, but it includes only the knowledge around quantitative based terms and excludes terms connected with qualitative research.The EBP2Q. In addition, further validation studies should assess the diagnostic ability of the Polish EBP2Q, by performing research using the tool in educational situations .One of the significant limitations of the present study is the lack of convergent validity analysis, it was not possible to determine this psychometric property due to the lack of another Polish tool available for evaluating similar domains to the EBP2Q confirm the high quality of this tool. In terms of reliability and validity, the Polish EBP2Q is comparable to the original English version. The questionnaire can be used both in educational activities (graduate and postgraduate studies), as well as an assessment tool among practicing professional nurses and midwives at various levels.The results of the psychometric analysis of the Polish EBP


The object of this work was the deposition of a Ta-Hf-C thin film with a gold interlayer on stainless steel, via the physical vapor deposition (PVD) technique, in order to evaluate the properties of different systems subjected to micro-abrasive wear phenomena generated by alumina particles in Ringer's solution. The surface characterization was performed using a scanning electron microscope (SEM) and atomic force microscope (AFM). The crystallographic phases exhibited for each coating were obtained by X-ray diffraction (XRD). As a consequence of modifying the composition of Ta-Hf there was evidence of an improvement in the micro-abrasive wear resistance and, for each system, the wear constants that confirm the enhancement of the surface were calculated. Likewise, these surfaces can be bioactive, generating an alternative to improve the biological fixation of the implants, therefore, the coatings of TaC-HfC/Au contribute in the development of the new generation of orthopedic implants. In the field of orthopedic implants , biomateAs a result of the requirement for improving the wear resistance, the PVD technique has allowed the deposition of thin films that modify the physical and chemical properties of the surface without modifying the mechanical properties of the substrate ,11,12. TAnother material that is implemented in the biomaterials field is hafnium, as the addition of this material stimulates an improvement in wear resistance and surface integrity against deformation ,18. FurtThe use of solid lubricants as a thin film has increased since traditional lubricants cannot reach some restrictions in the environments that require specific conditions, such as extreme temperatures , vacuum In the other hand, in thin films there exists a correlation between surface hardness and the coefficient of friction. At a higher hardness the coefficient of wear is lower, improving the response to wear phenomena ,27. To iThe aim of this work was to perform a deposition on 316LVM stainless steel with a coating of HfC/Au, TaC/Au, and mixtures of TaC-HfC in which the behavior of micro-abrasion wear in simulated biological conditions was evaluated. It was determined that the coatings improve against wear.−7 Pa was used.For the deposition of different coatings targets 50.8 mm diameter comprised of gold, tantalum, and hafnium with 99.95% purity and a carbon target with 99.999% purity were used in a confocal configuration at 0.4 Pa pressure in argon. For the deposition of different films the non-reactive magnetron sputtering technique in an AJA-ATC 1800 UHV equipment with a base pressure of 10Previously, the deposition of the films on substrates of 316LVM stainless steel were cleaned with ethanol and, subsequently, with plasma at a radio frequency (RF) with a power of 25 W in a pure argon environment at a pressure of 4 Pa for 10 minutes. Prior the deposition of the gold film, and to enhance the adhesion of the film to the substrate, was deposited a thin metallic layer of Ta-Hf with a thickness of approximately 20 nm between the substrate and the gold film by applying an RF power of 100 W to each Ta-Hf target. The gold films were obtained by applying a direct current (DC) power of 150 W to the gold target with a substrate rotation of 80 rpm for 20 minutes at room temperature, obtaining a thickness of 0.8 µm.For the deposition of the different Ta-Hf-C films , the power applied to the targets was varied in the following way: 100-0 W (TaC), 70-30 W (70TaC 30HfC), 30-70 W (30TaC 70HfC), and 0-100 W (HfC), while the power of the carbon target remained at 380 W. Deposition of the different films was carried out with a target-substrate distance of 15 cm and at a temperature of 300 °C, with a negative RF voltage of 50 V.The characterization of the crystalline phases was carried out on an X-ray diffractometer in a Bragg-Brentano configuration with a classic scintillation detector. The X-ray tube was made of copper with a Kα1 line of 1.540598 Å and Kα2 line of 1.544426 Å, with an incident ray radius of 240 mm. The voltage difference applied was 40 kV with an intensity of 30 mA, and the sweep interval was from 20 to 90°. The counting time designated for this test was stipulated at 2 s with a step size of 0.0400, for a total of 2125 points. Phase identification was performed in HighScore Plus software  with the ICSSD  and COD The micro-abrasion test was carried out in equipment that allows the simulation of the wear between two contact surfaces. The apparatus has a lever arm in which the sample is held and a fixed sphere between two coaxial axes. Through the movement of the counterweight, it is possible to regulate the load applied to the surface and the sphere, which is rotated by a DC motor with an encoder that guarantees control over the speed and number of cycles performed. Furthermore, a peristaltic pump adds a third body in the form of abrasive particles suspended in a solution to generate the micro-abrasive processes, as shown in With the aim to simulate biological conditions of a joint replacement by means of an ultra-high molecular weight polyethylene sphere and Ringer’s solution with alumina particles in suspension, the test parameters are shown in b is the average diameter of the scar and R is the radius of the sphere with which the test is performed. Relating Equation (1) with Archard's law of wear, Equation (2) is obtained, where K is the wear constant, S is the sliding distance, and N is the normal load applied:For the estimation of the wear rate parameter, a model that relates the dimensions of the wear path performed on the surface of the sample with a wear constant was considered. According to the authors Gee et al. ,33, the The surface was observed by a JEOL NeoScope JMC-5000 scanning electron microscope operating under high vacuum at 10 kV. Superficial roughness was evaluated by measuring the arithmetic average of the roughness profile (Ra) through a NaioSurf atomic force microscope reference, and the measurement was carried out with an image size of 46.2 μm × 46.2 μm with a 1 s time/line, a resolution of 256 points/line, and a setpoint of 20 nN using the contact mode with a silicon tip coated with aluminum. The measurements were performed in two different zones: The first zone of analysis was obtained prior to each wear test to characterize the surface. In the second zone, the analysis was carried out in the central area generated by the sphere to identify the wear suffered by the coatings. All of the measurements were repeated three times. Using SPIP Image Metrology software, the images were analyzed to obtain the average roughness for each system before and after the micro-abrasion test .2Au1 phase with planes in (103), (110), and (213), with a tetragonal crystalline system. On the other hand, the samples with a high content of tantalum, such as TaC/Au and 70Tac-30HfC/Au, show a match at 35.01° and 40.75°, which are attributed to the phase of Ta4C3.04, with (111) and (020) planes in a cubic crystalline system.In the interpretation of the crystalline phases of the coatings, the substrate was measured without any coating to identify the characteristics’ peaks that it presented, and subsequently identified the characterization of the different samples. In the samples with gold coatings, Through the scanning electron microscope technique the length of the scar generated by the wear process was measured. The measurement was carried out parallel and perpendicular to the direction of rotation of the sphere, as shown in Taking into account the average lengths, all of the tests were carried out with a normal force of 3 N and a sliding distance of 78.53 m, as used in Equations (1) and (2), to obtain the wear volume and the wear constants as shown in −4, which indicated great performance since the wear was moderate [The coating of 70Tac 30HfC/Au shows the lowest constant wear value, followed by the gold sample, indicating a superior behavior against the micro-abrasion wear compared with the other systems. On the other hand, the coatings’ performances of TaC, HfC, and 30TaC 70HfC were similar, where the highest value was exhibited by the HfC sample. Nevertheless, all of the coatings showed values in their constants lower than 10moderate .After the test was carried out measurements on the wear scar through SEM and AFM techniques were conducted to morphologically characterize the surface.In In In the micrographs obtained by AFM, On the other hand, samples of TaC/Au and gold showed a superficial variation considered average as a consequence of a morphological change that eliminated material and homogenized the surfaces. Finally, samples with a combination of TaC-HfC exhibited a slight morphologic change related with the other systems in addition to showing a lower roughness value.In the characterization of the crystalline phases it can be concluded that the gold coating had a major crystalline orientation compared with the other coatings since the gold thin film obtained by PVD showed a crystalline cubic structure, reflected in the counts obtained for this sample.2Au1 tends to replicate in both the pure HfC/Au samples, as well the 30TaC-70HfC/Au samples, and also the Ta4C3.04 phase was identified for the coatings of TaC/Au and 70TaC-30HfC/Au.Regardless of the varying deposition parameters, the crystalline phase of HfAll of the systems evaluated in this study had a good behavior against the phenomenon of micro-abrasion wear in the presence of Ringer’s solution, which is evidenced by the low values of the wear constants. Furthermore, although the HfC coating presented the highest value in terms of the wear constant, it shows advantages when it is in service since its roughness decreases significantly, generating a lower friction.Although the Au film showed signs of grooved debris by micro-abrasive processes, it was also one of the systems with the best behavior, due to exhibiting the second-lowest wear constant value. On the other hand, after the system of HfC/Au, the gold system showed a greater decrease in its roughness and had the lowest value related to the others coatings.Moreover, the coatings obtained via PVD allows generating a thin film that functions as a protective barrier against wear phenomena which is one of the main causes of failure of an implant due to deterioration and development of surface wear and cracks propagation. This degradation can extend through all the surface of the material and is important to avoid this kind of circumstance because in extreme cases can affect the structural integrity of the implant leading to the need of remove the implant.


High temperature superconducting (SC) nanocomposites based on SC ceramics and various polymeric binders were prepared. Regardless of the size of the ceramics’ grains, the increase of their amount leads to an increase of resistance to rupture and modulus and a decrease in limiting deformation, whereas an increase in the average ceramic grain size worsens resistance properties. The SC, thermo-chemical, mechanical and dynamic-mechanical properties of the samples were investigated. Superconducting properties of the polymer ceramic nanocomposites are explained by intercalation of macromolecule fragments into the interstitial layer of the ceramics’ grains. This phenomenon leads to a change in the morphological structure of the superconducting nanocomposites. Beginning with the discovery of high-temperature superconductivity in perovskite systems containing oxygen by Bednorz and Muller ,2, the lIn the literature, polymer ceramic compositions using thermoplastic and reactoplastic polymeric matrixes are already described in ,24,25,26etc.). This is mainly related to the formation of a special interfacial layer between the filler and polymeric binder. High-temperature SC polymer–ceramic composites can be obtained both by the conventional hot pressing of a mixture of ceramic and some ready-made high-molecular weight binder, and by the polymerization filler method  obtained for the samples after the restoration, is given in It had to be stated that the polymer-ceramic compositions with various binders used exhibit no superconducting properties right after hot pressing at 200 °C during 30 min., e.g., the Meisner effect is missing. Absence of SC properties can be explained by the depletion of oxygen from the orthorhombic super-conducting phase of the ceramic Yions see  under anSound proof of the assumption made above is the results of the experiments carried out when Irganox® 1010—a polymeric antioxidant—was added to the initial mixture of composition. As it is known ,30,31, acT) stays practically unchanged, whereas the transition end (fT) changes. In the samples without antioxidants, a wider (c–TfT) transition temperature span seems linked to a non-homogeneous distribution of the oxygen dislocated on the surface of the ceramic’s grain after the stage of restoration.Consequently, one can deduce that in this particular case, introduction of minute quantities (0.5 weight% of binder) of antioxidant in the polymer-ceramic compositions decreases the rate of the oxidation reactions and, consequently retards the depletion of the oxygen dislocated on the surface of the ceramic’s grain. Actually, in the compositions having small amounts of antioxidant, right after pressing and without the restoration stage, the samples possess super-conducting properties as follows from the data given in cT temperature elevation can be ascribed to the physical interaction of separate fragments of the macromolecules of the binder with the surface of the Y1Ba2Cu3O7-x ceramic, up to intercalation of these fragments into the interstitial layer of the ceramic’s grain or their anchoring in free oxygen positions. For the compositions with polyvinyl alcohol the observed decrease of cT by five degrees speaks to the possible interaction of some fragments of the polymeric chain with the surface of the ceramic. In this case OH groups, like in water, alcohol or weak acids . For the elucidation of such kind of anomalies, the influence of various quantities of the Y1Ba2Cu3O7-x ceramic on the kinetics of the polymerization of MMA in the presence and absence of AIBN was specifically investigated. A series of kinetic curves showing the influence of Y1Ba2Cu3O7-x ceramic on the polymerization of MMA in the presence and absence of ceramic is presented in Unexpected results were obtained while studying the influence of the Y1Ba2Cu3O7-x  begins from the surface of the ceramic when the content of filler in the reaction mixture is too high (90% by weight); the polymerization process is characterized by a high rate, and, presumably, is localized at the ceramic-monomer interstitial boundary.It is known that fixation of the ends of the macromolecules on the surface of the filler sharply decreases their mobility, and correspondingly—changes the kinetic parameters of polymerization, particularly, it substantially decreases the rate constant of the bimolecular rupture of the chains. This is the main reason of high steadiness of the process.In the reaction mixture, a second region appears in the kinetic curves of the polymerization with the increase of the concentration of the monomer, which speaks of the decrease of the rate of the process. Possibly this is conditioned by the accumulation of the polymer on the surface of the ceramic which hinders the accessibility of the molecules of the monomer to the active polymerization centers, e.g., occlusion of the active centers by the macromolecules occurs and the growth rate is controlled by diffusion.Besides, because of transference of the chain to the monomer——the kinetics of the process become salient at some MMA concentration value (20–25% by weight) with possible transition of the radicals from the surface of the filler into the bulk. Presumably, in this case the rate of blocked polymerization is lower than in the initial stages of implanted polymerization. This is because the diffusion retardation—imposed by the filler surface—is less conspicuous. Although, the presented qualitative model of the mechanism and topochemistry of the MMA on the surface of super-conducting ceramic satisfactorily describes the observed peculiarities, nonetheless this topic remains open for further study and discussion.σ), elasticity modulus (E) and elongation (ε) were determined at ambient temperatures, whereas for the binder made of SHMPE—at temperatures close 193 K, as well as at the superconducting state temperature of the composite (77 K). The magnitudes of σ, E and ε were determined via distention of the samples at ambient and 77 K temperatures, while at 193 K—under compression conditions. In the latter case the ceramic/binder ratio in the composites was varied as well.Determination of the physical–mechanical properties of superconducting polymer–ceramic nanocomposites is interesting, not only at ambient but in lower temperatures ranges as well, especially down to the critical transition temperature into the superconducting state. For the superconducting polymer–ceramic nanocomposites, the limiting strength of rupture  and end (fT) of transition into superconductive state for nanocomposites with cross-linked divinyl rubber.1Ba2Cu3O6.97 ceramic.As it follows from the data of E with an increase of the rate of filling evinces the presence of full contact in the polymer-filler interface, and the absence of scaling of the binder from the filler during the deformation of the tested samples. On the absence of scaling also indicate the curves stress vs. deformation  and on its end (fT).It is interesting that with the increase of average size of the ceramic particles, a tendency of increased deformation capacity of composite is observed. Here, most probably, the increase of particle size has a positive effect on the effectiveness of stopping the process of propagation of cracks at high degrees of deforming capacity. In 1Ba2Cu3O6.97 ceramic possesses the following superconducting characteristics: Tc = 93 K, Tf = 87 K. Juxtaposition of the initial ceramic of the composite with DR plus different particle size of the ceramic results in dissimilar superconducting properties. For the nanocomposites with mean particle size 5–10 μm, the value of Tc is lower by 5–10 degrees than for the initial ceramic.The initial non-fractioned YTc−Tf) widens as well. When the mean particle size becomes more that 20–25 μm, the critical parameters are sustained and even improved vs. the initial ceramic. Decreasing the critical temperature and increasing the transition width for the nanocomposites having mean particle size 5–10 μm, are related with two factors:Lesser content of the orthorhombic phase in the initial smaller particle size fractions of the ceramic;vs. the bigger fractions.Enhanced utilization of the oxygen in the reactions of thermo oxidation destruction of the binder Besides, the transition width  could be caused by two reasons. One is that the increase of quantity of SC ceramics leads to an increase of crystallinity. The second and more possible cause is that RPE macromolecules’ fragments intercalation 35], incrThe increase of the mechanical loss cannot be explained by the agglomeration of the small particles of the filler, because formation of such kind of aggregates can only take place at higher degrees of filling. It seems that the observed increase of mechanical losses is a result of an adsorption of the binder on the surface of the filler and intercalation of fragments of the macromolecules into the interlayer space of the ceramic grains. Such an interaction can change the structure of the polymeric matrix near the boundary of the particles, and—as a consequence—yield an increase of the mechanical losses.gT towards higher temperatures. It is assumed that the magnitude of the shift is proportional to the surface area of the filler, which explains the polymer-filler interaction.It is known that for some cases the filler shifts the maximum of mechanical losses and gT shift  increases, as shown in However, based on the obtained results, the dominant role of any of the mentioned factors cannot be definitely proved. For this purpose, it is necessary to conduct thorough electron-microscopic investigations of the nanocomposites samples.The investigation of the structures of SC polymer-ceramic nanocomposites by scanning electron microscopy has shown that for both the amorphous and the crystalline polymer matrices, a complete and uniform covering of the ceramic grains by the binder take place a,b,c.This indicates a strong interaction at the polymer-ceramic interface. The electron microscopic investigations of polymer–ceramic nanocomposite samples obtained under conditions of variable filling a,b,c pro1Ba2Cu3O6.97:i- PP = 85:15 ratio singular fibrils appear in field of vision of the microscope. With an increase of ceramic additive  and Cu2+(II). The first one is in the CuO chain along the axis direction, while the second is in the CuO2 planes along the ab plane. For a long time the nature of the Y1Ba2Cu3O7-x ceramic’s EPR response was unclear [It is known that high-temperature superconducting oxide ceramics possess their own localized magnetic moments producing a Cu unclear .2+ EPR signal intensity with simultaneous registration of X-ray Absorption Near Edges Structure (XANES) at the Cu2+k edges of the same signals [2+ EPR signal intensity dependence on the substitution degree of Cu2+(I) in Y1Ba2Cu3O7-x by Fe atoms showed [2+(I) in the chains and not to the Cu2+(II) in the CuO2 planes.Investigation ,37 of th2+(I) EPR signals depend on the binder. In 2+(I) EPR spectra are presented both for the Y1Ba2Cu3O6.97 and polymer-ceramic nanocomposites with various polymeric binders: polystyrene, polymethylmetacrylate and polyethylene, respectively. These facts demonstrate that the particles of the layered ceramic have nanocomposite structures where the ceramic grains are the precursors of the macromolecules.Analysis of EPR signals for polymer-ceramic nanocomposites showed that Cu2+(I), as it follows from curves 1-4 of 1Ba2Cu3O0.67 ceramic grains and elements of the polymer chains. Such an interaction can be explained by the intercalation of some elements or fragments of the macromolecules into the layered structure of the ceramic. During such an intercalation, superposition of the unpaired electron of the Cu2+(I) x2-y23d orbital with the orbital of corresponding elements of the polymer chains occurs. As a result, the Cu2+(I) EPR response is altered because of the change of the valence state of Cu2+(I).Addition of polymer changes the valence state of Cu2+(I) EPR signal is dependent on the filling rate, e.g., on the fraction of binder in the ceramic. To answer this question polymer-ceramic nanocomposites were investigated with various Y1Ba2Cu3O6.97:SHMPE ratios: 100:0; 99:1; 97:3; 95:5; 93:7; 90:10; and 80:20 (in accordance to their mass %). The obtained data are presented in vs. the pure ceramic (curve 1). Further increase of the binder content reduces the signal intensity .Obviously, it is interesting to elucidate whether the intensity of the CuDoping of some atoms into a ceramic’s lattice structure is one of the techniques presently used in the search for new SC ceramic nanocomposites in order to enhance the onset of the SC transition temperature. Therefore, using metal-complex polymers as binders is a possible method of regulation of both the critical transition temperature into the superconducting state and its width.4(H2O)2(MO3)2, with M = Mn, Co, Y, Cu, etc. could be used. A previous investigation showed that frontal polymerization of AAm complexes in the presence of super conducting ceramic is possible only within a limited temperature range.It is known that acrylamide (AAm) complexes of metal nitrates of the first transition group are able to polymerize at frontal regimes. The essence of frontal polymerization is in localized heating of the sample edge initiating the polymerization . The heaExperimentally it was shown that the lower temperature limit for carrying out the reaction (100 °C) is given by the stability of frontal polymerization upon propagation of vertical heat waves from up to down. This sharply reduces and limits the yield of nanocomposites. The upper temperature limit (200 °C) is determined by the thermal degradation of nitrate groups in the nanocomposites obtained.The influence of density, temperature and reactor diameter on the structure of heat waves, rate of front propagation, range of existence of steady-state regimes was investigated. Experimental results obtained at different temperatures and densities are summarized in limρ) and full melting of crystalline monomer. There are no wave regimes of frontal polymerization below curve 1, limρ >ρ and meltT ≥ T.Here, curve 2 is the domain of steady-state heat polymerization waves which is limited by the straight line corresponding to limiting packing of reaction media  is shifting towards higher temperatures compared to the initial ceramic, cT = 93 K, fT = 78 K. The SC onset increase reaches 1–3 K for cT and more than 5 K for fT. It is known from the literature that the Y1Ba2Cu3O7-x high-temperature SC ceramic exhibits an anti-ferromagnetic transition, e.g., transition into the spin glassy (vitrous) state before the transition into the SC state. Presumably, anti-ferromagnetic and high-temperature SC states are co-existing. Taking into account that Co, Ni, Mn are known as anti-ferromagnetic metals, which intercalate into the interstitial layers of the ceramic, causing the 3-D properties of the ceramic grains to change. That is why cT increases and the transition width decreases. This interpretation is supported by our data on the change of the valence state of Cu in polymer-ceramic nanocomposites.The results of the investigation of super conducting properties of Mn-, Co-, Ni-, Zn-containing polymer-ceramic nanocomposites are presented in 1Ba2Cu3O6.92 sample is practically stable over time and is strong in absolute value intensity line. Y1Ba2Cu3O6.97 specimen is oriented along (006) and this reflex is not changed in absolute value as the time passed on. Besides, Y2BaCuO5 semiconductor phase is identified (211)—2% in content. The texture in both of these specimens is controlled by the relative intensities of the peaks: (110), (103), (005), (014), (113), (006), (020), (200).The prevailing orientation of the crystallites on the (110) direction in the Y1Ba2Cu3O6.97 specimens are stable enough over time .As it is evident from the data of the cT by 1–1.5 °C, an increase of ΔcT and decrease of η. Presence of antioxidant (NG-2246) does not influence the stated characteristics. This kind of stated characteristics changes can be explained by the enhanced inclination of the ST-MMA copolymer binders towards destruction under the impact of ultraviolet radiation.As already stated, for the superconducting nanocomposites of ST with MMA copolymers, the aging process brings a decrease of cT during the aging of the polymer-ceramic nanocomposites based on the polyethylene matrix, similar investigations were carried out on the samples obtained by the gas-phase polymerization of ethylene in the presence of Y1Ba2Cu3O6.97 ceramics as well. For obtaining more substantial data on the elevation of etc.) without using polymerization catalysts on the surface.Catalytic properties of oxide ceramic-perovskites have been known for a long time ,40,41. N1Ba2Cu3O7-x ceramic’s grains and, in this case, the polymerization process may proceed in the presence of polymerization  co-catalysts.Presumably, the layered structure of the crystalline orthorhombic phase will allow coordinating ethylene (or other kinds of olefins) on the surface of the YcT from 46 K  up to 70 K , which does not depend on the formula of the composition, mid-temperature (m.cT), and comparatively high temperature (h.cT), which depend appreciably on the content of polyethylene in the nanocomposites. That is why three transition temperatures were indicated in the l.c Tm.c Th.cT accordingly.Three transition temperatures into the super conducting state were detected on the curves  of superA different degree of degradation of various fractions of the ceramic cause the transition into the super conducting state have a stepwise character and, accordingly, thus decreases the rate of intercalation in relation with the degree of amorphizition of the ceramic’s grain.h.c.T) as well as its width substantially depends upon the weight ratio of the components of the composition. As was already stated, the observed increase of the (h.c.T) and (h.c–Th.f.T), can be explained by the sufficient intercalation  of the separate fragments of the polyethylene or the co-catalyst - into the interstitial layer of the Y1Ba2Cu3O6.97 ceramic during the gas phase polymerization of the ethylene.It is interesting to note that the beginning of the high temperature transition , leading to formation of local nano-compositions.Presently, doping of some atoms into the ceramic’s lattice structure is one the ways of searching for new SC ceramic nanocomposites with enhanced SC transition temperature onset. Therefore, use of metal-complex polymers as binders is a possible method of regulation of both the critical transition temperature into the super conducting state and its width .4(H2O)2(MeO3)2  are used as metal-containing monomers for frontal polymerization experiments. Investigations showed that frontal polymerization of AAM complexes in the presence of superconducting ceramic only occurs in a definite temperature range. It was shown that the lower temperature limit (100 °C) of the reaction is due to the stability of the polymerization front upon propagation of vertical heat waves from up to down. This sharply reduces and limits the output of nanocomposites. The upper temperature limit (200 °C) is determined by heat degradation of nitrate groups in the nanocomposites obtained.It is known that acrylamide (AAM) complexes of first transition row metal nitrates are able to polymerize at frontal regimes. The essence of frontal polymerization is in localized heating of the sample edge initiating the polymerization. The heat evolved (by the heat-conductance mechanism) is transmitted to neighboring layers, where the polymerization begins. The heat wave front propagates throughout the entire volume. Complexes of formula (AAM)1Ba2Cu3O7-x ceramic  does not allow frontal regimes to travel from top to bottom. At the same time, the formation of propagating frontal regimes of heat waves is observed at temperatures above 60 °C, when the wave is initiated from the bottom and the front propagates from bottom to up. This situation is explicable by the gas evolution during frontal polymerization, as well as by the inhibition of some constituents of the evolved gases on the polymerization process.Up to 100 °C, addition of minute quantities of YcT) is shifted towards higher temperatures, compared to the initial ceramic of cT = 93 K, fT = 78 K. This cT onset elevation amounts to 1–3 degrees, and fT —more than 5 degrees.The results of the investigation of super conducting properties of Mn, Co, Zn, Ni-containing polymer-ceramic nanocomposites are given in 1Ba2Cu3O7-x high-temperature super conducting ceramic undergoes an anti-ferromagnetic transition into a spin glassy state before the transition into the superconducting state. Moreover, it is presumed that anti-ferromagnetic and high-temperature superconducting states are co-existing. Taken into account that Co, Mn, Zn, Ni, are known as anti-ferromagnetic metals, which intercalate into the interstitial layers of the ceramic, this causes the 3-D properties of the ceramic’s grain to change. That is why cT elevates and transition width decreases. This explanation is supported by our data on the change of valence state of Cu in polymer-ceramic nanocomposites.It is known from literature that YcT increases by 1–3 K while SC transition width narrows down of to 4–6 K. There are no reasonable explanations for this fact.Samples of metal containing SC polymer-ceramic nanocomposites with various metal polymers were investigated on aging. The results of measurements of SC characteristics of nanocomposites before and after aging in the course of 1 year are given in Tc (by 1–3 K) of the composites versus the initial ceramic.Interaction of the elements of the macromolecule of the binder with the surface of the ceramic with further intercalation of these elements into the interstitial layer of the ceramic, thus causing some elevation of Stability of the polymeric binder against thermo-oxidative destruction, and, possibly, by the mechanism of disintegration of macromolecule . The possible participation of the oxygen from the orthorhombic phase of the ceramic in the processes of thermo-oxidative destruction of the matrix conditions broadening of the temperature interval of superconducting transition.Thus, on the basis of the obtained data in on the nature of the change of physical–mechanical and SC properties of the high temperature superconducting nanocomposites depending on granulometric composition and filling degree, it can be concluded that the peculiarities of forming the boundary of interstitial layer, oxide highly conductive ceramic–binder, its structure and adhesion of the binder with the surface of the ceramic play a significant role in the formation of superconducting and physical–mechanical properties of the obtained nanocomposites. For the nanocomposites mentioned an increase of melting heats has been found. This can be explained by intercalation of fragments of the macromolecules into the interstitial layer of the ceramics’ grains. This phenomena leads to the change of the morphological structure of the superconducting nanocomposites obtained. The latter has been proved by electron microscopy.2+ (1) are sound proof of the presence of intercalated fragments of the macromolecules into the interlayer space of the ceramic grains, leading to the formation of nanostructures.The ceramic-binder boundary plays an important role in superconductive and mechanic properties of SC polymer ceramic nanocomposites based on SHMPE. Thus, according to the data on dynamic mechanical properties, obtained over a wide temperature interval, it can be concluded that the peculiarities of the formation of the interface within the ceramic-binder boundary is most important. The data on electron microscopy and EPR signals on Cu1Ba2Cu3O6.97 ceramics grains’ surface allows using them as catalysts of olefin gas phase polymerization. Metal monomer frontal polymerization at the presence of Y1Ba2Cu3O6.97 ceramics allows preparation of metal containing polymer-ceramic SC nanocomposites.Thus, the activation of YIn conclusion, it can be stated that superconducting characteristics of the polymer–ceramic composites are determined by two main competing factors:The results of SC polymer-ceramic nanocomposites aging show that at room temperatures the intercalation of macromolecules fragments which are binding the interlayer space of ceramics takes place. This process results in formation intercalated nanostructures in the grains of ceramics.


The synchronized introduction of the inactivated polio vaccine (IPV) and the switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) has constituted an effort without precedents, and with astonishing results. Within the established time frame, all countries in our region managed to carry out the decision, planning, and introduction of this vaccine and subsequent switch to their national immunization schedules.The purpose of this article is to systematize the process of IPV introduction and switch in Latin America and the Caribbean, which constitutes an important piece in the documentation of the polio legacy in the Americas. Regional level as well as country perspectives and viewpoints are described. Analyzing and summarizing the lessons learned from the introduction of IPV and the switch from tOPV to bOPV can be useful for the introduction of new vaccines in the Pan American Health Organization (PAHO) region and in other regions of the world, and to help our own region successfully carry out another synchronized vaccine introduction in the future, if necessary. The purpose of this article is to share the experience of IPV introduction and switch in Latin America and the Caribbean. We conducted a descriptive analysis of PAHO support to countries for IPV introduction and the switch from tOPV to bOPV, and present the main findings on the countries experience around IPV introduction and the switch. This information constitutes an important piece in the documentation of the polio legacy in the Americas.Worldwide, sustained use of polio vaccines has led to a precipitous drop in the global incidence of poliomyelitis by over 99%, and the number of countries with endemic polio dropped from 125 to just 3  in 2016, when only 28 cases were reported as of November [The Region of the Americas (AMR) was the first region of the World Health Organization (WHO) to establish the goal to eradicate polio and to achieve polio elimination. The last case of this disease caused by wild poliovirus in the AMR was detected in 1991 in Peru, and in 1994 the AMR was declared polio-free .Following polio control in the AMR, in 1988 the 41st World Health Assembly (WHA) adopted the global goal to eliminate polio by the year 2000 . By 2010Unlike previous plans, the Endgame Plan anticipates the eradication of all poliovirus: wild, vaccine-derived poliovirus, and Sabin virus. To do this, the use of oral polio vaccine (OPV) must be phased out. This phased withdrawal began in April 2016 with the global switch from the trivalent oral polio vaccine (tOPV), containing all 3 types of poliovirus, to the bivalent oral polio vaccine (bOPV), containing only types 1 and 3 , 11.In order to ensure continued immunity against poliovirus type 2 after the switch, it was recommended that all countries introduce at least 1 dose of the inactivated poliovirus vaccine (IPV) before the switch , 13.The Pan American Health Organization (PAHO) Technical Advisory Group of Immunization (TAG) supported the renewed polio eradication efforts and the endgame eradication goals, including the introduction of at least 1 dose of IPV and the eventual withdrawal of OPV from routine vaccination programs. However, different than the other WHO regions, the TAG recommended IPV as the first dose, in a sequential schedule of IPV followed by OPV, based on the epidemiology of the AMR , 15. ThiPrior to 2013, 32 countries in the AMR only had an OPV schedule. Between early 2015 and early 2016, all of these countries were able to introduce at least 1 dose of IPV into their routine schedules before the switch, and between 17 April and 1 May 2016, 36 countries in the AMR participated in the global switch from tOPV to bOPV.Based on TAG’s recommendation and the urgency of the IPV introduction and the switch, PAHO developed a comprehensive technical cooperation strategy, including several virtual and face-to-face meetings and the development and adaptation of support documents to maximize chances of a successful regional IPV introduction and switch. PAHO also maintained permanent and close contact with the countries, with absolute availability for communications and country missions as requested. By the first quarter of 2015, PAHO had received the formal commitment from all Latin America and the Caribbean countries for the introduction of IPV.PAHO IPV Introduction Practical Guide [To promote the implementation of uniform technical guidelines, training materials and communication messages across the AMR, PAHO developed the al Guide  and adapal Guide .  and National Certification Committees (NCCs). Additionally, PAHO provided significant direct technical cooperation, including visits to selected countries, to ensure preparedness and avoid any switch delays.The remarkable success for the introduction of IPV and the switch in the AMR would not have been possible without the support from many international and regional partners. The support received from partners such as WHO Headquarters, UNICEF, CDC, the Task Force for Global Health, and GAVI was critical throughout the entire process of IPV introduction and the switch. These agencies provided valuable support to the AMR, including technical and/or financial support for the decision-making, planning, preparation, implementation, and validation of IPV introduction and the switch. The UNICEF Regional Office for Latin America and the Caribbean played a role in advocacy, social mobilization, and switch preparation and validation.Financial support from multiple international sources was channeled through GAVI and GPEI for some countries. These funds supported gaps in the national budget for IPV introduction and the switch, principally for coordination, planning and preparation, social mobilization, advocacy, trainings, human resources, and evaluation. Additionally, some countries reported having received technical and financial support from other partners, such as the Rotary Club, that played an important role advocating for IPV introduction and participating in the independent monitoring of the switch.Prior to the decision to introduce IPV in the AMR, the BMGF conducted an immunological study of 1 dose of IPV in Chile, and WHO supported studies of OPV-IPV in Cuba, which served as a key pieces of evidence to support the decision-making process in the AMR.In the PAHO Region, 19 countries and territories, representing 70% of the birth cohort in the AMR, were already using the IPV vaccine in their national schedule prior to 2015. The remaining 32 countries, representing 30% of the birth cohort in the AMR (4606700) introduced IPV as part of the Endgame Plan, between 2015 (22 countries) and the first half of 2016  team complete and return the survey to PAHO within 1 month.Thirty-one out of the 32 countries replied to the survey. Each country’s answers were read individually in their original language to become familiar with the perceptions of each country before coding. Key ideas were highlighted for each response. Once all responses were received, read, and translated to English, a matrix was created, which listed the questions in rows and each country’s response in columns.Some countries mentioned the same topic multiple times in different answers of their survey. In an effort to avoid swaying the results for the important facilitators and barriers in the AMR, a table was created where countries were counted only once, independent of how many times they mentioned the same topic in their survey response.A summary of the results is presented in this section  took 6 months or less to make the decision to introduce IPV, and an impressive amount of 17/31 countries (56%) took 1 to 3 months .The immunization program alone initiated the decision-making process in half of the countries (15/31), and in the other half (14/31), both the immunization program and the Ministry of Health coinitiated the process. Not surprisingly, almost all respondent countries (29/31) referred that the Ministry of Health authorities had the final say in the decision of introducing IPV. Only 3/31 countries said that the Presidency and/or Ministry of Finance were involved in the final say.It is noteworthy that, even though there was a WHA mandate to introduce the vaccine and a Regional TAG recommendation endorsing the introduction, countries still felt the need to consult their National Immunization Technical Advisory Group (NITAG). Fourteen of the 17 non-island countries involved their NITAG in the process, whereas the Caribbean discussed the issue at their EPI managers meeting, which resulted in a subregional endorsement of the introduction of IPV and the switch.Surprisingly, the majority of the countries (21/31) did not record any difficulties in the decision-making process. Only 4 countries mentioned financial issues as a complication in the decision-making process.Global commitment was the most frequently mentioned facilitating factor for the decision to introduce IPV (29%), followed by national political support and commitment (19%), the presence of a regional TAG recommendation (16%), and the availability of supporting evidence around the rationale for the introduction (13%).The decision to introduce IPV had coverage in almost half the countries (14/31), with radio being the most popular medium followed by newspaper and television. Many countries that announced the decision in the media received a positive media opinion (9/14 countries), whereas in a few countries, either the media expressed concern about adding 1 more shot to the well-child visit (3/14 countries) or had a neutral opinion about the introduction (2/14 countries).Two-thirds of the countries (20/31) did not need to make changes to their EPI infrastructure in preparation for the introduction of IPV, while one-third (11/31) needed to make changes. The changes that were required included expanding the cold chain (6/11 countries) and updating the immunization records and report forms to include IPV (4/11 countries). One country did not specify the changes required.In order to prepare health-care workers for the introduction, all countries (31/31) used face-to-face trainings, and most (29/31) used printed materials as well. Additionally, one-third of the countries also conducted virtual meetings, and a few used other strategies, including teleconferences .Twenty-five of 31 countries introduced IPV simultaneously nationwide, while 6 countries introduced it in phases. Countries with phased introduction were: Barbados, Bolivia, Guyana, Haiti, St. Kitts, and Suriname.For two-thirds of the countries (22/31), the introduction meant that children started to receive more than 2 injectable vaccines in a single visit.Several countries (7/31) mentioned the Ministry of Health and the professional associations (6/31) as national entities that provided support to the decision-making process and introduction of IPV. Additionally, 24/31 countries mentioned PAHO and 12/31 mentioned other international and regional entities that provided support, including financial support.The general public received information through the radio (16/31 countries) and printed communication (13/31 countries), as well as television communications (7/31 countries) about the introduction of IPV. An overwhelming 77% (24/31 countries) replied that they did not perceive any challenges to communicate the introduction of IPV, and of the 7 who did mention challenges, 4 countries said that it was related to the change in IPV administration from a drop to a shot.The public had a positive reaction to the introduction in two-thirds of the countries (22/31), with 9 of these countries expressing that the public had initial concern but after the communication efforts had embraced the change.Overall, the dominant themes within the facilitators were: commitment, engagement or buy-in from the different stakeholders, and knowledge. The support that PAHO provided to countries, either through technical cooperation or dissemination of guidelines and other materials, was the single most prominent facilitator for the regional introduction of IPV, mentioned by over two-thirds of the countries (23/31 countries). Other important positive factors were staff training (19/31); political will and support (17/31); commitment of staff (17/31); international commitment to the need for global IPV introduction to achieve polio eradication (14/31); and experience, preparedness, and planning of the EPI (13/31). Several other facilitators were mentioned.The majority of difficulties that were mentioned were unique to just 1 or 2 countries. The most common identified barrier for IPV introduction was the negative perception of the change in administration from drops to a shot (19/31). For most countries (23/31), the addition of IPV to the routine immunization schedule meant 3 or more injections at a single visit for a 2-month-old. Nonetheless, many of the countries that expressed this concern (9/31) also stated that after careful communication messaging and training of health-care workers, both the public and the staff felt reassured, and in the end, the public had a positive reaction to the introduction in two-thirds of the countries (22/31).Insufficient or delayed training was mentioned as the second most common difficulty (12/31 countries), which reinforces the notion that staff training played a pivotal role in the success of IPV introduction.Financial constraints were also expressed by 8/31 countries as a factor that hindered the IPV introduction process. Five countries were able to receive external financial support for IPV introduction, while the remaining 3 did not receive external financial support, but they still introduced the vaccine. This talks to the commitment of the countries of the AMR toward immunization in general, and more specifically toward polio elimination.Insufficient monitoring or supervision in the field was also mentioned by several countries (8/31), which prevented them from evaluating the successful implementation of the program.Ten out of the 31 countries did not mention anything that they would do different. The rest (21/31) replied with a variety of things they would change, including:Increase communication about the introduction to doctors in the private sector and to other stakeholders (6/31)Enhance supervision activities (5/31)Strengthen the training (4/31)Conduct earlier, better planning (3/31)Ninety percent of countries (28/31) used the IPV Introduction Guide provided to them, and almost all (27/31) said this was very useful. Ninety percent of the countries also used the background and technical rational documents, and 22/31 reported they were very useful as well. Around 70% of the countries used the training modules that were developed, and reported that they were also very useful.  Two-thirds of the countries (20/31) did not mention any type of support that would have been useful but was not provided, and the remaining 11 countries mentioned the need for more internal support, including PAHO country office being more present in the field (4/31), and more support for communication and dissemination (2/31).Thirty-six countries of the AMR switched from tOPV to bOPV in April 2016. In July 2016, PAHO administered a survey to these 36 countries through the same channels as the previous survey; all countries replied, and PAHO analyzed the information received using the same methodology previously described. Almost all countries (35/36) had national-level switch coordination committees, while 13/36 also had regional-level committees, 10/36 had departmental-level committees, and 8/36 had municipal-level committees. Some countries used subcommittees, including logistics, containment, surveillance, and communications, among others. Slightly less than half of the countries (14/36) used an already existing committee for this purpose.The most common departments of the Ministry of Health that were involved in the committee included Epidemiology (7), Public Health (6), and Surveillance (3), among others.Most countries (25) indicated that other ministries did not participate in the committee. Some countries indicated participation in the committee from the Ministries of Education, Agriculture, Finance, Natural Resources and Environment, Defense, Interior, and Labor.Twenty-three of 36 countries said there were actors from outside the government that participated in the committee, including private institutions and professionals, the Rotary club, professional associations, and universities and scientific societies, to name a few. Beyond participation in the committees, outside actors played a significant role in all stages of the switch process, including 19 countries that involved regional and international organizations, 10 that involved scientific societies, 6 that involved nongovernmental organizations (NGOs), and 3 that involved the Rotary Club.There were specific plans developed for a variety of activities, including training (35/36), bOPV delivery and distribution and tOPV withdrawal and destruction (33/36), supervision (29/36), communication (22/36) and information system (14/36) .All countries used face-to-face meetings as the main training methodology, but they also frequently used a mixed methodology for training, including virtual trainings and printed materials. Over two-thirds of the countries (27/36) used cascade training to train at the different levels. The training materials used were Microsoft PowerPoint presentations (36/36) and printed materials (29/36); one-third of the countries used videos (14/36).Almost half of the countries (17/36) made changes to their information system, to adapt it to the new schedule with the alerts and exceptions needed.Over half of the countries (20/36) implemented supplementary vaccination activities in preparation for the switch. Of these, most did these supplementary activities across the whole country (16/20).Twenty-four of the 36 countries had bOPV delivered to health facilities before switch day. Nine countries delivered bOPV on the switch day. Three countries only use OPV in their campaign, so prior to the switch they withdrew all tOPV and will introduce bOPV in the next national campaign.Twenty-nine of the 36 countries targeted different audiences with specific communication activities. Almost all countries targeted the health-care workers, and some countries also targeted parents and caregivers, the media, and the general public.Almost all countries (34/36) conducted briefings with key stakeholders, such as pediatricians, medical associations, NGOs, and so forth, in advance of the switch. Half of the countries (17/36) stated having organized media or public communication activities, such as press releases. Also, half of the countries (17/36) had a risk communication or crisis communication plan in place. The most common communication materials used by countries were posters or brochures (18/36), press releases (11/36), and radio spots (10/36).All 36 countries validated the switch through independent monitoring. Thirty of the 36 countries implemented the validation of 100% of warehouses and 10% of vaccination services within the recommended 15-day period following the national switch date, and submitted validation reports to PAHO; the other 6 countries were able to complete the validation of the switch after 15 days. After the validation period, all 36 countries completed supervision of the switch by visiting 100% of warehouses and vaccination services within 3 months of the switch date with their regular staff. All country reports were reviewed by the NCC, and subsequently by the RCC .During these visits to the 6132 warehouses, 50 (0.8%) warehouses were found with tOPV in the cold chain, and 11 (0. 2%) with tOPV not properly labelled outside the cold chain. The visits to the 98253 vaccination services found that 220 still had tOPV in the cold chain and 31 had tOPV not properly labelled out of the cold chain. In total, 5995247 doses of leftover tOPV were destroyed. The most common method of destruction was incineration. Ninety-five percent of all service points that use bOPV in the routine program had the vaccine available. This figure excludes Brazil, Cuba, and Mexico, because these countries only use bOPV in their campaigns. Ninety-seven percent of all service points in the AMR had IPV available. Of the 3% of service points that did not have IPV, 2.5% of this figure relates to 1 country that, at the time of the survey, had issues with IPV supply.Forty-two percent of the countries (15/36) replied that they did not encounter any obstacles in the planning process. Half of the countries that did encounter obstacles mentioned concomitant events as a factor that made the planning more difficult (11/21).Thirty-nine percent of the countries (14/36) did not mention any implementation obstacles of the switch. Vaccine transportation–related issues (7/36) were the most frequent obstacle mentioned.Finally, 30% of the countries (11/36) did not mention any obstacles in the validation process, whereas some countries mentioned insufficient financial resources to perform it (5/36) or reported delays in receiving the validation forms from a lower level (5/36).When asked how satisfied they were with PAHO’s support for the switch in general, all but 1 country replied. The 35 countries that replied had a positive view of PAHO’s support. Two-thirds of the respondent countries (21/35) considered PAHO’s support very good, and the remaining 14 countries considered it good. Countries that stated that the support from PAHO was “good” (and not “very good”) mentioned vaccine supply issues (3/14) and financial requests issues (2/14) as some of the problems faced with PAHO’s support.The types of support that PAHO provided for the switch that were mentioned most by countries were:Direct support to countries (25/36)Documents and materials (16/36)Countries were asked to rank different types of PAHO support by degree of importance. The guidelines and supporting documents received were deemed the most important type of PAHO support for the switch (20/36), and regional face-to-face meetings were the next most important PAHO support provided (12/36).Despite some manifestations of concern with the timeline and the budget required, the countries of the AMR always maintained a positive and readiness attitude throughout this process. This is, in part, thanks to the countries’ commitment to immunization in general, but also due to a tremendous commitment to polio eradication in particular, which has a mystique in itself. Countries of the AMR feel ownership and pride about polio eradication and want to see the end of this story.One of the most critical points for the success of this unprecedented worldwide and regional effort was ensuring that the countries understood the rationale and scientific basis for the decision to introduce IPV and make the switch from tOPV to bOPV, and the risk if this did not occur.Other facilitators were the experience of the AMR on new vaccine introduction, the experience with multiple injections in a single visit , and the experience of several countries in the AMR with introduction and use of IPV.Additionally, the PAHO Revolving Fund for Vaccine Procurement (RF), a cooperation mechanism for the joint procurement of vaccines, syringes, and related supplies, was a game changer for the AMR, because most countries (98%) readily accepted the vaccines without having to go through a special country registration as long as they are procured through the RF, so this had a positive impact in the introduction of IPV and bOPV.With regard to challenges faced in the AMR, the problems with the global vaccine supply and vaccine delays were major obstacles that had to be dealt with both at regional and national levels. A sense of Pan Americanism  played an important role when the global vaccine shortage did not allow for countries to introduce more than 1 dose of IPV, and PAHO had to recommend all countries who were not already using IPV to introduce a single dose. Other challenges included the fact that some countries with a more centralized government had more difficulty in making the decision.Finally, the global structure to support the regions played a crucial role in the AMR. As mentioned previously, the coordinated work of the partners, specifically through the work of the IMG, provided enormous support to countries throughout the whole process for both IPV introduction and the switch from tOPV to bOPV.In the history of vaccine introductions, there has never been a vaccine that had to be introduced by so many countries in such a short time frame. Additionally, the simultaneous switch from tOPV to bOPV was a unique and unprecedented event in global public health history. Overall, what seemed impossible ended up being possible thanks to country ownership of the polio eradication goals, and the excellent coordination and contribution of all partners.


Ischemia-reperfusion (I/R) injury is a well-known phenomenon that involves different pathophysiological processes. Connection in diverse systems of survival brings about cellular dysfunction or even apoptosis. One of the survival systems of the cells, to the assault caused by ischemia, is the activation of the renin-angiotensin-aldosterone system , which is focused on activating diverse signaling pathways to favor adaptation to the decrease in metabolic supports caused by the hypoxia. In trying to adapt to the I/R event, great changes occur that unchain cellular dysfunction with the capacity to lead to cell death, which translates into a poor prognosis due to the progression of dysfunction of the cellular activity. The search for the understanding of the diverse therapeutic alternatives in molecular coupling could favor the prognosis and evolution of patients who are subject to the I/R process. The ischemia-reperfusion injury (I/R) is a phenomenon that occurs after the restriction of blood supply to the tissues or organs . Abrupt The renin-angiotensin-aldosterone system (RAAS) is activated locally in the injured cells by the occurrence of I/R which plays an important role in the fate of the injured tissue, as characterized by an increase in stress that the tissue suffers during the assault, and changes caused by I/R lead to changes in the processes of adaptation in the cells subjected to hypoxia . The proThe standardization and administration of therapies focused on this system in the late phase of the I/R injury could prevent harmful changes to the affected tissues or organs, improving the prognosis, evolution, and sequelae of the injury process. In this review, we will describe the understanding of the possible mechanisms that unchain activation of the system in I/R injury and the possible therapeutic targets to diminish or prevent sequelae from I/R injury due to the pathological activation of oxidative stress, mitochondrial dysfunction, and autophagy.The I/R injury is an event characterized by multiple physiological components, both early and late . The RAARenin is an aspartyl protease glycoprotein enzyme that catalyses the restrictive excision of the angiotensinogen (AGT) to angiotensin I (Ang I), an essential component within the processes of the system's activation . The ren+ and Cl−), and (c) the activation of β1-adrenergic receptors (autonomous system and circulating catecholamines) [β) and the epidermal growth factor (EGF), by the activation of survival proteins, hypoxia, stress signals, or unspecific phosphorylation of the membrane receptors like the Ang, tyrosine kinase, and β-adrenergic [1R receptors, β1-adrenergic receptors, adenosine, and prostaglandins and the presence of low concentrations of Ca++. However, the gene also has other promoters for expression as an element of response to hormones, the nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription (STAT), that also stimulate renin expression, which will be expressed more avidly during the initial and late phase of the I/R injury [There are three classic and principal mechanisms of control in the liberation of renin: (a) the activation of glomerular baroreceptors (changes in the diameter of arterioles), (b) the activation of glomerular chemoreceptors or macula densa  . The aculamines) . Differerenergic . This kirenergic . The prorenergic . The renR injury .The AGT is a glycoprotein and serine protease inhibitor that belongs to the superfamily of the inhibitory serpins. The AGT gene is located on the chromosome 1q42-43 and contains 5 exons and 4 introns with more than 12 kb. The AGT has a receptor site for cAMP and is sensitive to activation by the steroid receptor and elements of response to cellular stress . The AGT1R and AT2R that are involved in the signaling pathways of survival, cell division, differentiation, the vasopressor effect, hypertrophy, and the modulation of oxidative stress in the I/R process [2R receptor, the MAS, and the Ang type 7 receptor (AT7R). Even, the RAAS system links the mitochondrial pathways in the treatment of I/R-induced injury in cardiac cells because activation of the Ang 1-7/MAS receptor could be a possible adjunct to ischemic preconditioning during cardiac injury induced by I/R [Ang I interacts with two enzymes that are similar to each other, the angiotensin-converting enzyme (ACE) and the angiotensin-converting enzyme type 2 (ACE-2) , 19. The process , 21. The process . Ang II,d by I/R –25.The secretion of Ang is regulated locally in the affected tissues on being transformed in the plasma by circulating renin and the production of Ang I in the tissues and later of Ang II , 27. Mor1R and the AT2R that favor the phosphorylation of the PKC [κB and the mitogen-activated protein kinase (MAPK) that the cell suffers during the initial phase of injury, which leads to the unspecific expression of genes that condition the phenotypical change of the cell in the production of enzymes and the proteins mediated by the TGFβ and signaling pathways of the SMAD proteins [Aldosterone is a steroid hormone and a mineralocorticoid with the most influence in mammals on the control of fluids and electrolytes , 33. The the PKC . The tra the PKC . They ar the PKC , 47. All the PKC . Transcrproteins , 50 , the prorenin receptor, the MAS receptor (MASR), and the MET (METR) receptor; the last of which has an activity mediated by the insulin-regulated aminopeptidase receptor (IRAP) [++ and mediated by calmodulin that is necessary for the coupling and activation of the G protein [1R-AT1R) or as heterodimers  located in the cellular membrane, physiologically, or in states of stress of the same cell, modulating multiple signaling pathways through direct activation of the receptor or by indirect activation or inactivation of the paired receptor [Injury from activation of the RAAS system in the acute phase is characterized by a mechanism of adaptation to the assault, and as the event of I/R is established, the genes involved are overexpressed in maintaining the adaptation, unchaining the substitution of injured tissue with fibrous tissue, changes in the function or phenotype of the cell , hypertrophy, cell division, or apoptosis , 51. Ther (IRAP) , 53. Ther (IRAP) , 54. Ther (IRAP) . C-termi protein . Activat protein , 56. Thereceptor   proteins can couple secondarily to the proteins Gi/o, G12/13, and Gs or the class of Rho, Ras, and Rac [1R (1R during I/R injury produces the modulation of ion channels through the activity of the beta-gamma complex of the G protein (Gβγ) with the production of ROS by activation of the NADPH oxidase enzyme complex, cellular differentiation through activation of the signaling of MAPK, PI3K, and JAK-STAT, and fibrosis through activation of the RTK that promotes differentiation, activation, and proliferation of fibroblasts that will suffer activation of the metalloproteinases coupled with the membrane (ADAM and MMP) [κB factor and STAT [Specifically to the AT and Rac . The sig Rac [1R  is also and MMP) . Hypertrand STAT  . However, studies where they have achieved designs of the tridimensional structure  demonstrate that the receptor has an intracellular section in the H8 domain that, depending on its position, favors or impedes the coupling of what could be the G protein or the bond with β-arrestin for it to be internalized [2R receptor can dimerize with the bradykinin receptor (B2R) in the cell membrane and with the mtNOS in the mitochondrial matrix, which, on activation, increase the production of NO in the two microenvironments [−) [2R-AT1R produces direct inhibition of the AT1R receptor. Another mechanism of action described for the AT2R is the activation of phosphatases  that dephosphorylate the signaling pathways activated by the AT1R and are activated by the RTKs, MAPK, JAK/SATA, and ERK1/ERK2, which bring the inhibition of cellular proliferation and differentiation, activation of fibroblasts, and activation of the proapoptotic pathways [2R also reduces inflammation by inactivation of the signaling pathway mediated by RTKs that activate through phosphorylation of the inhibitor IKκB of the NF-κB, decreasing the concentrations of IL-6 and other proinflammatory cytokines [The ATrnalized . It has ronments , 61. Whients [−) , 63. Thients [−) , 65. Thepathways . The actytokines .β1, the monocyte chemoattractant protein 1 (MCP1), the connective tissue growth factor (CTGF), and the plasminogen activator inhibitor type 1 (PAI-1). The MR has the ability to activate the NADPH oxidase anchored in the cell membrane, increasing the formation of oxidative stress that leads to the activation of the signaling pathways and the accumulation of extracellular matrix that produces hypertrophy, fibrosis, and alterations in the stability and activity of ion channels [The mineralocorticoid receptor (MR) is a nuclear receptor that contains 984 amino acids with three functional domains, an extreme N-terminal activation function domain (AF-1), a middle DNA-binding domain (DBD), and a C-terminal ligand-binding domain (LBD) . Activatchannels , 70. It channels , 70.β receptor, which brings about fibrosis and cellular proliferation. During the phenomenon of I/R, the receptors' expression and activity are increased, which signifies their critical role in perpetuation of the I/R injury in the long term [The prorenin receptor  has 350 ong term .2−), the hydrogen peroxide (H2O2), and the hydroxyl radical (OH·), whose fundamental characteristic is based on exceeding the antioxidant defenses. There are several enzyme systems that contribute to the formation of ROS, including the NADPH oxidase, the xanthine oxidase, and the leakage of mitochondrial electrons of the mitochondrial electron transport chain (METC). The ROS are normally generated as a natural by-product of oxygen metabolism and play an important role in cell signaling. However, when ROS levels augment dramatically under pathologic conditions such as cardiac insufficiency, I/R, and aging, oxidative stress is produced [2− anion. Ang II facilitates the uncoupling of the NOS through the increase in the production of the O2− anion, and the uncoupled NOS additionally increases levels of the O2− anion in the vasculature and accelerates endothelial dysfunction. Hence, Ang II is considered a potent activator of the NADPH oxidase. The ROS derived from the NADPH oxidase promote the generation of ROS from the mitochondria [1 receptor blockers is efficacious in reducing the reperfusion damage caused by myocardial ischemia. Losartan is an AT1 receptor blocker that was initially introduced for its hypotensive action, although other studies have demonstrated that, apart from its hemodynamic effects, it could have cardioprotective influences directly affecting the myocardiocytes. Losartan is capable of augmenting the ventricular fibrillation threshold and decreasing the size of an infarct and of augmenting the number of premature cardiac beats, episodes of ventricular tachycardia, and the mortality rate [Oxidative stress is considered the state of disequilibrium between antioxidant defenses and the excessive production of ROS, among which are the superoxide anion (Oproduced . The NADproduced . The mitchondria . The clichondria . Therefoity rate . Nonetheity rate .The sirtuins (SIRT1–SIRT7) are a class of proteins that are characterized by the deacetylation of the histones and a wide range of nonhistone proteins such as enzymes and transcription factors. The sirtuins undertake a fundamental role in the regulation of biological cell activities like metabolism, cell death, cell growth, and the cellular responses to oxidative stress . Sirtuin++ levels [2O2, and the modulation of apoptosis [2− anion [2− anion is liberated from the mitochondrial matrix and from the mitochondrial intermembrane space where it is converted into H2O2 by the MnSOD and the copper-zinc superoxide dismutase (CuZnSOD) [2O2 can be detoxified to water through the action of the mitochondrial enzyme glutathione peroxidase (GPx) or to water and oxygen by the catalase by the cardiac mitochondria. These enzymes belong to a complex, multilevel system of mitochondrial defense, composed of nonenzymatic antioxidant enzymes that participate in the detoxification of ROS [− anion that is formed when the O2− and the NO react. Thus, the mitochondria are relevant formulators of ROS and RNS, which leads to mitochondrial dysfunction with alteration to the generation of energy (ATP) on augmenting the generation of ROS [The mitochondria are energy-producing organelles that carry out diverse, key cellular functions including the regulation of the cytosolic Ca+ levels  and the + levels , 86, thepoptosis   . The H2On of ROS . The mitn of ROS .1 receptor blockers reduce mitochondrial dysfunction related to age, attenuate the renal mitochondrial dysfunction induced by hypertension, and protect against cardiac mitochondrial dysfunction from acute ischemia [1 receptor [1 receptor blockers of Ang II in patients with arterial hypertension, cardiovascular illness, and diabetes mellitus seem to be partly [1 receptor blockers of Ang II can exert direct effects on the tissues in addition to the hemodynamic effects. In this sense, the RAAS inhibitors act effectively against oxidative stress and mitochondrial dysfunction [Ang II stimulates mitochondrial dysfunction in the cardiac smooth muscle, kidney, and vascular cells . Inhibitischemia . The mitischemia . In studischemia . In the ischemia . The immreceptor . The rene partly  independe partly . That sufunction . There afunction .κB and c-Jun. If these mechanisms are insufficient to alleviate the misfolded protein load, the ERS activates the immune response against cellular stress and promotes cell death by apoptosis or necrosis [++ overload of the ER lumen, which in turn modulates the mitochondrial vulnerability of Ca++ and apoptosis, favoring the release of cytochrome c and the activation of caspases. Once ER homeostasis has been exacerbated, new expanded proteins accumulate and UPR is activated. This occurs during the cold storage of the graft in preservation solutions. UPR/ERS alterations increase after reperfusion, which are determinants for the graft result after transplantation [The ER is an important intracellular organelle responsible for the synthesis, folding, and trafficking of a wide variety of proteins, hormones, enzymes, receptors, ion channels, and transporters. In normal situations, there is homeostatic equilibrium between the inflow of displayed peptides and the folding capacity in the ER. However, when unfolded or misfolded proteins accumulate, ER stress (ERS) occurs and a specific adaptive response of the cells is triggered to prevent the abnormal accumulation of unfolding proteins. The ERS activates intracellular signal transduction pathways that together are known as the unfolded protein response (UPR) . The UPRnecrosis . The injnecrosis . Becausenecrosis . The insantation . On the antation .++ to cells through two components; the difference in the concentration of Ca++ in the extracellular fluids , in addition to the electrical potential through the plasma membranes. The interior of the plasma membrane is 60–90 mV, and for the outside, the value is negative. The electrochemical potential is maintained because the Ca++ fluxes associated with signal transduction are small and tightly regulated and because the increase in Ca++ triggers the extrusion of Ca++ by the exchange of 3Na+-Ca++ and by a Ca++-2H+ exchanger driven by ATP. The leakage ratio of the pump maintains Ca++ at values of 100–200 nmol/L, although the concentration increases transiently during the activation of the cell [++ enters the cell through multiple pathways; additional channels can even be opened under adverse conditions, for example, nonspecific cation channels and others activated by ROS as per H2O2. However, in the depolarization and accumulation of intracellular Na+, the 3Na+-Ca++ exchanger is able to operate in reverse mode, which causes Ca++ to accumulate in the cell [++  are approximately 0.1 and 1000 μmol/L, respectively. However, the total content of cellular Ca++ (excluding extracellular spaces) is approximately 1000 μmol/L ; it is deduced that >99% of the total cellular Ca++ content is found bound to proteins or phospholipids or sequestered in the ER in the calciosomes and mitochondria. Although the source of the increase in Ca++ is often due to extracellular Ca++, the cell contains enough Ca++. The uncontrolled release of Ca++ predisposes to cell damage [++ decreases to values < 10% approximately 0.1 mmol/L, and the extracellular fluid decreases to ~50% of the control. This means that almost all extracellular Ca++ is translocated to cells. With an extracellular fluid of 20% tissue volume and an extracellular Ca++ of ~1.3 mmol/L, the load of Ca++ to which the cells are exposed is ~250 μmol/kg of tissue. Since it is unlikely that much Ca++ uptake will occur in the cells, the Ca++ load could double that number, which means that the total Ca++ content of the cells can increase to ≥150% of the control. Long-term focal ischemia leads to pan necrosis and death of all cell types [++ from extracellular fluids to intracellular fluids and that reperfusion restored extracellular Ca++ to normal in 15–20 min, without knowing whether changes occurred in the total content of Ca++ in tissues [++ in parts of the brain after 24 h of reperfusion [++ content [++ correlating it with microscopic data of cell death and found that the total content of tissue Ca++ during reperfusion increased between 24 and 48 h and that the increase in intracellular Ca++ apparently preceded the morphological signs of cell death [There is a large driving electrochemical force that tends to translocate Cathe cell . Ca++ enthe cell . The conl damage . During ll types . Therefoll types . In the  tissues , 118. Inerfusion . The hig content . Based oll death .α/TNFR1). The receptor-ligand interactions result in the grouping of receptors and the recruitment and oligomerization of adapter proteins (FADD to the Fas receptor). Following the recruitment and oligomerization of FADD, procaspase-8 binds to FADD through the dimerization of its effector death domain resulting in the formation of the death-inducing signaling complex (DISC) and the autocatalytic activation of the caspase-8. The activation of caspase-8 triggers the execution phase of apoptosis [++ overload, and overproduction of ROS [Apoptosis regulates cell turnover in healthy living organisms by eliminating excessive or unhealthy cells. Apoptosis plays a fundamental role in the development of tissues and aging. The apoptotic process consists of two main pathways, the death receptor pathway (extrinsic pathway) and the mitochondrial pathway (intrinsic) –124. Thepoptosis . The intpoptosis . The extpoptosis , 128. Inpoptosis . In I/R n of ROS .Macroautophagy  is the nonselective multistep process through which portions of the cytoplasm and/or organelles are isolated in vesicular structures that include mitochondria (mitophagy) known as autophagosomes. The autophagosome fuses with the lysosomes and degrades the autophagosomic contents.Microautophagy occurs when the cytosolic load is isolated directly in the lysosome through engulfment of the lysosomal membrane.Chaperone-mediated autophagy (CMA) occurs when the misfolded proteins of the cytosol are degraded .Autophagy is a highly conserved process of bulk protein degradation, responsible for the rotation and clearance of proteins and the elimination of organelles . Autopha1 receptor induces the excessive production of ROS and unchains autophagy, senescence, and apoptosis in the myocardiocytes and smooth muscle cells. However, if the activity of the RAAS rises, there are benefits with the use of ACE inhibitors or AT1 receptor blockers in diabetic patients without cardiovascular complications, although this fact remains controversial [An efficient flow through the autophagy pathway is essential for cell survival . The freoversial .1R at the onset of the injury is necessary for the cells or injured tissue to have the capacity to survive the ischemic assault. However, the subsequent pathological activation of these receptors during the early phase of I/R injury and the overactivation of the signaling pathways and the genes involved will lead to the epithelial-mesenchymal transition, fibrosis, hypertrophy, and cellular proliferation. For this reason, it is important to understand that blocking the signaling pathways in the ischemic phase will likely not improve the evolution of the initial injury, yet modulation of the signaling pathways in the subsequent phases will favor the limitation of damage and can probably reverse it Based on what has been observed, the activation of the signaling pathways for AT2− anion and of the uncoupled NOS, increasing the levels of the O2− anion in the vasculature, and accelerating endothelial dysfunction. The mitochondria play a critical role in the cellular responses to a great variety of stimuli. The mitochondria receive, integrate, and transmit signals and activate metabolic processes and the processes of adaptation. Mitochondrial damage can lead to dysfunction of the organelle with alterations in the functioning of the tissues. Ang II stimulates mitochondrial dysfunction in the cells of cardiac smooth muscle and kidney and vascular cells, and its inhibition decreases the liberation of mitochondrial ROS, augmenting efficiency of the METC, protecting the mitochondrial structures, and favoring the production of ATP. The local concentration of Ang II in the kidney is, it seems, greater than systemic levels of Ang II. Treatments for the regulation of the RAAS are well known, such as the ARBs, ACEI, renin inhibitors, MR inhibitors, and inhibitors of aldosterone and antioxidant production; yet, despite being able to rely on this number of drugs, the dosage and standardization of a regimen for the management of I/R injury have still not been established. The recommendation would be to start the medications based on an understanding of the physiological processes of the I/R injury and activation of the RAAS. The end result is not to block the response entirely but rather to modulate the exaggerated response of the RAAS when faced with I/R injury.The elements of the RAAS are considered potent activators of the NADPH oxidase: the ROS derived from the NADPH oxidase promote the generation of ROS from the mitochondria. Ang II and the other active metabolites facilitate the uncoupling of the NOS, favoring an increase in the production of the O