Survey questionnaire.
\r\n\tRisk management aims to develop an efficient organizational development environment through risk planning, assessment, analysis, and control. This process will apply in all areas of activity, and the evaluation framework is the same regardless of the field. This volume will aim to appeal to chapters that address methods, models, evaluation frameworks, benefits, barriers, and other dimensions of risk management.
\r\n\tSustainability and the circular economy are approaches approached by many companies and have become activities of global interest. Protecting the environment, streamlining the consumption of organizational resources, reducing the amount of waste generated, and other activities are objectives of these efforts. The circular economy contributes to the sustainable development of the company or country and the achievement of the global objectives of sustainable development. This book will aim to collect various studies for organizational and global sustainability.
\r\n\tLeadership has become a globally desirable approach that can help improve organizational competitiveness and reduce organizational risks. Risks and barriers in risk-free management can be well managed through effective organizational leadership. This book will aim to bring together chapters that explore different areas of leadership.
The present chapter uses the SERVQUA model to identify the gaps between customer satisfaction and the needs of logistics service users by determining the relationship between customer satisfaction and targeted actions to manage the risk of dissatisfaction by logistics service providers.
The essence of the methodology used is based on the following model assumptions:
Expectations and perceptions of the logistics services studied must at least match to obtain a positive assessment of quality from users of the service.
In cases where there is a discrepancy between the target and actual values of the surveyed services, the quality score will be negative.
Based on strategic discrepancies between target and actual values (system discrepancies) in quality, the reasons for the insufficiency of the measured service quality values are analyzed.
Opportunities to identify discrepancies are related to:
Customer perceptions: Mismatch between customer expectations and perceptions of the management of the service received in a real environment.
Senior management perceptions: Mismatch between the perception of the service provider’s senior management and customer expectations of the proposed service quality specifications.
Process execution: Mismatch between service quality specifications and actual performance.
Communication with customers: Inconsistency between the service and the message addressed to the customer about the service.
The survey was first conducted as a pilot online survey to test the feasibility of the questionnaire from 1 December 2020 to 1 January 2021. The pilot survey covered 15 respondents who were mailed the evaluation questionnaire. The results of the pilot survey showed that all the respondents understood all the questions.
The baseline survey was conducted through a questionnaire and included a sample of 115 respondents, who were required to have experience in managing logistics processes. The survey was conducted from 15 February 2021 to 15 April 2021. A total of 105 questionnaires were collected, of which 100 were valid (5 of the questionnaires were not completed correctly and some of the questions had more than one answer), with a response rate of 95%. The survey was conducted directly through a telephone interview or internet communication depending on the suitability of the respondents. The valid questionnaires were collected from 52 logistics service providers and 48 customers.
The model used to conduct the chapter on customer satisfaction with logistics services contains seven latent variables. The antecedents of logistics service satisfaction are customer expectations of logistics service, perceived quality, perceived value, and image. While the two indicators of the consequences of satisfaction are: nonconformities (complaints, returns) and loyalty.
The latent variables were defined using manifest variables appropriate for the purposes of this chapter and were measured in the survey. Associations between manifest and latent variables are described using a set of equations with unknown coefficients.
The following latent variables and hypotheses were investigated and analyzed in this chapter:
Expectation: Two indicators were studied. Customer expectations related to logistics service culture. The manifestation of expectations depends on how customers perceive and interpret the factors influencing the formation of expectations. Various factors are under the control of the company and depend on the performance of logistics services, while others depend entirely on customer perceptions (psychological, cultural, and social). Therefore, the quality of feedback and personal contact with employees have the potential to create value and should be a priority. Sales staff need to understand customer perceptions before guiding them to the appropriate choice of product for order preparation. The indicator relates to the provision of a correct logistics service, the speed of response, and the ability of customer-facing staff to make timely decisions on the disposal of a nonconforming product.
The expectation hypothesis: Customers’ expectations of the services have a positive impact on the quality of the service provided and an indirect positive impact on overall satisfaction.
Quality: Five indicators of the expected quality of logistics services were studied. Logistics service quality is the extent to which the set of inherent service characteristics satisfies the requirements of customers and stakeholders1.
The hypothesis (Quality) that logistics service quality has a priority and positive impact on overall satisfaction was tested during the data analysis.
Value: Two indicators of perceived value were investigated. The perceived value of logistics services motivates the customer to tradeoff between the quality received versus the price paid to acquire the service. The service that customers receive at the time of purchase influences the perceived value.
The hypothesis (Value) that customer perceived value has a positive impact on overall satisfaction with logistics services was tested during the data analysis.
Image: The indicator refers to the good reputation and image of the logistics company or the ability of the service provider to inspire trust and confidence. The positive impact of this factor is achieved by measuring satisfaction through various means that provide tangibility to the logistics service and service culture including tangible items relating to the facility, environment, and all types of hardware and equipment required to provide services.
The hypothesis (Image) that customers’ perceived image positively impacts expectations, overall satisfaction, and loyalty for logistics services was tested during the data analysis of the chapter.
Satisfaction: Three satisfaction indicators were studied. The satisfaction indicator is related to the customer’s reaction to the comparison between the expected and actual experience of the logistics service. An essential condition for achieving good financial performance lies in finding a way to minimize the differences between the expected and actual experience of the logistics service.
Complaints: Customer discrepancies (customer complaints) that arise while providing logistics services that are unfulfilled as expected or actual customer requirements. Complaints should be used to improve any process in which a nonconformance is identified.
Loyalty: Customer loyalty is the customer’s positive attitude towards the logistics service provided because of factors that are significant to the customer.
The questionnaire required each survey participant to rate the margin of acceptability of the quality of logistics services on a 5-point scale (0 points – does not meet customer requirements and 5 points – fully meets and exceeds requirements. In cases where respondents’ perceptions did not match the two extremes of the rating, they could select any number between 1 and 5 to rate how strong their expectations and perceptions were. The accompanying instructions explicitly stated that the purpose of the survey was not to find acceptable or unacceptable responses but only to establish the exact numerical rating that reflected their opinion of the quality of the logistics service and their level of satisfaction as its users.
The survey questionnaire is shown in Table 1.
Rate the statements on a 5-point scale: (1) completely disagree (2) disagree (3) hesitate (4) agree (5) completely agree | ||
---|---|---|
Indicator | Questions to respondents | Evaluation |
Expectation | PLSE1. The knowledge and experience of the nominated contact person are sufficient to understand the problems encountered | 1 □ 2 □ 3 □ 4 □ 5 □ |
PLSE2. Problems arising are resolved by the designated contact person | 1 □ 2 □ 3 □ 4 □ 5 □ | |
Quality | PLSQ1. Ordering procedures are easy to use | 1 □ 2 □ 3 □ 4 □ 5 □ |
PLSQ2. Shipments rarely contain incorrect quantity | 1 □ 2 □ 3 □ 4 □ 5 □ | |
PLSQ3. Supplies arrive on the promised delivery date | 1 □ 2 □ 3 □ 4 □ 5 □ | |
PLSQ4. Shipments rarely contain defective products | 1 □ 2 □ 3 □ 4 □ 5 □ | |
PLSQ5. The manner in which claims are settled is adequate | 1 □ 2 □ 3 □ 4 □ 5 □ | |
Value | PLSV1. Logistics services meet the requirements (specifications) | 1 □ 2 □ 3 □ 4 □ 5 □ |
PLSV1. Logistics services are reliable and on time | 1 □ 2 □ 3 □ 4 □ 5 □ | |
Image | PLSI1. Complaints are rarely due to the method of transportation | 1 □ 2 □ 3 □ 4 □ 5 □ |
PLSI2. No difficulties have ever arisen due to lack of availability | 1 □ 2 □ 3 □ 4 □ 5 □ | |
PLSI3. The time between placing the order and receiving the delivery is short | 1 □ 2 □ 3 □ 4 □ 5 □ | |
PLSI4. Product return procedures are easy to use | 1 □ 2 □ 3 □ 4 □ 5 □ | |
PLSI5. The resulting products are not normally crushed damaged | 1 □ 2 □ 3 □ 4 □ 5 □ | |
Satisfaction | PLSS1. Logistics services to meet your expectations in number and scope | 1 □ 2 □ 3 □ 4 □ 5 □ |
PLSS2. Selected logistics services are the right choice | 1 □ 2 □ 3 □ 4 □ 5 □ | |
PLSS3. I am satisfied with the overall logistics service | 1 □ 2 □ 3 □ 4 □ 5 □ | |
Complaint | PLSC1. The corrective actions taken following complaints are adequate for the problem encountered | 1 □ 2 □ 3 □ 4 □ 5 □ |
PLSC2. Corrective actions taken following complaints are timely | 1 □ 2 □ 3 □ 4 □ 5 □ | |
Loyalty | PLSL1 I would recommend the logistics services used | 1 □ 2 □ 3 □ 4 □ 5 □ |
PLSL2 I would use logistics services in the long-term | 1 □ 2 □ 3 □ 4 □ 5 □ |
Survey questionnaire.
Tenenhaus and Michel’s [1] study built based on the SERVQUA methodology provides the reference for the possible and expected model of interaction between the variables that would be obtained based on the results of the study (Figure 1).
Key attributes of the causal model describe the causes and consequences of customer satisfaction. Source [
The partial least squares modeling method was used to analyze the data obtained from the survey measuring the identified gaps between satisfaction and needs of the logistics service user customers. Multivariate analyses (partial least squares path-modeling [PLS-PM]) were performed to simultaneously assess the potential relationships between different logistics service quality and satisfaction indicators. An appropriate analysis method was selected after investigating a convenient tool to examine the multiple relationships (latent variables) of variables (factors).
The PLS-PM model reflects causal relationships with arrows that start in a latent variable (factor) and point to measured indicator variables. The PLS-PM was chosen as the most convenient tool to examine relationships between observed and unobserved (latent) variables. Matrices in which 15–20% of the data are missing or have experimental errors can be processed by the PLS-PM method.
The possible outcomes of the PLS-PM study are presented in Table 2.
Outcome interpretation in PLS-PM models (multivariate analysis).
Through the assessment method, the relationship between variables acting on a particular outcome through multiple causal pathways is examined. Data processing was done using XLSTAT software [2] for modeling PLS relationships (pathways) implemented in the XLSTAT statistical analysis package of Microsoft Excel. The built-in XLSTAT-PLSPM interface [2] allows to build of a graphical representation of the model and to display results in Excel as tables or graphical images. XLSTAT-PLSPM is fully integrated with the XLSTAT package and allows different survey data analyses to be performed with other XLSTAT applications.
The main objective of the risk analysis of noncompliant processes in logistics services is to identify, assess, and forecast the significant factors that affect the prosperity and development of logistics companies. The fulfillment of this objective is accomplished through the method:
Analysis of types of refusals and their consequences - Failure mode and effects analysis (FMEA). The method is defined and standardized by experts. After the expert team that has the necessary experience and knowledge of the object under study has been assembled, the methodology identifies and ranks the logistics risks under study. Irrespective of the ranking method, it is necessary to identify each logistics risk-specific program and actions to eliminate or minimize the negative impact.
The method applies to various fields of knowledge [3] but it is not known to have been applied to analyze the risks of nonconforming processes related to satisfaction in logistics services. This made it necessary to develop and apply a new methodology to assess nonconforming processes in logistics services, as one of the tasks for this chapter. The chapter investigates the risk in logistics processes that may contribute to the deterioration of satisfaction indicators in logistics services related to FMCG and, specifically, the food sector.
The methodology is essentially based on the following model assumptions:
Detecting nonconforming logistics processes at a late-stage leads to higher costs for the company.
The strategy of detecting and correcting nonconforming logistics processes can be replaced by the strategy to avoid them and eliminate the causes in the planning phase.
The costs of controlling and tracking nonconforming logistics processes in the stages immediately preceding the physical delivery of goods can be minimized.
The experience gained from noncompliant logistics processes can be used to address the cause of their reoccurrence in the future.
The principle of error prevention should be prioritized in managing nonconforming logistics processes.
Quality control of logistics services should be assigned to highly competent employees who play a role in the actual execution of the processes.
Limitations in the application of the method are related to the control over its management and can be defined in three main directions:
The control of the risk of noncompliant logistics services is specific to each market segment and may impair its objectivity.
Despite the measures to control the risks and to neutralize the negative impact of some factors, the developed methodology cannot completely eliminate the impact of all random factors.
Although the analysis is based on real risks, the achievement of the residual risk values, after the implementation of the control measures, may not be fully consistent with the actual outcome given the influence of unknown factors in the assessment.
Control measures need to be implemented for fully measurable outcomes of noncompliant logistics processes and those that cannot be measured with complete accuracy.
The proposed control measures to manage the risks must be adapted to extreme changes in the external and internal environment.
In establishing the Risk Priority Number (RPN) and its three components of Severity (S), Likelihood (O), and Detection (D), the assessment of the degree of risk assigned by the experts conducting the analysis can be highly subjective.
The analysis based on expert opinion must also assess whether the three parameters are equally important. In cases where the experts judge that this is not the case, significance coefficients should be assigned to each of the components (S), (O), and (D).
It should be considered that each factor requires different preventive actions to prevent or minimize the risk of a negative impact of the error or noncompliance occurring even in cases where the analysis results in identical RPN scores for different factors.
To apply the method, a separate RPN (Risk Priority Number) must be determined for each process.
The numerical value of the RPN denoted the quantification of the risk that caused the nonconformity in the logistics service obtained as the product of the probability of the nonconformity occurring, the probability of the nonconformity being detected before the customers, and the severity of the impact in case it is not detected. The values for each of the RPN components can range from 1 to 10 as indicated in Table 3, determination of RPN risk class Table 4.
(S) Severity of consequences | (O) Probability of occurrence | (D) Probability of detection |
---|---|---|
8–10 A small change in the risk factor can make a significant difference in satisfaction with logistics services. | 8–10 The risk factor is expected to have a negative impact on satisfaction | 7–10 The possibility of detecting noncompliance before it affects satisfaction is negligible |
5–7 A small change in the risk factor has the potential to significantly affect satisfaction with logistics services. | 5–7 Significant likelihood that the risk factor will negatively impact satisfaction | 4–6 There is little possibility of detecting noncompliance before it affects satisfaction |
2–4 Changes in the risk factor have only a marginal impact on satisfaction with logistics services. | 2–4 Risk factors unlikely to negatively impact satisfaction | 2–3 The opportunity to identify noncompliance before it affects satisfaction is significant |
1 Changes in the risk factor do not affect satisfaction with logistics services. | 1 Negligible likelihood that the risk factor will negatively impact satisfaction | 1 The discrepancy can be detected before it affects satisfaction |
Determination of RPN components.
Value of RPN | Explanatory notes |
---|---|
RPN over 851 Very high-risk | The potential consequences of noncompliance can cause dissatisfaction, increase the churn of current and potential customers, and significantly degrade the performance metrics of the logistics services that are important to the customer. |
RPN 600–850 High risk | The potential consequences of noncompliance can significantly degrade the satisfaction and performance metrics of logistics services that are important to the customer. |
RPN 150 to 599 Moderate risk | The potential risk of noncompliance is likely to negatively impact satisfaction and degrade performance metrics for logistics services that are important to the customer to a moderate degree. |
RPN up to 149 Low risk | A low-risk class is defined when the potential consequences of noncompliance will result in a temporary reduction in satisfaction. |
RPN up to 10 Negligible risk | A negligible class is defined when the potential consequences of the noncompliance occurring will have no impact on the company’s operations and customer satisfaction. |
Determination of RPN risk class.
A pilot study was first brainstormed and conducted to test the feasibility of applying the FMEA method to analyze the risk of noncompliant logistics services related to customer satisfaction from 1 May 2020 to 15 May 2021. The pilot study was conducted with five leading logistics professionals and its results showed that all participants support the application of the FMEA method for analyzing logistics processes. Each participant in the pilot study was required to be an employed logistics manager with at least five years of experience in the field and demonstrated competence through the submission of diplomas and certificates.
The baseline survey was conducted through discussion and brainstorming from 01 June 2021 to 01 September 2021. A total of nine team meetings were held to assess the risk of noncompliant logistics processes using the FMEA method. The analysis team included 10 participants and one moderator. Each participant satisfied the criteria as an employed logistics manager (logistics as part of a manufacturing site or logistics services as an independent company) and had proven competence through the presentation of diplomas and certificates. The moderator took notes on the discussion based on which the main highlights of the participants’ opinions were extracted.
The consensus was reached in the team meetings by following the steps outlined in Figure 2.
Consensus model for risk analysis of noncompliant processes in logistics services.
The method was used, based on the results obtained from the survey on customer satisfaction using the SERVQUA method conducted in the period from 15 February 2021 to 15 April 2021, to analyze possible inconsistencies and errors in the implementation of logistics processes and identify their causes and consequences. Within the framework of quality management in logistics, FMEA has been applied to enhance customer satisfaction and reliability of logistics services to prevent their nonconformance.
Potential system deficiencies are evaluated based on their significance to the customer, the likelihood of their occurrence, and the ability to detect and correct the nonconformity before losses or consequences are incurred. The method can be used to analyze not only planned but also actual processes where the risk of changes and the impact of these changes on the management of logistics activities must be assessed.
The essential advantages of the method are related to uncovering opportunities and adopting a quality management approach through risk management. The method implies performing analyses that enable a collaborative management approach within the logistics organization. In this way, quality management can be oriented towards the risks generated by dynamic changes in the external and internal environment, which are often the root cause of nonconformities in the system. Essential priorities of quality management in logistics should be the realization that quality deficits increase losses and the corporate philosophy must be changed to bring the quality management system back under the control of the logistics organization. The goal is to understand and accept that impeccable service can only be achieved through sustainable compliance and improvement. The purpose of risk analysis is to identify and promptly address gaps in the service delivery system that negatively impact customer satisfaction.
The FMEA determines the likelihood of these gaps occurring and their potential consequences by assessing, in terms of severity, the measures required to prevent the risk, their effectiveness in specific situations, and the residual risk in the event of system failures. In cases where the method is adopted as a corporate philosophy in decision-making for new service offerings, risks of compromised quality should be identified and mitigated in accordance with the principles for applying the method.
The methodology to analyze and summarize the results of the study conducted on the risk of nonconforming processes is based on the Pareto analysis. The tool is named in honor of the Italian economist Pareto, who is also its creator [4]. In 1897, after annually analyzing the distribution of wealth in Italy, Pareto found that the incomes in the public were unequally distributed [5, 6]. The Pareto principle, also known as the 80/20 rule, states [7] that, for many events, approximately 20% of the causes contributing to 80% of the effect [8]; therefore, which are unequally distributed. The method can be applied after the significant causes of inconsistencies in the system are identified and analyzed, and losses will be minimized by eliminating them.
The method classifies quality problems in logistics services into two areas – few but essential and numerous but minor problems. This and other methods in quality management must be based on reliable information gathered from specific logistics services applied in practice. The data should reflect real events from economic processes that need to be analyzed and processed further. The analysis appropriately targets problem-solving efforts and identifies the main drivers of nonconformities. Juran interprets this principle by establishing that 20% of the causes of product defects create 80% of product problems.
The Pareto analysis was conducted simultaneously with the risk assessment of noncompliant logistics processes using the FMEA method and the same sample. The obtained data on the ex-ante and residual risk identified by the FMEA method were compared in the Pareto analysis procedure.
The values for upfront and residual risk from noncompliant logistics processes were tabulated in the procedure and the team assigned a percentage to each value such that the total was 100%. The percentages assigned were then used to construct a bar chart.
The Pareto analysis identified the differences in the ranking of causes before and after the implementation of corrective actions to the noncompliant logistics processes. The resulting diagrams have practical implications and can be used by senior management of logistics firms to prioritize actions and minimize risk.
XLSTAT software, which is embedded in Microsoft Excel’s XLSTAT statistical analysis package, was used in conducting the Pareto analysis.
The following N number of qualitative or quantitative values were awarded in the Pareto analysis of the sample identified in the FMEA risk assessment of noncompliant logistics processes:
Number of observations: The number N of values in the selected sample.
Number of missing values: The number of missing values in the sample that are ignored in subsequent statistical calculations of the values.
Sum of weights (Sw): The sum of the weights awarded, considering that all weights are equal to 1, Sw = n.
Mode: The mode of the sample analyzed is the most common category.
Mode frequency: The frequency of the category to which the mode corresponds.
Category: The names of the different categories present in the sample.
Relative frequency by category: The relative frequency of each category.
Cumulative relative frequency by category: The cumulative relative frequency of each category.
Methods are also applied to analyze, systematize and differentiate various requirements that form satisfaction and help manage the quality of logistics services.
All the principles and methods of building management systems and the comparative analysis between different objects are also applied in the study. In addition to the listed main methods, the principles of quality and risk management required by the international standard ISO 9000:2015 and ISO 31000 have been applied.
The methods used in the chapter have the potential to help achieve its main objective and define the chapter design and the methods of data collection and analysis.
Due to the increasing market competition, a necessary condition for increasing customer satisfaction is the provision of qualified services that help organize timely deliveries of the goods requested by the customer. Through process controls, these processes could help to prevent nonconforming services from occurring prior to customer requirements.
The chapter of the study describes the conceptual framework of two groups of methods 1. Methodology for conducting the SERVQUA Satisfaction Analysis Survey (CAP) in Logistics and 2. Methodology for conducting the risk analysis study of noncompliant processes in logistics services. All the principles and methods of building management systems and the comparative analysis between different objects are also applied in the chapter. In addition to the listed main methods, the principles of quality and risk management required by the international standard ISO 9000: 2015 and ISO 31000 have been applied. The methods used in the chapter have the potential to help achieve its main objective and define the study design and the methods of data collection and analysis.
Hemophilia is a disease that has a frequency of approximately 1 in 10,000 births. It has an X-linked transmission, and it consists in a bleeding disorder due to the deficiency of clotting factor VIII (hemophilia A) or factor IX (hemophilia B). Hemophilia is a genetic or acquired disease that leads to spontaneous and recurrent bleedings, which affect the joints and muscles, thus determining chronic damage to the cartilage which will lead to joint disease and hemophilic arthropathy.
There are two major types of hemophilia: type A and type B. These disorders are X-linked and consist in hemorrhages, resulting from diminished levels of clotting factors VIII and IX. Type A is 5–6 times more frequent than type B. This pathology affects in a symptomatic manner only male patients and is characterized by excessive bleeding, which is installed rather spontaneously or after minimal incidents, and is difficult to stop [1].
Hemophilia is a chronic condition that requires a substitution treatment with the defective factor. Its severity varies accordingly to the residual factor level. It is classified as severe (when the clotting factor activity is less than 1%), moderate (1–5%), and mild (6–40%).
If not treated hemophilic patients, especially those with very low clotting factor activity and severe disease, have recurrent disabling and life-threatening bleeding episodes. Using prophylactic factor therapy may diminish bleeding; therefore these novel therapies have changed the prognosis of hemophilic patients, providing increased life expectancy and better quality of life [2, 3, 4].
Even though hemophilic patients were initially thought to have a low incidence of atherothrombotic complications, it is now clear that atherothrombotic events occur.
Limited data suggest that hemophilia is not protective against atherosclerosis and thrombosis, but this theory is still to be studied in men with severe forms of hemophilia without other CVD risk factors, such as active HIV infection [5].
The most common manifestation of hemophilia is represented by bleeding. The severity of hemorrhages is correlated with the plasmatic level of clotting factors. Therefore, there are patients with mild or minor hemophilia that may not bleed excessively until they undergo a surgical intervention or after a trauma.
The accurate diagnostic of hemophilia is mandatory for an optimal management. Hemophilia should be suspected in patients with early bruising in childhood, with excessive hemorrhages after trauma or surgical intervention, or in patients with spontaneous bleeding.
Patients with hemophilia need a complex therapeutical management. The most important aim is to administrate the deficient clotting factor so that bleedings are terminated or prevented. If an acute bleeding occurs, it is important to treat it in the first 2 hours.
In order to ease the appropriate management, all patients should carry upon them accessible identification information such as diagnosis, severity of bleeding disorder, type of treatment product that should be used, and contact information.
The patients with hemophilia should benefit from a comprehensive care treatment provided by a team of specialists. This type of care should increase the quality of life while reducing morbidity and mortality.
Hemophilic patients should benefit from fitness and physical activity therapy, in order to obtain normal neuromuscular development, coordination, healthy body weight, and appropriate self-esteem [6].
Adjunctive therapy should be provided consisting in physiotherapy, antifibrinolytic drugs, and certain COX-2 inhibitors in order to soothe the pain.
Prophylactic factor replacement therapy should be administrated so that bleeding and joint destruction is prevented, thus preserving a normal musculoskeletal function.
Surgery is required for complications related to hemophilia or for unrelated disease. The surgical treatment should be done in a comprehensive treatment center for hemophilia [7, 8].
In the majority of cases (90%), the bleeding episodes in hemophilic patients occur in the joints, thus leading to hemarthrosis. From all these bleedings, the most affected joints are the knees, elbows, and ankles. The affected articulation is usually swollen, held in flexion, the mobility being very restricted and painful.
If the deficient clotting factor is given quickly, the hemorrhages can be controlled, and the episode can benefit from conservative orthopedic treatment without long-term complications.
If the bleeding persists or if hemorrhages reoccur, the presence of blood in the joint may lead to apoptosis of the chondrocytes. When there is too much blood present, the synovial membrane will become hypertrophic as it tries to reabsorb the blood. From that moment a vicious circle of chronic synovitis develops thus leading to join destruction and to hemophilic arthropathy [9, 10] (Figure 1).
Modifications of hemarthrosis in hemophilia [
The hypertrophic synovial membrane consists of villous formation with increased vascularization and chronic inflammatory process. Hemophilic children will have hypertrophic epiphyseal growth plates. This bone hypertrophy can determine length discrepancies and modifications in contour and angular deformities. Further destruction of the cartilage may appear if the inflammatory and hemorrhagic process is not controlled. When the synoviocytes are destroyed, they release lysosomal enzymes that promote further cartilage destruction and promote chronic inflammation. As the modifications progressively occur and the cartilage of the joint degrades, the joint function diminishes, and there are limited and painful movements [12, 13, 14].
The apparition of hemarthrosis is the most frequent and unfavorable clinical expression of a hemorrhage in a hemophilic patient; it has an incidence of 75%. It usually appears between 1 and 5 years; if it does occur after 10 years, it is usually due to a mitigated condition. The other symptoms that may appear are relapses. The trigger is represented by a trauma which is very frequently unnoticeable. The most affected joints are in a decreasing order as follows: knees (36%), ankle (30%), elbow (23%), hand (6%), shoulder (3%), and hip (2%) [15, 16].
Hemarthrosis usually affects only one joint, but sometimes the bleeding may be present in both joints, but the lesions are not symmetric. Relapses usually affect the same articulation. Each bleeding episode determines disorders of the joint, thus creating a predisposition for a relapse. The joint structures will weaken, the muscles become atrophic and develop fibrosis thus the join functionality becomes mechanics deficient. In order to bleed less, the synovial will become hypertrophic and will have an increased vascularization, and this mechanism will lead to a vicious circle. From this moment on, a chronic condition begins and is called “hemophilic arthropathy.” This complication advances slowly during time and induces severe modification of the joint with ankylosis. Some experimental studies have proven that a major hemarthrosis induces in the cavity of the joint a dense inflammatory process, while the local tissues change their color and become brownish as a result of the hemosiderin deposits that are due to the erythrocyte damage. The vessels become hyperplasic, thus creating brittle vessels, which are prone to bleeding, therefore inducing a vicious circle: bleeding-vascular hyperplasia-bleeding [11, 17, 18].
The surface of the articulation roughens and pannus is formed. The bone located in the subchondral region becomes dysmorphic. After 30 days the erosions present in the cartilage and bone are obvious.
Different studies have proven that the affected joints are an important factor in inducing cartilage destruction in hemophilic patients. Different authors showed that the presence of iron in the intra-articular blood induces molecular modifications that can offer an explanation for the cellular proliferation in the synovial membrane (synovitis).
Valentino et al. proved in an experimental study that the bleeding that results from a controlled trauma causes joint swelling, synovitis, and hemophilic arthropathy.
In order to alleviate these complications, substitutive treatment with deficient coagulation factor applied from a young age (primary prophylaxis) represents the best therapeutic conduct. Even though primary prophylaxy with the deficient clotting factor is given despite, some patients still have intra-articular hemorrhages, as a result of an insufficient dose of coagulation factor or due to a diminished adherence to the therapy, while other hemophilic patients may present sub-clinically manifested hemarthroses [19, 20].
If continuous prophylactic therapy with clotting factors is provided, the natural course of the arthropathy can be slowed down. One of the most threatening complications of the therapy with clotting factors is the apparition of alloantibodies that are directed against the exogenous molecules of clotting factor. This complication appears in one third of the patients, and it increases the likelihood to develop an uncontrolled bleeding [20, 21].
There has been a new drug developed for the treatment of hemophilic patients. It is called emicizumab, and it is a recombinant antibody that brings activated factor IXa and factor X into an adequate conformation that will lead to the activation of factor X and therefore will mimic the cofactor function of factor VIIIa. A subcutaneous injection with emicizumab that is given once weekly proves to be an efficient method to prevent bleeding in the majority of type A hemophilic patients with inhibitors to factor VIII. Even more the prevention of bleeding has been observed in 66% of patients without inhibitors to factor VIII.
The administration of plasmatic factor VIII has better clinical results in type A hemophilic patients than the transfusion with plasma. The side effects are linked to viral infections transmission such as hepatitis B, C, or HIV; therefore it is better to use in clinical practice recombinant clotting factors that are associated with a diminished risk of viral transmission. In order to have safer products, there have been more modern generations of recombinant factor VIII (rFVIII) developed, the viral transmission being much lower with each new generation of compounds. The first generation had a human serum albumin in order to stabilize the product. The second-generation compounds have no albumin in their composition, but proteins from humans or animals were still allowed in the process of cell culture. The third-generation compounds have eliminated animal and human proteins, but contain murine monoclonal antibodies, which are still used for the purification of rFVIII. It was proven that the elimination of the middle portion (domain B) of the wild-type FVIII did not diminish the clotting activity. It was also shown that the full-length protein had similar effects. These findings helped to discover the recombinant FVIII with deletion of the B domain called moroctocog alfa [21, 22].
ReFacto® is a recombinant clotting factor VIII which has a B-domain deletion (moroctocog alfa). It has a molecular weight of about 170,000 Da and contains1438 amino acids.
ReFacto has a similar functionality as endogenous clotting factor VIII. When given to a patient with hemophilia, factor VIII will bind to the patient’s intrinsic von Willebrand factor. When activated factor VIII becomes a cofactor for activated factor IX, thus catalyzing the activation of factor X. The activated factor X will subsequently transform prothrombin in thrombin. The latter will transform fibrinogen in fibrin, thus forming the red clot. When giving substitution treatment, the levels of factor VIII increase, and the deficiency is temporarily corrected, thus leading to a diminishment in bleeding episodes [1, 23].
We analyzed five patients with hemophilia type A, aged between 35 and 62 years. Two of them had a severe form of hemophilia with factor VIII less than 1%, while the other three had a moderate form with factor VIII ranging between 1 and 5%. All of them described intense pain as a result of functionally chronic knee arthropathies. Thus, the lesions had an indication of endoprosthesis and total knee repair. These orthopedic interventions were done by a multidisciplinary team, formed by hematologists, orthopedists, and intensive care staff (Figure 2).
TKR for severe hemophilic osteoarthritis.
The orthopedic surgeries were realized after a rigorous hematological control, offered through the national protocol for hemophilia. Therefore, all patients received the necessary amount of substation therapy with clotting factor. During the surgery and in the postprocedural surveillance period, the patients had their blood count, hemostasis, and transfusion requirements very thoroughly assessed. Also, other postsurgical complications were routinely searched (Figure 3).
(A–H) Severe axial deformity. Genu varum in severe hemophilic arthropathy. (A–B) Preoperative X-rays. (C–D) Severe genu varum clinically and radiologically. (E–F) Postoperative X-rays. (G–H) Clinical view of the knee with axis restored and wound healed.
The postsurgical evolution of these patients was favorable, with similar hemostatic profile as the non-hemophilic patients. Only one patient had increased bleeding times, as his clotting profile associated also a factor VII deficiency, thus requiring blood transfusion.
After the administration of Moroctocog alpha substitution treatment, all five patients had a normal clotting profile, thus requiring thromboprophylaxis with LMVH (enoxaparin) in order to prevent VTE. An important aspect to be noted refers to the fact that the amount of bleeding did not correlate with the levels of residual factor. Even more, we noted no differences regarding the volume of blood drained after the surgery between patients with moderate or severe hemophilia. The elderly patients had similar outcomes with young patients with favorable postoperative prognosis, consisting in diminishment of joint pain, improvement in functionality, and increased quality of life. We thus concluded that older age is not a contraindication for complex surgical intervention.
The systemic substitutive treatment was very efficient and normalized the clotting profile of the patients. Therefore, the surgical hemostasis was done without using topical agents such as bio surgical gels or foams. Even more the intrasurgical bleeding of these patients was similar with the hemorrhage seen in patients without the diagnosis of hemophilia. The monitorization of the clotting profile of the patients was thoroughly done by a hematologist trained in treating hemophilic patients requiring elective surgeries. The administration of the substitution therapy followed the guidelines described in the National Protocol of Hemophilia. The clotting profile was monitored daily, and the results showed a normal hemostasis after the administration of treatment. That is why we decided to give low-molecular-weight heparin in these patients, as the risk of thromboembolic events increased after the normalization of the hemostasis, due to the associated risk factors (age, sedentarism, obesity, cardiovascular disease). We chose to give enoxaparin once daily in a 1 mg/kg dose, and the clinical and paraclinical results were favorable.
Pruthi et al. published a paper in 2000 regarding the use of thrombophylaxy in patients with hemophilia. They presented the case of a patient with moderate hemophilia B, who underwent treatment with factor IX concentrate in order to realize a total hip replacement for a hip fracture and developed venous thromboembolism in the operated limb after the intervention. The thrombophilia screening detected the presence of a heterozygous type of factor V Leiden mutation [24]. Therefore, the authors concluded that presurgical screening for thrombophilia is useful in hemophilic patients who had a previous history of VTE. Another research realized by Mannucci the same year suggested that all patients with thrombophilia should receive short-term therapy with LMWH if they are exposed to significant risks such as prolonged immobilization or surgery [25].
Later in 2004, Dargaud et al. suggested that hemophilic patients should not routinely receive thromboprophylaxis as there are not enough studies, but they also added that hemophilia per se does not protect against venous thromboembolism. The conclusion of this study was that specific cases with increased risk of thrombosis should receive therapy with LMWH [26]. In 2006 Butcher and Pasi reported the case of a patient with hemophilia A, who developed an episode of massive pulmonary embolism after major pelvic surgery. Thus, they concluded that thromboprophylaxis in selected hemophilic patients is very important [27].
Another research done by Uprichard et al. in 2012 included 13 patients with total kidney replacement, from which 11 had hemophilia B. They received mechanical thromboprophylaxis, and one also received pharmacological treatment. The results were satisfying as no patient suffered VTE [28].
In 2012, Uprichard et al. analyzed a series of 13 TKRs in 11 patients with hemophilia B, who received mechanical thromboprophylaxis, and 1 also received pharmacological thromboprophylaxis. No patients suffered VTE [29].
On the other hand, another study realized by Krekeler et al. in 2012 analyzed 105 interventions, 90 of them being major orthopedic surgeries and 15 minor surgeries. The authors did not find any case of VTE even though therapy with LWMH wasn’t given after the surgery. In the same year Ozelo arrived as the same conclusion as Butcher and Pasi. Another research from 2013 done by Berntorp stated that in case of elderly patients diagnosed with hemophilia or patients with von Willebrand disease, a rigorous assessment of the risk and benefit of thromboprophylaxis in the patients who underwent major orthopedic surgery should be realized.
Ozelo et al. proved that the use of graduated compression stockings and early mobilization is sufficient in preventing VTE in the majority of patients. Thus, the administration of anticlotting therapies should be taken into account just for patients that have strong additional risk factors for thrombosis. Contrary, patients with hemophilia treated with inhibitors should not receive pharmacological thromboprophylaxis. Patients with von Willebrand disease, who receive replacement therapy with factor concentrates and who underwent surgical procedures, should have a strict monitorization of FVIII plasma levels, and thrombophylaxy should be taken into account if there are other thrombotic risk factors [30, 31, 32].
The best therapy for hemophilic patients consists in doing primary prophylaxy so joint bleeding and other complications are prevented. Even though orthopedic surgeries in these patients are associated with increased risk of complications such as infections and hemorrhages, they can increase significantly the joint mobility and life quality if they are realized in specialized centers with hematological support. Moroctocog alfa is an efficient substitutive treatment that manages to normalize the hemostatic profile of patients. Therefore, it is recommended to provide prophylactic antithrombotic therapy after the orthopedic interventions.
The Internet has irrevocably changed the dynamics of scholarly communication and publishing. Consequently, we find it necessary to indicate, unambiguously, our definition of what we consider to be a published scientific work.
",metaTitle:"Prior Publication Policy",metaDescription:"Prior Publication Policy",metaKeywords:null,canonicalURL:"/page/prior-publication-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\\n\\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\\n\\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\\n\\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\\n\\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\\n\\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\\n\\n1. CONFERENCE PAPERS & PRESENTATIONS
\\n\\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\\n\\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\\n\\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\\n\\n2. NEWSPAPER & MAGAZINE ARTICLES
\\n\\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\\n\\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\\n\\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\\n\\n3. GREY LITERATURE
\\n\\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\\n\\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\\n\\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\\n\\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\\n\\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\\n\\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
\\n\\nIn cases where there is any overlap between the Author´s submitted manuscript and related internet postings, we will generally not consider it to be an instance of self-plagiarism. This also holds true for any co-Author as well.
\\n\\nFor more information on this policy please contact permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-03-20
\\n"}]'},components:[{type:"htmlEditorComponent",content:'A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\n\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\n\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\n\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\n\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\n\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\n\n1. CONFERENCE PAPERS & PRESENTATIONS
\n\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\n\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\n\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\n\n2. NEWSPAPER & MAGAZINE ARTICLES
\n\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\n\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\n\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\n\n3. GREY LITERATURE
\n\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\n\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\n\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\n\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\n\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\n\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
\n\nIn cases where there is any overlap between the Author´s submitted manuscript and related internet postings, we will generally not consider it to be an instance of self-plagiarism. This also holds true for any co-Author as well.
\n\nFor more information on this policy please contact permissions@intechopen.com.
\n\nPolicy last updated: 2017-03-20
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Throughout the life cycle, many of them thrive in pathogen-rich environments, manage harsh weathers, exposed to a number of allochemicals, and adapt well to both terrestrial and marine ecosystems. Their remarkable ability to cope up with the enormous oxidative stress generated in all these circumstances, make them attractive models in this field of research. Endocrine control of oxidative stress in insects is recently emerging. Adipokinetic hormone, glucagon, ecdysteroids and juvenile hormone have been implicated in antioxidative protective role in insects. Drosophila and Caenorhabditis elegans have provided the largest body of evidence addressing the free radical theory of ageing. Oxidative stress is also induced by pesticides/insecticides. In mollusks, pesticides exert their biological effects via generation of ROS. Oxidative stress has been shown to be associated with exposure to several organophosphorous compounds and different classes of pyrethroids. Malathion is a potential hazard to the environment. Adverse effects induced by malathion in earthworms and insects have been reported. Information is now available in great detail on the role of ROS in modulating insect immunity during parasite invasion and bacterial infection. In Drosophila melanogaster ROS are actively produced in the midgut at a basal level in the presence of commensal microbiota and highly generated upon bacterial challenge. The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. The concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens. Elevated oxidative stress was previously reported for a mosquito line experimentally infected with Wolbachia, indicating that oxidative stress may be important for Wolbachia-mediated antiviral protection. In a nutshell, this chapter highlights the current advances of oxidative stress in invertebrate model systems and its implications.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"R.K. Chaitanya, K. Shashank and P. Sridevi",authors:[{id:"178087",title:"Dr.",name:"Rk",middleName:null,surname:"Chaitanya",slug:"rk-chaitanya",fullName:"Rk Chaitanya"}]},{id:"51874",doi:"10.5772/64700",title:"Ovarian Cancer Metastasis: A Unique Mechanism of Dissemination",slug:"ovarian-cancer-metastasis-a-unique-mechanism-of-dissemination",totalDownloads:3109,totalCrossrefCites:12,totalDimensionsCites:23,abstract:"Ovarian cancer is the most lethal of all gynecologic malignancies and has witnessed minimal improvements in patient outcomes in the past three decades. About 70% of ovarian cancer patients present with disseminated disease at the time of diagnosis. The standard of care remains a combination of debulking surgery and platinum‐ and taxanes‐based cytotoxic chemotherapy. Even though metastasis is the leading cause of ovarian cancer related fatalities, our understanding of the process remains limited. Ovarian cancer has a unique pattern of metastasis where the hematogenous spread is less common. Ovarian cancer cells mainly metastasize within the peritoneal cavity, which involves exfoliation from the primary tumor, survival, and transport in the peritoneal fluid followed by metastatic colonization of the organs within the peritoneal cavity. A key step for successful metastasis is their attachment and productive interactions with the mesothelial cells covering the metastatic organs for the establishment of metastatic tumors. This chapter provides an overview of ovarian cancer metastasis highlighting the unique dissemination and the underlying mechanisms of regulation of the steps involved. The role of the microenvironment in the process of metastasis will also be reviewed.",book:{id:"5267",slug:"tumor-metastasis",title:"Tumor Metastasis",fullTitle:"Tumor Metastasis"},signatures:"Anirban K. Mitra",authors:[{id:"185152",title:"Dr.",name:"Anirban",middleName:"Kumar",surname:"Mitra",slug:"anirban-mitra",fullName:"Anirban Mitra"}]},{id:"51903",doi:"10.5772/64787",title:"Role of Oxygen Free Radicals in Cancer Development and Treatment",slug:"role-of-oxygen-free-radicals-in-cancer-development-and-treatment",totalDownloads:3627,totalCrossrefCites:14,totalDimensionsCites:17,abstract:"It is well known that species derived from oxygen are cytotoxic and are involved in the etiology of cancer. Several carcinogens during metabolism exert their effect by producing reactive oxygen species (ROS). One of the consequences of oxidative damage to cellular DNA is mutated. It plays a vital role in the process of carcinogenesis (especially in the initiation and progression). The alters, including rearrangement of DNA sequence, base modification, DNA miscoding lesions, gene amplification, and the activation of oncogenes, could be implicated in the initiation stage of several cancers. Mitochondrial changes in the cancer cells are well known and as a result are respiratory injured. Mitochondrial dysfunction could lead to a low coupling efficiency of the mitochondrial electron transport chain (mETC), raising electron leakage and increased ROS formation. It has been documented that by reducing and inactivation of antioxidant system, the oxidative stress (OS) in cancer cells is higher. Cancer cells exhibit a higher oxidative stress level compared to normal cells, rendering tumor cells more vulnerable to raise ROS levels. Therefore, increasing ROS levels through redox modulation can be a strategy to selectively kill cancer cells but not normal cells. A promising anti-cancer method named “oxidation therapy” has been developed by causing cytotoxic oxidative stress for cancer therapy. In this chapter, we described the role of ROS as a double-edged sword in cancer development and treatment.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"Jalal Pourahmad, Ahmad Salimi and Enaytollah Seydi",authors:[{id:"172672",title:"Prof.",name:"Jalal",middleName:null,surname:"Pourahmad",slug:"jalal-pourahmad",fullName:"Jalal Pourahmad"}]},{id:"44689",doi:"10.5772/55415",title:"Drug Resistance and Molecular Cancer Therapy: Apoptosis Versus Autophagy",slug:"drug-resistance-and-molecular-cancer-therapy-apoptosis-versus-autophagy",totalDownloads:4010,totalCrossrefCites:2,totalDimensionsCites:14,abstract:null,book:{id:"2857",slug:"apoptosis",title:"Apoptosis",fullTitle:"Apoptosis"},signatures:"Rebecca T. Marquez, Bryan W. Tsao, Nicholas F. Faust and Liang Xu",authors:[{id:"19713",title:"Dr.",name:"Liang",middleName:null,surname:"Xu",slug:"liang-xu",fullName:"Liang Xu"},{id:"149902",title:"Dr.",name:"Rebecca",middleName:null,surname:"Marquez",slug:"rebecca-marquez",fullName:"Rebecca Marquez"}]},{id:"51890",doi:"10.5772/64569",title:"Oxidative Stress and Autophagy",slug:"oxidative-stress-and-autophagy",totalDownloads:1964,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"Free radical production related with many stress factors including radiation, drugs, ageing and trauma plays a key role in cell death. Notwithstanding, free radicals can cause pathology in a variety of diseases through oxidative stress: Under oxidative stress, excessive production of free radicals can trigger cell death by primarily DNA and all cellular macromolecule damages. Also, excessive free radicals have a role in early inducers of autophagy cell death upon nutrient deprivation. Autophagy is physiologic process of eukaryotic systems, which have significant role in adaptation to oxidative stress by degradation of metalloproteins and oxidatively damaged macromolecules. By oxidizing, membrane injuries allow the leakage of enzymes and contribute to cell damage. However, recent publications demonstrate the protecting role of lysosome system during excessive reactive oxygen species (ROS) production by the elimination of damaged proteins or organelles. Activation of autophagic or lysosomal system can eliminate the oxidizing components of cell in oxidative stress response. This chapter aims to provide the novel insight data for oxidative damage-mediated autophagy as well as their metabolic networks.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"Adem Kara, Semin Gedikli, Emin Sengul, Volkan Gelen and Seckin\nOzkanlar",authors:[{id:"177953",title:"Dr.",name:"Adem",middleName:null,surname:"Kara",slug:"adem-kara",fullName:"Adem Kara"},{id:"178363",title:"Dr.",name:"Emin",middleName:null,surname:"Sengul",slug:"emin-sengul",fullName:"Emin Sengul"},{id:"178365",title:"Dr.",name:"Semin",middleName:null,surname:"Gedikli",slug:"semin-gedikli",fullName:"Semin Gedikli"},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen"},{id:"178367",title:"Dr.",name:"Seckin",middleName:null,surname:"Ozkanlar",slug:"seckin-ozkanlar",fullName:"Seckin Ozkanlar"}]}],mostDownloadedChaptersLast30Days:[{id:"44699",title:"Apoptosis and Activation-Induced Cell Death",slug:"apoptosis-and-activation-induced-cell-death",totalDownloads:2949,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"2857",slug:"apoptosis",title:"Apoptosis",fullTitle:"Apoptosis"},signatures:"Joaquín H. Patarroyo S. and Marlene I. Vargas V",authors:[{id:"141183",title:"Prof.",name:"Joaquín",middleName:null,surname:"Patarroyo",slug:"joaquin-patarroyo",fullName:"Joaquín Patarroyo"},{id:"146188",title:"Prof.",name:"Marlene",middleName:null,surname:"Vargas",slug:"marlene-vargas",fullName:"Marlene Vargas"}]},{id:"44689",title:"Drug Resistance and Molecular Cancer Therapy: Apoptosis Versus Autophagy",slug:"drug-resistance-and-molecular-cancer-therapy-apoptosis-versus-autophagy",totalDownloads:4002,totalCrossrefCites:2,totalDimensionsCites:14,abstract:null,book:{id:"2857",slug:"apoptosis",title:"Apoptosis",fullTitle:"Apoptosis"},signatures:"Rebecca T. Marquez, Bryan W. Tsao, Nicholas F. Faust and Liang Xu",authors:[{id:"19713",title:"Dr.",name:"Liang",middleName:null,surname:"Xu",slug:"liang-xu",fullName:"Liang Xu"},{id:"149902",title:"Dr.",name:"Rebecca",middleName:null,surname:"Marquez",slug:"rebecca-marquez",fullName:"Rebecca Marquez"}]},{id:"51334",title:"Free Radicals and Biomarkers Related to the Diagnosis of Cardiorenal Syndrome",slug:"free-radicals-and-biomarkers-related-to-the-diagnosis-of-cardiorenal-syndrome",totalDownloads:3762,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The National Heart, Lung, and Blood Institute Working Group has postulated the cardiorenal syndrome (CRS) as an interaction between the kidneys and the cardiovascular system in which therapy to relieve congestive heart failure (HF) symptoms is limited by the further worsening renal function. CRS is classified from type I to V, taking into account the progression of the symptoms in terms of mechanisms, clinical conditions, and biomarkers. Experimental and clinical studies have shown the kidney as both a trigger and a target to sympathetic nervous system (SNS) overactivity. Renal damage and ischemia, activation of the renin angiotensin aldosterone system (RAAS), and dysfunction of nitric oxide (NO) system are associated with kidney adrenergic activation. Indeed, the imbalances of RAAS and/or SNS share an important common process in CRS: the activation and production of free radicals, especially reactive oxygen species (ROS). The present chapter addresses connections of the free radicals as potential biomarkers as the imbalances in the RAAS and the SNS are developed. Understanding the involvement of free radicals in CRS may bring knowledge to design studies in order to develop accurate pharmacological interventions.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"Carolina B.A. Restini, Bruna F.M. Pereira and Tufik M. Geleilete",authors:[{id:"178144",title:"Dr.",name:"Carolina",middleName:null,surname:"Baraldi A. Restini",slug:"carolina-baraldi-a.-restini",fullName:"Carolina Baraldi A. Restini"},{id:"178387",title:"Ms.",name:"Bruna",middleName:null,surname:"Pereira",slug:"bruna-pereira",fullName:"Bruna Pereira"},{id:"184159",title:"Dr.",name:"Tufik",middleName:null,surname:"Geleilete",slug:"tufik-geleilete",fullName:"Tufik Geleilete"}]},{id:"52345",title:"Oxidative Stress in Invertebrate Systems",slug:"oxidative-stress-in-invertebrate-systems",totalDownloads:2474,totalCrossrefCites:8,totalDimensionsCites:23,abstract:"Invertebrates have been valuable research models in the discovery of many scientific principles owing to the numerous advantages they provide. Throughout the life cycle, many of them thrive in pathogen-rich environments, manage harsh weathers, exposed to a number of allochemicals, and adapt well to both terrestrial and marine ecosystems. Their remarkable ability to cope up with the enormous oxidative stress generated in all these circumstances, make them attractive models in this field of research. Endocrine control of oxidative stress in insects is recently emerging. Adipokinetic hormone, glucagon, ecdysteroids and juvenile hormone have been implicated in antioxidative protective role in insects. Drosophila and Caenorhabditis elegans have provided the largest body of evidence addressing the free radical theory of ageing. Oxidative stress is also induced by pesticides/insecticides. In mollusks, pesticides exert their biological effects via generation of ROS. Oxidative stress has been shown to be associated with exposure to several organophosphorous compounds and different classes of pyrethroids. Malathion is a potential hazard to the environment. Adverse effects induced by malathion in earthworms and insects have been reported. Information is now available in great detail on the role of ROS in modulating insect immunity during parasite invasion and bacterial infection. In Drosophila melanogaster ROS are actively produced in the midgut at a basal level in the presence of commensal microbiota and highly generated upon bacterial challenge. The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. The concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens. Elevated oxidative stress was previously reported for a mosquito line experimentally infected with Wolbachia, indicating that oxidative stress may be important for Wolbachia-mediated antiviral protection. In a nutshell, this chapter highlights the current advances of oxidative stress in invertebrate model systems and its implications.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"R.K. Chaitanya, K. Shashank and P. Sridevi",authors:[{id:"178087",title:"Dr.",name:"Rk",middleName:null,surname:"Chaitanya",slug:"rk-chaitanya",fullName:"Rk Chaitanya"}]},{id:"51782",title:"Is Extracellular Matrix a Castle Against to Invasion of Cancer Cells?",slug:"is-extracellular-matrix-a-castle-against-to-invasion-of-cancer-cells-",totalDownloads:2333,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Metastasis is a complicated course that involves the spread of a neoplasm to distant parts of the body from its original site. A cancer cell must complete a series of steps before it becomes a clinically detectable lesion for successful colonization in the body. These are separation from the primary tumor, invasion and penetration of their basement membranes, entry into the blood vessels and survival within blood, and entry into lymphatics. A major challenge in extracellular matrix (ECM) biology is to understand the roles of the ECM and how disruption of ECM dynamics may contribute to cancer. A noteworthy area of forthcoming cancer research will be to determine whether abnormal ECM could be an effective cancer therapeutic target. We should understand how ECM composition and organization are normally maintained and how they may be deregulated in cancer. So the aims of this chapter were to focus on extracellular matrix. 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He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"28",type:"subseries",title:"Animal Reproductive Biology and Technology",keywords:"Animal Reproduction, Artificial Insemination, Embryos, Cryopreservation, Conservation, Breeding, Epigenetics",scope:"The advances of knowledge on animal reproductive biology and technologies revolutionized livestock production. Artificial insemination, for example, was the first technology applied on a large scale, initially in dairy cattle and afterward applied to other species. Nowadays, embryo production and transfer are used commercially along with other technologies to modulate epigenetic regulation. Gene editing is also emerging as an innovative tool. This topic will discuss the potential use of these techniques, novel strategies, and lines of research in progress in the fields mentioned above.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. 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Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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