Database linked to precision medicine in general and their links [30].
\r\n\t
\r\n\tThis book will intend to provide the reader all the necessary information on apheresis with a comprehensive overview including techniques for therapeutic apheresis, indications of apheresis in the light of guidelines, adverse events associated with apheresis, as well as the care of the apheresis patient.
Diabetes Mellitus is a chronic non-communicable epidemic that has become the most important in the world. Diabetic foot (DF) is one of the most common complications of diabetes. The global prevalence of diabetic foot is 6.3%, male are higher than female, and type 2 diabetes is higher than type 1 diabetes. The prevalence of diabetic foot varies greatly from country to country, varying from 1.5 to 16.6% [1]. DF is one of the primary causes of disability and death of diabetic patients, and it is also a major public health problem that causes a heavy burden on society.
It is estimated that there is one amputation of diabetic patients every 20 seconds in the world [2]. According to the statistics of the World Health Organization, about 50% of all non-traumatic amputations are due to diabetic foot amputation [3]. The annual mortality rate of patients with diabetic foot is as high as 11%, and the mortality rate of amputated patients is as high as 22% [4]; many studies have shown that diabetic foot costs are huge, accounting for about one-third of the entire diabetes medical cost. In 2017, the global medical cost of diabetes was as high as 727 billion US dollars, of which China was 110 billion US dollars [5]. In developed countries, diabetic foot occupies 12–15% of diabetes medical and health resources, while in developing countries, up to 40% [6]. One third of the medical cost of diabetes in the United States is used for diabetic foot patients [7].
Diabetic foot is the most common cause of hospitalization, with the characteristics of long hospital time, difficult treatment and high medical cost. According to recent big data from the United States, compared with ambulatory diabetic outpatients, diabetic foot patients are 3.4 times more hospitalized or emergency patients, 2.1 times more referrals to specialists, and 1.9 times more annual visits. Physicians spend more time on diagnosis and treatment; patients with diabetic foot infection (DFI) are directly referred to the emergency department or hospitalized by 6.7 times.
Diabetic foot is one of the main causes of disability and death of diabetic patients, and it is also a major public health problem that causes a heavy burden on society.
Diabetic foot involves a variety of factors including peripheral nerve tissue lesions, ischemic lesions, and reduced body immunity. It can be seen that the diagnosis and treatment of diabetic foot need to involve multiple disciplines and fields. With the development of medical standards, clinical knowledge and treatment of diabetic foot are constantly improving. Early diagnosis and intervention is the key to reducing the incidence of diabetic foot and improving the cure rate.
The causes of diabetic foot are multifactorial. Diabetic peripheral vascular disease, peripheral neuropathy and infection are the basic causes of diabetic foot, which can exist alone or in combination with other factors.
Diabetic foot is the destruction of the skin and deep tissues of the ankle joint of diabetic patients. It is often complicated by infection and/or arterial occlusive disease of different degrees in the lower extremities. In severe cases, muscle and bone tissues are involved. The World Health Organization has a clear definition of diabetic foot, foot infection, ulcers and deep tissue damage caused by abnormal nerves in the lower extremities and varying degrees of lesions in the surrounding blood vessels.
The following people are prone to diabetic foot: old, living alone, male, with a diabetes course of more than 10 years, a history of paraplegia, uncontrolled high blood sugar, and little knowledge about diabetes, combined with foot mold, deformity, calluses, etc.
For a DF patient, a comprehensive systemic condition assessment and a foot assessment are necessary. The foot assessment includes the blood supply of the foot, the size and depth of the ulcer, the condition and severity of ulcer infection. Diabetic foot ulcer classification assessment: cause classification, nature classification, then grading and staging, and finally select the appropriate treatment method according to grading and staging.
At present, the common clinical grading methods of diabetic feet include Wagner Ulcer Classification and University of Texas Diabetic Wound Classification. Wagner Ulcer Classification method is currently the most classic grading method. It is divided into 6 levels according to the depth of skin damage and the presence or absence of gangrene. The advantage of this grading system is that it is easy to use in clinical applications. It can be graded without auxiliary examination tools, and can also reflect the severity of ulcers and gangrene. The disadvantage of this system is that it does not reflect the etiology of the foot and lacks reproducibility and specificity when grading ulcers. In addition, superficial cases with or without ischemia cannot be correctly graded, and ischemia is only mentioned in grades 4 and 5.
Grade 0, No ulcers in a high-risk foot.
Grade 1: Superficial Diabetic Ulcer.
Grade 2: Ulcer extension Involves ligament, tendon, joint capsule or fascia.
No abscess or Osteomyelitis.
Grade 3: Deep ulcer with abscess or Osteomyelitis.
Grade 4: Gangrene to portion of forefoot.
Grade 5: Extensive gangrene of foot [8].
Stages.
Stage A: No infection or ischemia.
Stage B: Infection present.
Stage C: Ischemia present.
Stage D: Infection and ischemia present.
Grading.
Grade 0: Epithelialized wound.
Grade 1: Superficial wound.
Grade 2: Wound penetrates to tendon or capsule.
Grade 3: Wound penetrates to bone or joint [9].
Peripheral neuropathy is one of the important causes of diabetic foot. Relevant research data shows that patients with diabetes over 25 years have a 50% chance of developing peripheral neuropathy, and diabetic foot patients have the highest proportion of with neuropathy [10]. Studies have confirmed that the occurrence of neuroarthropathy is related to autonomic neuropathy; motor neuropathy can lead to metatarsal deformation in diabetic patients, foot muscle atrophy, and increased plantar pressure. In addition, neuropathy can cause diabetic patients to lose their ability to feel external stimuli and injuries, which is also a high-risk factor in the formation of skin injuries such as burns and abrasions.
Vascular disease is another important cause of diabetic foot. Long-term hyperglycemia in diabetic patients can cause lesions such as vascular intima damage and vascular occlusion. When the vascular lesions of the lower extremities occur in diabetic patients, they can lead to ischemia and hypoxia in the lower extremities, especially the feet, so that when they urgently need to increase blood circulation, the blood flow cannot increase accordingly, ulcers or even gangrene will occur. In addition, microcirculation disorders caused by vascular lesions can also lead to neuron dystrophy and aggravate nerve function damage, thereby increasing the incidence of ulcers.
Leukocyte dysfunction caused by dysglycemia in diabetic patients can lead to decreased immunity of the patient and prone to infection. Infection is also an important inducer of diabetic foot gangrene, and severe cases may even cause sepsis and be life-threatening. Studies have shown that Gram-positive cocci such as Staphylococcus aureus and Enterococcus faecalis are the main infections of mild infections, and Gram-negative bacillus infections of Proteus and Escherichia coli are the main infections of moderate and severe infections.
Foot deformity, smoking, obesity, visual impairment, alcoholism, and lack of knowledge about diabetic foot are all closely related to the occurrence of diabetic foot.
Comprehensive medical treatment is the basis of diabetic foot treatment, including strict control of blood sugar and blood pressure, lipid regulation, anti-infection, improvement of microcirculation, correction of hypoproteinemia, elimination of edema and various adverse factors affecting prognosis, etc.
The basic treatments of diabetic foot mainly include blood sugar control, improve systemic nutrition, strengthen anti-infective treatment, control blood pressure, blood lipids, improve local circulation and blood oxygen.
Diabetes patients due to long-term high blood sugar, glucose and nucleic acid and other macromolecular substances combine to cause damage or abnormal function of vascular endothelial cells, and then the blood vessel coagulation function is disordered, causing thrombosis and microcirculation disorders, and ultimately leading to extremities, especially feet ischemia, hypoxia, metabolic disorders, and even ulcer necrosis [11].
Several studies have confirmed that good blood sugar control can effectively reduce the incidence of microvascular disease. Intensive blood glucose management with the A1C goal of <7% is associated with a reduction of microvascular and neuropathic complications of diabetes, and also can lead to a 25% risk reduction of amputation compared to less intensive glycemic management [12]. One systematic review of 19,234 patients also concluded that enhanced blood glucose control can significantly reduce the risk of amputation in patients with DF.
Hypertension is the main risk factor for lower extremity arterial disease. For diabetic patients with hypertension, early control of blood pressure can significantly reduce the occurrence of macrovascular disease. Angiotensin converting enzyme inhibitors are recommended, but other antihypertensive drugs can also be used. Diabetes patients with lower extremity arterial disease are often accompanied by dyslipidemia [13]. On the basis of diet control and exercise lipid-lowering, combined with statin lipid-lowering treatment can help the healing of foot ulcers [14].
Diabetic foot infection (DFI) is one of the most important causes of patients’ deterioration, amputation and death. However, after proper treatment, most patients can be cured. Therefore, active treatment of DFI is beneficial to patients, society, and economy. Multi-drug resistant bacterial infections often indicate a poor prognosis [15].
Once DFI is established, the severity of DFI must be graded. The classification tool recommends the IWGDF/IDSA infection grading system. Antibiotic treatment of diabetic foot infections cannot replace thorough wound debridement treatment. Thorough and adequate debridement and drainage is the basis of effective anti-infective treatment [16].
Treatment principles: thorough and effective debridement is directly related to wound healing. For different types of wounds, the timing debridement should be accurately grasped; physical debridement is the basis of wound treatment. When physical debridement is not suitable, autolytic debridement, Enzymatic debridement, traditional dressing debridement and maggot debridement and other types of debridement should be considered. Decompression treatment of diabetic foot ulcers should adhere to the principle of individualization and continuity, combined with the condition of infection and lower limb ischemia, patients’ wishes and ulcers types.
A prospective study of diabetic foot ulcer patients with co-infection showed that in the first year after infection, 15.1% of patients died and 17.4% of patients had at least part of their lower limbs amputated [17]. Studies have found that 49% of diabetic foot ulcer infections are mixed infections. The main pathogens are Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae [18]. In addition to timely and reasonable surgical treatment of wounds, it is necessary to select antibiotics against common pathogens and early anti-infective treatment according to experience before obtaining the results of pathogenic examinations, and adjust sensitive antibiotics according to the results of pathogenic examinations. In order to improve the positive rate of culture, it is recommended to carry out pathogenic culture or histological examination of deep tissue scrapes before antibiotic treatment, and avoids the use of swab specimens [19]. The use of antibiotics is not recommended for ulcers without signs of infection, the initial antibiotic treatment plan for foot ulcers with infection is an empirical choice, but requires the cultivation of ulcer tissue microorganisms before the application of antibiotics. If clinical treatment is effective, although microbial culture plus drug sensitivity tests show insensitivity, the original treatment plan is suggested. If the patient is not effective with the empirical plan or the infection progresses, antibiotics need to be replaced according to the culture results; mild infection (skin or subcutaneous tissue) takes 1–2 weeks of treatment; moderate to severe infection 2–3 weeks.
For patients with diabetic foot combined with osteomyelitis, the diagnostic methods include clinical examination, such as probe and bone test (probe to bone test): the method has a sensitivity of 66%, a specificity of 85%, and a positive predictive value 89%. X-ray radiograph is little significance for the diagnosis of osteomyelitis, and repeated radiographs every 2–4 weeks can find bone destruction and increase the detection rate of osteomyelitis, MRI is more sensitive to the diagnosis of osteomyelitis 95%, but less sensitive to osteomyelitis with smaller bones. Bone scan and CT are of little significance for the diagnosis of osteomyelitis, bone biopsy is the gold standard for diagnosis, and histological culture results can guide antibiotic selection.
Treatment methods include: anti-infection alone, anti-infection combined with minor surgery: drainage of pus, removal of infected bone, etc.; amputation (toe) combined with antibiotic treatment. Compared with surgical treatment, antibiotics alone are cheaper to treat osteomyelitis, but about 17% are ineffective. Gram-positive cocci infections are the most common bacteria. Broad-spectrum antibiotics are usually selected, and the course of treatment is 6 weeks to 6 months.
Local treatment of the wound surface is essential for the healing of diabetic foot ulcers. If treated properly, it can accelerate the healing of ulcers. The “wet healing theory” and “wound bed preparation theory” are innovative developments in chronic wound specialty care in recent years. Wet healing has the following advantages: regulating the oxygen tension of the wound surface and promoting the formation of capillaries, retaining the content contained in the wound exudate tissue proteolytic enzyme is conducive to the dissolution of necrotic tissue and fibrin, promotes the release of various growth factors, maintains the constant temperature of the wound, facilitates the growth of the tissue, without the formation of scabs, and avoids the mechanical damage of the new granulation tissue, protects the nerve endings of the wound, and reduce pain. The core content of “wound bed preparation” is that the wound surface can be divided into four stages of black, yellow, red, and pink according to the color of the wound base. The black stage and the yellow stage are suggested to use of debridement and the use of antibacterial dressings to remove necrosis, and bacterial load. In the red period, treatment with growth factors such as basic fibroblast growth factor, hydrogel dressing, alginate dressing, etc. can promote the proliferation of granulation tissue of the wound surface and quickly fill the wound defect. The powder phase is mainly to protect the wound surface and promote epithelialization, and perform skin grafting when necessary.
In terms of debridement technology, in addition to traditional surgical debridement, some new debridement techniques have emerged. Such as autolytic debridement, chemical (protein solubilizing enzyme) debridement, mechanical debridement (including ultrasonic debridement waterjet and wound negative pressure treatment, etc.) and biological (maggot) debridement, etc.. These techniques have their own advantages and disadvantages, so clinicians should master their adaptations and contraindications, choose the most appropriate debridement method for different ulcer conditions, and ensure the maximum therapeutic effect. In addition, the above method is only applicable to neurological ulcers or neurovascular ischemic ulcers. For ischemic ulcers, if the affected limb ischemia is severe, excessive local debridement should be avoided. Vasodilator drugs, intraluminal balloon dilation, stent placement, or vascular bypass surgery and autologous stem cell transplantation can be used to improve limb blood supply. When the blood supply of the affected limb improves, local debridement treatment can be performed to remove excessive keratosis, infected and inactivated tissues.
The application of dressings can help promote the healing of ulcers, and the “wound bed preparation theory” can guide the choice of dressings. It is clinically recommended to use hydrogel dressing in the black period to fully soften dry necrotic tissue; the yellow period mainly removes bacterial load, absorbs excessive wound exudate, promotes the growth of granulation, transitions to the red period, alginate dressing, hydraulic adhesive dressings and antimicrobial dressings are suitable choices. The red stage and powder stage are the period of granulation and epithelial growth, and the leakage is reduced, ultra-thin hydrocolloid dressings or biological dressings containing growth factors can be choose.
The wound repair process involves the role of many cytokines, including epidermal growth factor, vascular endothelial growth factor, transforming growth factor -β, fibroblast growth factor and erythropoietin, etc. These cytokines have a promoting effect on the proliferation of fibroblasts and capillaries, the migration, granulation tissue growth and wound epithelialization, which ultimately promotes wound healing in diabetic patients [20]. In terms of promoting the growth of ulcer granulation, there are currently a variety of synthetic growth factors such as platelet-derived growth factor, basic fibroblast growth factor, human epidermal growth factor and transforming growth factor [21, 22]. In addition, APG shows a more obvious advantage in the treatment of refractory skin ulcer sinus tract closure. Survival analysis of sinus tract closure time suggests that the closure rate of APG treatment on the sinus tract is significantly better than standard treatment, suggesting that APG is used to treat refractory diabetic skin. Effective, safe and feasible in ulcers.
For those with severe ischemia and poor medical treatment, surgical methods should be used. The ultimate goal is to reduce the pain caused by ischemia, promote ulcer healing, avoid amputation due to limb necrosis, and improve the quality of life. The surgical treatment of diabetic foot mainly includes percutaneous endovascular interventional therapy, surgical vascular bypass reconstruction, stem cell transplantation and amputation.
For patients who are ineffective for medical treatment and are not suitable for minimally invasive treatment of the vascular cavity, surgical vascular reconstruction surgery is recommended. Surgical treatment includes arterial endarterectomy, artificial blood vessel and/or autovascular bypass. Surgical treatment requires that the patient can tolerate anesthesia and surgical shock.
Percutaneous endovascular interventional treatment includes traditional percutaneous balloon dilatation (PTA), stent implantation, percutaneous intimal circumcision, and Pedal-Plantar Loop technology for small vessel disease of the foot. In recent years, with the invention of new types of balloons and stents (drug-coated balloons and stents, etc.), especially the application of a series of products with small diameters and long balloons dedicated to lower extremity arteries, the long-segment occlusion lesions and infra-knee arteries significantly improved clinical efficacy. For diabetic inferior knee arterial disease, the technical success rate of PTA alone is 86%, the 1-year patency rate is 53–56%, and the limb salvage rate is 81–85%. The 1-year patency rate is 54%, and the limb salvage rate is 97.1%, but there is a risk of contrast-related nephropathy, especially in patients with potential or renal insufficiency, the incidence is higher and the prognosis is poor. Therefore, for patients with ischemic ulcers, when clinically considering the use of percutaneous intravascular interventional therapy, adequate hydration should be performed and the changes in renal function of the patients should be closely monitored.
If autologous vascular bypass is performed, a good saphenous vein is also required. By-pass surgery using autologous blood vessels, the 5-year patency rate was 63%, and the salvage rate was 78%. For the treatment of sub-knee occlusion with saphenous vein bypass, the patency rates at 1 and 3 years were 63 and 50%, and the salvage rates were 85 and 79%. When the foot disease further develops and leads to irreversible ischemic necrosis of the limb, or necrosis of the affected limb with serious infection that cannot be controlled, directly threatens the patient’s life, or the long-term spasm of the distal small artery due to severe peripheral neuritis causes the limb to become distant. For patients with end-stage ischemic necrosis, amputation is not only a treatment method, but more importantly, it can save the patient’s life. For diabetic foot amputation, the amputation plane should be reduced as much as possible on the premise of ensuring the amputation effect, and arteriography should be performed before the amputation to determine the amputation plane.
The systematic review shows that multidisciplinary team collaboration therapy can focus on the advantages of various professions, which has a positive impact on shortening wound healing time, reducing amputation rate and reducing the severity of amputation [23]. The treatment of diabetic foot requires clinical multi-disciplinary collaboration. The diabetic specialist first evaluates the patient’s systemic condition to minimize the occurrence of cardiovascular complications; at the same time evaluates vascular conditions and creates percutaneous vascular intraluminal intervention treatment or surgical treatment conditions, discuss operative methods with vascular surgery and endovascular interventional physicians, orthopedic physicians, make rescue plans for intraoperative and postoperative cardiovascular events, and follow-up and drug adjustment after successful surgery. Only in this way can the blood circulation reconstruction of diabetic foot patients be improved to the greatest extent, and amputation and death rates can be reduced. Early and timely multi-disciplinary collaborative treatment is also recommended by the domestic 2017 version of the guidelines.
A multi-disciplinary team of diabetic foot medical care professionals can effectively reduce the rate of diabetic amputation and medical expenses, and improve the quality of life of patients. In the recently reported 240,000 rural areas of England, after the establishment of a multidisciplinary team of diabetic foot led by vascular surgery experts, the amputation rate of diabetic lower limbs decreased from 412 per 100,000 to 15–44 per 100,000 [24]. The changes in medical services are reflected in: increasing the community’s awareness and clinical path to this multidisciplinary collaborative podiatry team service, as far as possible, patients are admitted to specialty wards, a rapid referral channel, an operation room in the outpatient department for debridement, small amputation; a podiatrist, orthopedics and vascular surgery joint outpatient clinic; the hospital’s senior podiatrist and community podiatrist have a network of links to pay attention to diabetic patients. For patients who need to strengthen outpatient follow-up, implement weekly or 2 weeks, a joint outpatient clinic; hospital specialists and nurses follow up the patients closely to achieve clinical follow-up at the patients’ homes. The French medical management department requires that patients with diabetic foot must be referred to a hospital with a diabetic foot care team within 48 hours.
Despite the rapid development of endovascular interventional techniques and surgical techniques, there are still some patients with ischemic foot disease can’t receive interventional or surgical treatment. This part of patients is called “no Treatment Options for Patients. Recent clinical trials on autologous stem cell transplantation for lower limb ischemia have achieved satisfactory results. Tateishi-Yuyama et al. [25]. reported for the first time that bone marrow stem cell transplantation was used to treat patients with peripheral vascular disease, local autologous bone marrow mesenchymal stem cells were sprayed locally on chronic ulcers with a duration of more than 1 year. The wounds began to close after 2–4 weeks, and the wound healing rate was proportional to the number of stem cells; a 3-year follow-up of patients with autologous bone marrow mononuclear stem cell transplantation for the treatment of arterial ischemic diseases of the lower extremities showed that this treatment can improve the ischemia of the lower extremities for a long time and prolong the survival time of the affected limbs. Lu et al. also confirmed that bone marrow mononuclear stem cells and bone marrow mesenchymal stem cells can promote ulcer healing, prolong the claudication distance, increase ankle brachial index and percutaneous oxygen partial pressure in patients with diabetic foot, however, the effect of latter is better than the former. In addition, the combined application of stem cell transplantation and interventional therapy can make up for their respective shortcomings, and benefit more than a single method. Therefore, for patients with “no treatment options”, consider referral to a qualified medical unit for autologous stem cell transplantation treatment. Although this treatment method is still under exploration and research, it is still its hope for future treatment.
Peripheral neuropathy, lower extremity arterial disease (LEAD), and foot deformities are the main reasons for the increased risk of DFU. Age, gender, education, economic conditions, lifestyle habits and other complications or complications of diabetes are also important factors. Fully understanding these factors is very important for the risk assessment of diabetic foot and taking corresponding preventive measures.
The patient’s quality of life is low, mental and psychological pressure is high, and the medical cost burden is heavy. Therefore, early evaluation to prevent foot ulcers and timely cure of ulcers to prevent recurrence, thereby avoiding amputations or large amputations above the ankle joint, is the focus of DF tertiary prevention.
It is generally believed that the preventive measures against DF should be divided into three levels. Primary prevention is to identify and avoid the risk factors that lead to DF as early as possible to prevent its occurrence; secondary prevention is to identify DF as early as possible and prevent its progress; tertiary prevention is to ensure appropriate treatment of DF.
The main risk factors for DF include diabetic peripheral neuropathy, foot deformity, peripheral vascular disease, foot ulcer history, foot amputation or leg amputation history. According to the recommendations of the International Diabetes Foot Working Group (IWGDF), for patients with diabetes without high-risk factors, a foot examination should be performed by a specialist at least once a year. For patients with high-risk factors, more frequent inspections should be conducted according to the category of high-risk factors, in order to detect these high-risk factors and their progress as soon as possible, and provide patients with appropriate measures to prevent foot ulcers [26].
Systematic diabetic foot related knowledge education can reduce the incidence of DFU, reduce the recurrence rate of DFU and improve the survival rate of footless ulcer events, reduce the amputation rate of DFU, reduce medical expenses and improve the quality of life of patients [27, 28]. Diabetic foot specialist medical staff educates patients and their families on foot protection knowledge and nursing, and helps them transform into effective actions [29]. Although there are few clinical studies that specifically assess whether health education can prevent DFU, and the level of evidence is low [30], these health education measures can enable patients to detect early lesions of DFU, strengthen self-behavior management, and keep feet clean which are important means to prevent ulcer occurrence and recurrence [31].
Predictors of DF amputation or re-amputation include adult males, long-term diabetes, wound infections, diabetic neuropathy, and smoking history [32]. DF occurs mostly in manual workers, patients are generally less educated, lack knowledge of diabetes prevention, lack of awareness of the severity of its complications, and pay insufficient attention to early blood glucose control and DF prevention. Therefore, we must pay attention to the health education of diabetic patients, so that they have a full understanding of the development and outcome of the disease, so as to actively cooperate with prevention, such as actively quitting smoking, controlling blood sugar, doing daily foot inspections, and doing foot protection., Foot care, pay attention to toenail trimming and comfortable footwear, etc., in order to detect and avoid the risk factors of DF as early as possible, to prevent the formation of ulcers, infections and further development.
Qualified DF protective shoes can significantly reduce the incidence of foot ulcers. The custom-made DF protective shoes generally have the following functions: protect the sense of loss from external damage; adapt to the deformity of the foot to reduce pain and prevent the increase of the deformity of the foot; reduce excessive local pressure, so that the pressure is evenly distributed; reduce shear force in vertical and horizontal direction [33]. Multiple studies have shown that wearing foot protection shoes can effectively reduce plantar pressure by about 30%. Compared with wearing ordinary shoes, the risk of foot ulcer recurrence in DF patients is reduced by 46.1–70.2%. For patients with high-risk feet with hammer-toe diabetes who are not ideal for the use of conservative measures such as protective shoes, distal flexor tendon amputation can prevent the formation of tip toe ulcers, and its cost performance and risk-benefit ratio are encouraging [34].
For diabetic patients with risk factors for podiatry, early completion of diabetes peripheral neuropathy (DPN), vascular disease and podiatry screening, early detection and management of these high-risk patients are needed. Non-diabetic foot medical staff should refer to the diabetic foot specialist or consult with the specialist in a timely manner for patients with the following conditions: sharp changes in skin color, increased local pain and inflammation such as redness, new ulcers, original There are superficial ulcers that deteriorate and involve soft tissue and/or bone tissue, disseminated cellulitis, signs of systemic infection, osteomyelitis, etc. Timely referral or consultation can help reduce the amputation rate and reduce medical costs, and timely intervention of the surgeon can help reduce the diabetic amputation rate and amputation plane.
Therefore, it is currently emphasized that for patients with diabetes, screening of lower extremity arterial diseases should be strengthened to achieve early diagnosis and early treatment. For patients with moderate to severe lower extremity arterial disease and complete foot skin, it is recommended to guide the patient to exercise rehabilitation exercise for at least 3–6 months, but for patients with foot skin ulcers, it is recommended to brake and avoid exercise rehabilitation At the same time, it is recommended to use low-dose aspirin, statin lipid-lowering drugs, angiotensin-converting enzyme inhibitors, vasodilator drugs and anticoagulant drugs, which can reduce the occurrence of ulcers and improve patients’ lower limb motor function.
This work was financially supported by “Graduate education innovation program project of Guangdong province” (No. 2020XLLT10) and “Twenty-one teaching reform projects of Jinan University” (No. JG2019044). The funding body supported the team to design the study and collection, analysis, and interpretation of data and write the manuscript.
The authors declare no conflict of interest.
The functional responsibility of the immune system (humoral and cell-mediated alike) is to protect against infection by destroying various infectious agents when such agents attack the body or are introduced through vaccination [1]. The functioning of the immune system is coordinated and maintained by a sequence of highly regulated and physiological mechanisms which aids the identification and recognition of both body cells and foreign cells [2].
The body’s immune units usually coexist with other cells of the body that carries a self-marker molecule. Immune reactions are only triggered when an antigen which could be a microbe, part of a microbe or a molecule is presented to the surface of the cell and perceived by the body defenses [3].
The immune system of humans is made up of two divisions which are innate and acquired immunity. The innate immunity forms the first line of defense immediately after infectious agents are recognized by the body while acquired immunity functions in the removal of pathogens at the later phase of infection [3].
When the immune system is stimulated, it targets and destroys foreign units. Still, in some abnormal situation, the immune system might be insensitive to antigens, hypersensitive to antigens or recognize the cells with self-marker as foreign cells [2].
There are disease conditions that affect the immune system, which leads to different degree and types of conditions known as the Immune diseases. Diseases of the immune system include inherited and acquired immunodeficiency and immune-proliferative disorders which includes malignancies of the immune system (multiple myeloma, lymphoma, and leukemia), autoimmune diseases (rheumatoid arthritis), and immune hypersensitivities (allergies) [4]. Inherited immunodeficiency, also is known as primary immunodeficiency, refers to a large number of immune disorders which alters either or both development and function of the immune system. Primary immunodeficiency implies conditions resulting from loss of function, a gain of function or loss of expression due to monogenic germline mutations [5]. External and environmental factors can induce an adverse effect on the immune system, and this is regarded as secondary or acquired immunodeficiency, which is encountered commonly in clinical practice and could arise from quite a number of conditions [6].
The evolvement of medical practices especially diagnosis and treatment from the usual “one size fits all” approach to a more genetic and detailed patient stratification in a bit to acquire more information about the disease condition and the patient is known as personalized medicine [7].
The complexity of the body defense system and the ability of the cells associated with it to shift between different activation states under physiological and pathological conditions are some of the reasons for diversity in the treatment approach. The immune diseases at times are diverse, and this result in variations in response to therapy. The difference in the disease course also create reasons why there should be the identification of personalized marker for diagnosis of immune disease. Therefore, the use of genetic assessment to determine the best possible therapeutic approach from the numerous available options with different mechanisms, risks, and efficacy are essential [7, 8].
The Precision medicine data types, genomic data in precision medicine, genomic and personalized medicine databases, data sharing, access and use are discussed in this chapter. Also, the use of genomic methods and data in the understanding, diagnosis of diseases using specific biomarkers, monitoring of prognosis using prognosis biomarkers, personalized treatment of immune disorders, monitoring of response to treatment using response biomarkers are also described in this chapter.
Immunity is the ability of the body to prevent infection by resisting the invasion of such a body by harmful microorganism knows as infectious agents. Immunity can be categorized broadly into two types which are:
Innate or Natural Immunity and
Acquired Immunity
The initial host protection against diseases- causing agents is the innate immunity which is mediated by phagocytes. Through germline-encoded pattern-recognition receptors (PRRs), the innate immunity of the human body recognizes microorganisms invading its body. For the immune cells to be activated, different classes of the PRRs, which include Toll-like receptors and cytoplasm receptors recognize distinct and important microbial component of invading microorganisms thereby activating immune cells [3, 9].
Immediately after the detection of non-self-agents by PRRs which could be exhibited on the outer membrane of the cell, in intracellular parts, or released in the bloodstream and fluids of the body tissues, the PRRs then perform the function of opsonization, stimulation of complement and coagulation outflow, phagocytosis, initiation of pro-inflammatory signaling pathways, and inception of apoptosis. These cascades of intracellular signaling induce the expression of overlapping and unique genes which are involved in the inflammatory immune responses and essential in precision medicine. The reaction by the innate immune system is carried out by phagocytes (neutrophils, monocytes, and macrophages), inflammatory mediators releasing cells (basophils, mast cells, and eosinophils), and natural killer (NK) cells [3, 10].
Acquired immunity is the immunity that is developed against an infectious agent by the body after the previous encounter with a pathogen or a type of immunity developed by a child by the exchange of protective materials from mother to child before and after birth or by the injection of such substances. The mediation of adaptive immunity is the function of clonally distributed T and B Lymphocytes whose characteristics are the possession of specificity and memory. Many at times, activation of the innate immune response can trigger acquired immunity. The generation of Helper T cells subsets and the production of cytokines influence adaptive immunity [11, 12].
When naïve T-helpers cells are stimulated by Antigen-presenting Cells otherwise known as APCs, they differentiate into two subsets of T helper (TH) cells such as TH1 and TH2. Interferon-γ (IFN-γ) is produced by TH1 cells that solely promote cellular immunity. TH2 cells, on the other hand, produce interleukin 4, 5, 10 and 13 (IL-4, IL-5, IL-10, and IL-13). Whereas, IL-12 is the propelling source of TH1 separation while IL-4 stimulates TH2 distinction. TH2 is majorly involved in the promotion of humoral immunity [12].
The occurrence of the immunological disease is consequent to the dysregulation of numerous and different part of the human immune system. Fundamentally, the response of the immune system recognizes and eliminates antigens but tolerates its tissues. However, predominant immunopathology lesion is the basis on which the characterization of immune-mediated diseases is based. Immune-mediated disorders can be grouped into immediate hypersensitivity, autoimmunity, immune-complex disease, and delayed-type hypersensitivity. Autoimmunity can be further classified into those mediated by adaptive immunity and those mediated by innate immunity. Most of the disorders lie between the two, which will be best described as positive pathological feedback between innate and adaptive immune mechanisms [13]. Figure 1 below represents the pathogenesis of immune diseases.
Schematic representation of the pathogenesis of immune diseases.
Personalized medicine is the process of tailoring the diagnostic procedures, treatment, and preventive measures towards the characteristics of individual patients to get an optimal outcome for each patient while emphasizing easy accessibility and cost-effectiveness [14]. In the practice of personalized medicine, the characteristics of an individual, including the uniqueness of its genetic profile guide the clinical decision in the treatment. Prognostic, diagnostic and predictive biomarkers are always being searched to guide these clinical decisions, at the same time, ensure that the best treatment is offered to the right patient at the best time [15]. The division of personalized medicine is illustrated in Figure 2.
Diagram showing the different division of precision medicine.
While the method of application of precision medicine is given in Figure 3.
A flow chart representing application method of precision medicine.
Generally, personalized medicine compose of a vast collection of genetic data. The development of power systems has helped to increase the effective use of big data in personalized or precisions medicine over time. Also, the evolution of genomics data offers limitless possibilities in the design of clinical procedures, diagnostic, prevention, addressing and prediction of most favorable therapeutics for many diseases that are related to different regions and lineage [16].
The systematic collection of patient information is now accumulating and gaining complexity, as seen in the case of neuroimaging, which is currently producing above ten petabytes of data every year [17]. Studies in the field of precision medicine research make use of relevant data types such as Imaging data (CT, PET, UltraSound and MRI), bio-sample data (serum, plasma and urine value), molecular data, genomics data (nucleotide sequences), proteomic profiling data (mass spectrometry), digital pathology data, biomedical instrument data (blood pressure, heart rate and insulin level) and clinical data (death/survival data, demographics and medical-based questionnaire) and others [18].
Some of the achievement in Precision medicine has led to solutions, such as the birth of personalized brain models for a patient with intractable epilepsy [19] and the success in epigenetics mechanism of hematopoiesis [20]. The combination and integration of these data types require a sound understanding of the different fields of informatics (data science, data management and data curation) and bioinformatics [18].
A database is an ordered set of structured information or data usually controlled by the database management system (DBMS) in an electronic computer. The data, DBMS and the applications associated with them are called database system or database in short. Each database contains certain types of data; here, we will be introducing some of the database associated with personalized or precision medicine.
The IEDB is a free to use database that is very useful in vaccine and drug development, this database catalogs data such as experimental data on antibodies, Major histocompatibility complex (MHC) binding data from different antigenic sources, Helper T lymphocyte (HTL) and Cytotoxic T Lymphocytes (CTL) epitopes for human and other animal species. This database also aids in prediction and analysis of varieties of epitopes [21]. This database can be accessed through
Lifestyle medicine is the study of association between lifestyle, chronic and immune diseases. PCaLiStDB is a lifestyle database that is channeled towards precision in the prevention of prostate cancer and other diseases associated with lifestyle. The data found in this database are lifestyle associated genes, lifestyle type biomarkers and personalized lifestyle-disease associated predictors [22]. The database link is
ClinGen database provides data that are of clinical importance, this database is funded by the National Institute of Health (NIH), and it is aimed at collecting necessary data for use in precision medicine and research. Data such as clinically relevant gene and variants are retrieved from this database in making precise diagnosis and treatment [23]. This database is accessed via
One of the breakthroughs of medical informatics is the personal genome project database. This is an open-access database that is channeled towards the development of a tool for personalized medicine and advancing research. The database provides a wide range of data for different regions (PGP-UK, PGP-AUSTRIA, PGP-CHINA, PGP-CANADA and PGP-UNITED STATE, etc.). Data such as Genome, Methylome, transcriptome and phenotype data are retrieved from this database for use in the procedure of precise medicine [24]. The database can be linked through
This database was initiated in the early 1960s, and the online version was created in 1985. OMIM is an open-access database that is mainly built for professionals concerned with genetic disorders, a genetics researcher and advance students in medicine. Data such as human gene, genetic disorders, clinical features, phenotype and genes are available [25, 26]. This database address is
This is a variant-related database that collates already known gene lesion that is responsible for human inherited diseases. The database includes precision medicine data such as gene symbol, genomics coordinates, splicing, different disease, phenotype and mutations in the human genome [27, 28]. This database is accessible via
Clinical Genomic Database fills the critical niche in the field of clinical and genomic medicine; it also encompasses medically significant genetic data with available interventions. For each entry in the database, the CGD gives out data such as allelic conditions, gene symbol, clinical categorization (both manifestation and interventions), affected age groups mode of inheritance and pathogenic mutation for all diseases so far captured [27]. This database can be accessed via
There are other ongoing database projects to improve the existing ones, an example of this is The Human Variome Project [29]. Also, there are many websites and databases linked to precision medicine that this chapter cannot introduce all. Table 1 below provides more of the database related to precision medicine in general and their links [30].
Database | Link |
---|---|
Pathway Interaction Database | |
VirusMINT (interaction between viral protein and human) | |
AutDB (animal model resources) | |
Pathogen Interaction Gateway ((host and pathogen interaction) | |
NetPath (signal transduction) | |
Entrez – (encompasses sub-Databases) | |
GeneCards | |
Human Genome Resources | |
Ensembl Human Genome Browser | |
Online Mendelian Inheritance in Man (OMIM) | |
GeneCards | |
Entrez Gene | |
National Institute of Neurological Disorders and Stroke (NINDS): Clinical and Translational Resources | |
Database of Genotypes and Phenotypes (dbGaP) | |
NIH Chemical Genomics Center | |
Gene Expression Omnibus | |
ENCODE Project: ENCyclopedia of DNA Elements, NHGRI | |
PubChem | |
PhenX Toolkit | |
Human Genome Project, NHGRI | |
NCBI BioSystems | |
National Human Genome Research Institute (NHGRI) | |
Kyoto Encyclopedia of Genes and Genomes | |
HUPO Brain Proteome Project | |
ExPASy Proteomics Server | |
HUPO: Human Proteome Organization | |
European Proteomics Association (EuPA) |
Database linked to precision medicine in general and their links [30].
Data sharing is the potential inherent in the exchange of the same data resource with many applications or users; it encompasses the transferring of copies, accessing and enabling the reuse of data. Data can be open access (publicly available) or controlled (restricted), also, sharing data encompasses both sharing of primary (in case of nucleotide sequences) and secondary data (already used or analyzed data) [31].
Figure 4 above illustrates that precision medicine data encompasses both hospital data (information), GIS and PGHD. Sharing of the Precision medicine information (clinical data) can be accessed openly or otherwise restricted, whereby authorization will be needed by an authorized person to access and use the specified data for therapeutic, diagnostic and research purpose.
Semantic diagram of genomic and personalized medicine data sharing (LIS: Laboratory Information System; GIS: Genome Information System; EHR: Electronic Health Record; PGHD: Person Generated Health Data; PACS: Picture Archives and Communication System; CPOE: Computerized Physician Order Entry).
Autoimmune diseases are disease conditions where the immune system respond to self-antigens as a result of damage or dysfunction or disorder in the tissues. It is controlled by a whole lot of factors of which host gene and environment play a vital role. It could affect the entire body, selected systems or selected organs and an interplay between genetic makeup with environmental factors and the self-antigen presented for recognition controls which organ or system of the body that will become the target of the immune system [32, 33].
The precision medicines of the following autoimmune diseases are discussed below:
Multiple Sclerosis
Myasthenia Gravis
Pernicious Anemia
Rheumatoid Arthritis
Sjogren Syndrome
Lupus Erythematosus
Type 1 Diabetes
Multiple sclerosis is an inflammatory/autoimmune disorder that selects the myelin in the central nervous system which is capable of affecting patients of all age and causing neurologic disability when not adequately managed [34, 35]. More than 200 loci have been identified as an independent contributor to the pathogenesis of multiple sclerosis [36]. Multiple sclerosis is usually diagnosed between age 30 and 50 in most patients and occurs more often in females than male. The best way to understand the pathogenesis of multiple sclerosis is to address it from a multifactorial perspective with a model that proposes the interaction among genetic, epigenetic, infectious, dietary, climatic, or other environmental effects, together with sunlight exposure, and smoking. These interacting factors leads to self-intolerance and depreciation of immune homeostasis in the central Nervous system [34]. The brain and spinal cord tissues get infiltrated by stimulating peripheral mononuclear cells, and this leads to the loss of myelin, gliosis, which often leads to neurological dysfunction. Two primary approach of treatment has been given to the patient with multiple sclerosis due to the autoimmune model of the pathogenesis of such disease [34]. The former treatment is the use of global immunosuppressive agents which are aggressive. At the same time, the latter is the use of more specific agents to target specific elements of the immune system.
The contribution of common variants to multiple sclerosis has been probed, and different HLA alleles variants have been modeled for their contribution to multiple sclerosis and were found to be almost as common in control as it is in the sample as it was observed that OR of the statistical analysis tends towards 1 with an increase in sample size [37]. Biomarkers are important in the genetic assessment of Multiple Sclerosis as they possess the ability to express diverse aspects of multiple sclerosis heterogeneity. They also help in the diagnosis, stratification, and disease course prediction, identification of beneficial therapies and development of a precise treatment based on the predicted treatment response. As of 2016, MRI has turned to the most appropriate tool in the diagnosis of MS. The recommendation for brain MRI is the use of 1.5 T field strength, but 3.0 T is deemed preferable. However, using 7 T field strength has been supported by recent evidence to detect central vein in brain lesion of MS patients, but this can also be depicted using T2-weighted sequences at 3 T which help in the differentiation from microangiopathic lesions. The use of MRI for the diagnosis of MS seems simplified but its complexity sets in the differentiation of MS from other disease conditions like neuromyelitis optical spectrum disorders (NMOSD) which also has short spinal cord lesion at the onset. T2-weighted and contrast-enhanced T1-weighted brain MRI are recommended for the monitoring of disease progression while MRI of the spinal cord is not encouraged. Other than the MRI biomarkers there exist a few body fluid biomarker which could mark different stages of MS disease and differentiate each step from other similar disease conditions [34].
Body fluid biomarkers can be divided into three main groups, including those marking the early phase of MS, those associated with disease course and those associated with treatment response. Low vitamin D level in Cerebrospinal fluid is a marker of the initial stage of MS. Astrocyte-derived chitinase 3-like 1 (CHI3L1) in the CSF is also a prognostic marker of which an increased level of CHI3L1 in the CSF is a significant independent risk factor connected with the progression of disability in multivariate Cox regression models. Utilizing a proteomic approach and verification of result with ELISA confirmed that CHI3L1 would be the best predictors of the conversion to MS in CIS patients. CSF CHI3L1 level with MRI and age were the best predictors of MS risk in a multivariable analysis. Neurofilaments (NF-L) has also been implicated as a biomarker in the early phase of MS [36, 37].
Transcriptional regulator high-mobility group box protein 1 help differentiates patients with relapse-onset MS from patients from primary progressive MS. Proteomic studies show that two isoforms of vitamin D-binding protein and apolipoprotein E permit discrimination between MS patients with aggressive and benign disease courses [36]. During the disease course, calcium-binding protein secretogranin-1 is decreased in the CSF when compared with the early phase of MS. Stable MS patients, when compared with relapsing patients, possess an increase in B cell activating factors in their plasma samples. Solute carrier family 9, subfamily A (SLC9A9) is a biomarker associated with the non-response to IFN beta. Upregulation of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome is also a biomarker for non-responsive IFN beta treatment. Biomarkers of glatiramer acetate response are feedback gene to complement 32 (RGC-32), FasL, and IL-21. Up-regulated mRNA expression levels of RGC-32 and FasL and reduced expression of IL-21 seen in peripheral blood cells from responders in contrast to non-responders forms the basis for the use of these biomarkers [34, 36, 37].
Myasthenia gravis (MG) is an autoimmune disease treated with chronic immunosuppression due to the actions of autoantibodies against the diverse structure of the neuromuscular intersection [38]. The variation of the patient’s response to treatment and the variation in side effects to such treatment is the justifying reason for the recognition of the biological markers to predict the effectiveness of each treatment in each patient. Presence of anti-AChR antibodies is a beneficial biomarker in the diagnosis of MG. Still, it cannot judge disease severity as no specific correlation was found between MG severity and anti-AChR antibodies level [39]. MiR-323b-3p, −409-3p, −485-3p, −181d-5p, and − 340-3p has been predicted and suggested as response biomarker to project immunosuppressive drug sensitivity in MG patients.
The miRNAs can be tested in the blood, which would make it a potent response biomarker for treatment response, and any patient detected not to respond as expected will be addressed to other treatments thereby increasing cost-effectiveness. MiR-323b-3p, −409-3p and − 485-3p were downregulated in Non-responding patients while miRNA-181d-5p, and − 340-3p were upregulated in the Non-responding patients [39, 40]. A significant association has been identified between patient’s response to azathioprine and two haplotypes, the TPMT3E haplotype in the thiopurine S-methyltransferase and a haplotype in the ATP-binding cassette sub-family C member 6 transporter. The glucocorticoid therapy non-responsive MG patients were found to possess a genetic variant in the secreted phosphoprotein 1 (SPP1) gene encoding osteopontin, which associates it with the non-responsive group [40].
Pernicious anemia (PA), is an autoimmune disease which results from a long-standing infection by Helicobacter pylori and the end-stage of atrophic body gastritis (ABG). The condition which is still active gradually phased out by an autoimmunity reaction that depletes the gastric mucosa irreversibly. The deficiency of vitamin B12 has been implicated in the etiology also. Therefore the goal of a clinician in treating pernicious anemia may be to avert the signs and symptoms of anemia itself, manage its complications such as damage to the nerve and heart tissues, and identifying the specific cause where precision medicine comes in [41]. The National Heart, Lung, and Blood Institute (NHLBI) are currently carrying out basic and clinical researches that could incorporate precision medicine and improve the treatment of the condition.
Rheumatoid arthritis (RA) is a heterogeneous disease which can range from mild, self-limiting arthritis to fast progressive joint damage. It is triggered by a complex interaction between the human genetic makeup and the environment. Still, both environmental influence and genetics cannot exhaustively account for the heterogenic clinical features of the disease condition. It is also characterized by synovial hyperplasia and joint destruction, which can lead to joint deformity or [42].
Currently, the treatment of RA is based on the control of inflammation with which an effective therapy that comes early ensures a drastic reduction in the risk of joint damage, mortality and disability. As of 2017, major researches has focused on the identification of biomarkers that can predict patient’s response to only Methotrexate (MTX) which is the first non-biologic therapeutic agent administered. Also, TNF inhibitors (TNFi) has been established to be ineffective in about 30% of patients but remains the first choice of available biologic therapeutic agents. Solute carrier family 19 member 1 (SLC19A1) gene possess the most consistent and relevant evidence. It is one of the many transport carriers that allow the transport of MTX into the cell [43].
Anti- CCP antibodies a genomic marker associated with poor prognosis as it relates to the severity of disease and the extent of damage caused on the joint, HLA-DRB1 alleles coding for shared epitope is another marker for severity in RA [44].
Sjögren’s syndrome (SS) is a form of B cell hypersensitivity which is manifested in the formation of excess autoantibodies and a strong propensity for NHL of B cell emergence [45]. About 5% of patients of primary SS are at risk of lymphoma development. However, it is vital to have a specific biomarker to identify such patient early to be able to monitor and detect early and select appropriate therapy. The diagnostic biomarkers will guide in the diagnosis, and the predictive biomarkers are meant to show another aspect of clinical decision. Cytopenias is an established prognostic biomarker for the development of lymphoma [46]. A lot of proposed biomarkers in the assessment of SS are yet to be confirmed in more extensive studies before adoption into clinical use [47].
The systemic lupus erythematosus (SLE) has a broad spectrum of signs and symptoms which varies among patients and involves numerous organs with skin, joints, kidneys, lungs and CNS included. It is a chronic inflammatory autoimmune disease [48]. An association has been established between SLE and human leukocyte antigen (HLA) haplotypes (HLA-DR3; DR9; DR15; DQA1*0101 especially). The extensive association has also been found between vitamin D matching up with serum concentrations and vitamin D-receptor genomic binding domains [49].
The type 1 diabetes (T1D) takes place as a result of autoimmune beta-cell destruction, which leads to insufficient production of insulin and results in hyperglycemia [50]. Although the role of precision medicine in type 1 diabetes is not well defined, patient with T1D severity varies with difference in their pancreatic autoantibodies profile and the rate at which their beta cells destroy [51].
In genetic studies (an important feature of precision medicine), identification of over 50 genetic signals in notably HLA region has been found to influence T1D predisposition [52]. The diagnostic biomarkers (serum biomarkers) use in the diagnosis of T1D includes the combination of glucose, C-peptide, glycated molecules and autoantibodies established for T1D. Still, these molecules often mark the late stage of the disease [53].
So far, advance in genomic research introduces the administration of islet autoantigens or peptides into a recipient with the risk of T1D; these studies suggest promising changes in immune regulation of islet autoimmunity. The challenges remain dosing frequency, dosage, route of administration, and adjuvants use.
A systemic follow up of variant genes like the TNFRSF1A that is connected with multiple sclerosis risk should be closely investigated by researchers. This gene could give an essential perception of the etiology of multiple sclerosis and new treatment strategies.
Myasthenia gravis-related loci may display their involvement in the pathogenesis of immune disease by increasing immune response, repression of the mechanism involved in immune suppression, alteration of procedure that differentiates between autologous and heterologous molecular configuration through immune tolerance, therefore investigations into Single nucleotide polymorphisms (SNPs) in the general population that is associated with Myasthenia gravis will improve diagnosis, therapy and its outcome.
Genome editing technologies have been used with a degree of success in the treatment of sickle cell disease and β-thalassemia, this could be introduced into the precise treatment of pernicious anemia with proper study of the gene encoding for mitochondrial transport of vitamin B12.
Rheumatoid arthritis research should focus on discovering more associated genes and their resultant effects. Transcriptomic and epigenomic strategies should also be used in discovering biomarkers of response to treatments and pathways that are related to therapies. Integration of genetic, clinical and environmental data are also crucial in achieving the aim of precision medicine in the treatment of rheumatoid arthritis.
Selection of novel treatments could be achieved for sjogren syndrome by identification of genetic risk factors like that of profound interferon signaling pathway by IRF5 and STAT 4 genes.
Prevention of systemic lupus erythematosus by assaying genetic profile, developing new biomarkers of immune activation and alteration is the precise future treatment of this condition.
Investigations into genes and pathways of type 1 diabetes may reveal on time the pathogenic role of the destruction of β-cell and production of clinical disease by the innate and adaptive immune system. Type 1 Diabetes Genetics Consortium (T1DGC) international have resources that could help in diagnosis, interventions, and monitoring outcomes of treatment of type 1 diabetes.
As the era of ‘Big Health Data’ continues, it is essential for the diagnosis, prognosis and treatment monitoring efforts on autoimmune diseases to take advantage of the data and different machine learning and deep learning algorithms to establish patterns and clusters within the disease groups. This will help in the identification of more relevant biomarkers and also help in the easy transition of biomarker researches to the bedside.
Indeed, the application of precision medicine in autoimmune diseases depends on the progress of next-generation sequencing program, which at the same time will strive to provide not only a whole-exome, or transcriptome, but at an exact process that is cost-efficient.
The information provided by the Genomics data is an indispensable component of precision medicine as it holds the key to the explanation in individual variability and evolution [54]. But, the clinical use of genomic data still needs to be improved on to overcome challenges stated by Kim et al. [55] like:
The incongruity between the form of genomic and clinical information: as a result of extensive (several tens of gigabytes of sequence) data in the genomic data, clinical data cannot be processed in the clinical practice without additional processing [55, 56].
The difference in the properties of genomic data and observational data used in the clinical settings: given that the genomic workflows hold a large number of data, data obtained from this workflows is undoubtedly different from systems parallel to the clinical plan [57].
Difficulty in mapping the genomic and clinical data for medical interpretation: as seen in the case of targeted sequencing, where most data are processed before medical analysis [58].
Also, there is no international validation for biomarkers in use; there is a need for international collaboration to validate biomarkers presently in existence.
Overcoming these challenges will open up more opportunities for the use of genomic data in clinical practices.
The authors declare no conflict of interest.
IntechOpen books are indexed by the following abstracting and indexing services:
",metaTitle:"Indexing and Abstracting",metaDescription:"IntechOpen was built by scientists, for scientists. We understand the community we serve, but to bring an even better service to the table for IntechOpen Authors and Academic Editors, we partnered with the leading companies and associations in the industry and beyond.",metaKeywords:null,canonicalURL:"/page/indexing-and-abstracting",contentRaw:'[{"type":"htmlEditorComponent","content":"Clarivate Web Of Science - Book Citation Index
\\n\\nCroatian Library (digital NSK)
\\n\\nOCLC (Online Computer Library Center) - WorldCat® Digital Collection Gateway
\\n\\n\\n\\n
\\n"}]'},components:[{type:"htmlEditorComponent",content:'
Clarivate Web Of Science - Book Citation Index
\n\nCroatian Library (digital NSK)
\n\nOCLC (Online Computer Library Center) - WorldCat® Digital Collection Gateway
\n\n\n\n
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"58592",title:"Dr.",name:"Arun",middleName:null,surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58592/images/1664_n.jpg",biography:"Arun K. Shanker is serving as a Principal Scientist (Plant Physiology) with the Indian Council of Agricultural Research (ICAR) at the Central Research Institute for Dryland Agriculture in Hyderabad, India. He is working with the ICAR as a full time researcher since 1993 and has since earned his Advanced degree in Crop Physiology while in service. He has been awarded the prestigious Member of the Royal Society of Chemistry (MRSC), by the Royal Society of Chemistry, London in 2015. Presently he is working on systems biology approach to study the mechanism of abiotic stress tolerance in crops. His main focus now is to unravel the mechanism of drought and heat stress response in plants to tackle climate change related threats in agriculture.",institutionString:null,institution:{name:"Indian Council of Agricultural Research",country:{name:"India"}}},{id:"4782",title:"Prof.",name:"Bishnu",middleName:"P",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4782/images/system/4782.jpg",biography:"Bishnu P. Pal is Professor of Physics at Mahindra École\nCentrale Hyderabad India since July 1st 2014 after retirement\nas Professor of Physics from IIT Delhi; Ph.D.’1975 from IIT\nDelhi; Fellow of OSA and SPIE; Senior Member IEEE;\nHonorary Foreign Member Royal Norwegian Society for\nScience and Arts; Member OSA Board of Directors (2009-\n11); Distinguished Lecturer IEEE Photonics Society (2005-\n07).",institutionString:null,institution:{name:"Indian Institute of Technology Delhi",country:{name:"India"}}},{id:"69653",title:"Dr.",name:"Chusak",middleName:null,surname:"Limsakul",slug:"chusak-limsakul",fullName:"Chusak Limsakul",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Prince of Songkla University",country:{name:"Thailand"}}},{id:"75563",title:"Dr.",name:"Farzana Khan",middleName:null,surname:"Perveen",slug:"farzana-khan-perveen",fullName:"Farzana Khan Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75563/images/system/75563.png",biography:"Dr Farzana Khan Perveen (FLS; Gold-Medallist) obtained her BSc (Hons) and MSc (Zoology: Entomology) from the University of Karachi, MAS (Monbush-Scholar; Agriculture: Agronomy) and from the Nagoya University, Japan, and PhD (Research and Course-works from the Nagoya University; Toxicology) degree from the University of Karachi. She is Founder/Chairperson of the Department of Zoology (DOZ) and Ex-Controller of Examinations at Shaheed Benazir Bhutto University (SBBU) and Ex-Founder/ Ex-Chairperson of DOZ, Hazara University and Kohat University of Science & Technology. \nShe is the author of 150 high impact research papers, 135 abstracts, 4 authored books and 8 chapters. She is the editor of 5 books and she supervised BS(4), MSc(50), MPhil(40), and Ph.D. (1) students. She has organized and participated in numerous international and national conferences and received multiple awards and fellowships. She is a member of research societies, editorial boards of Journals, and World-Commission on Protected Areas, International Union for Conservation of Nature. Her fields of interest are Entomology, Toxicology, Forensic Entomology, and Zoology.",institutionString:"Shaheed Benazir Bhutto University",institution:{name:"Shaheed Benazir Bhutto University",country:{name:"Pakistan"}}},{id:"23804",title:"Dr.",name:"Hamzah",middleName:null,surname:"Arof",slug:"hamzah-arof",fullName:"Hamzah Arof",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/23804/images/5492_n.jpg",biography:"Hamzah Arof received his BSc from Michigan State University, and PhD from the University of Wales. Both degrees were in electrical engineering. His current research interests include signal processing and photonics. Currently he is affiliated with the Department of Electrical Engineering, University of Malaya, Malaysia.",institutionString:null,institution:{name:"University of Malaya",country:{name:"Malaysia"}}},{id:"41989",title:"Prof.",name:"He",middleName:null,surname:"Tian",slug:"he-tian",fullName:"He Tian",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"East China University of Science and Technology",country:{name:"China"}}},{id:"33351",title:null,name:"Hendra",middleName:null,surname:"Hermawan",slug:"hendra-hermawan",fullName:"Hendra Hermawan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/33351/images/168_n.jpg",biography:null,institutionString:null,institution:{name:"Institut Teknologi Bandung",country:{name:"Indonesia"}}},{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Osaka University",country:{name:"Japan"}}},{id:"45747",title:"Dr.",name:"Hsin-I",middleName:null,surname:"Chang",slug:"hsin-i-chang",fullName:"Hsin-I Chang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"National Chiayi University",country:{name:"Taiwan"}}},{id:"61581",title:"Dr.",name:"Joy Rizki Pangestu",middleName:null,surname:"Djuansjah",slug:"joy-rizki-pangestu-djuansjah",fullName:"Joy Rizki Pangestu Djuansjah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61581/images/237_n.jpg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"94249",title:"Prof.",name:"Junji",middleName:null,surname:"Kido",slug:"junji-kido",fullName:"Junji Kido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Yamagata University",country:{name:"Japan"}}},{id:"12009",title:"Dr.",name:"Ki Young",middleName:null,surname:"Kim",slug:"ki-young-kim",fullName:"Ki Young Kim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12009/images/system/12009.jpg",biography:"Http://m80.knu.ac.kr/~doors",institutionString:null,institution:{name:"National Cheng Kung University",country:{name:"Taiwan"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5699},{group:"region",caption:"Middle and South America",value:2,count:5172},{group:"region",caption:"Africa",value:3,count:1689},{group:"region",caption:"Asia",value:4,count:10244},{group:"region",caption:"Australia and Oceania",value:5,count:888},{group:"region",caption:"Europe",value:6,count:15650}],offset:12,limit:12,total:10244},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish",topicId:"5"},books:[{type:"book",id:"10358",title:"Silage - Recent Advances and New Perspectives",subtitle:null,isOpenForSubmission:!0,hash:"1e33f63e9311af352daf51d49f0a3aef",slug:null,bookSignature:"Dr. Juliana Oliveira and Dr. Edson Mauro Santos",coverURL:"https://cdn.intechopen.com/books/images_new/10358.jpg",editedByType:null,editors:[{id:"180036",title:"Dr.",name:"Juliana",surname:"Oliveira",slug:"juliana-oliveira",fullName:"Juliana Oliveira"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10238",title:"Food Packaging",subtitle:null,isOpenForSubmission:!0,hash:"891ee7ffd87b72cf155fcdf9c8ae5d1a",slug:null,bookSignature:"Dr. Norizah Mhd Sarbon",coverURL:"https://cdn.intechopen.com/books/images_new/10238.jpg",editedByType:null,editors:[{id:"246000",title:"Dr.",name:"Norizah",surname:"Mhd Sarbon",slug:"norizah-mhd-sarbon",fullName:"Norizah Mhd Sarbon"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9706",title:"Goat Science - Environment, Health and Economy",subtitle:null,isOpenForSubmission:!0,hash:"7e5d45badb49806d949ad1475e3a0ef0",slug:null,bookSignature:"Prof. Sándor Kukovics",coverURL:"https://cdn.intechopen.com/books/images_new/9706.jpg",editedByType:null,editors:[{id:"25894",title:"Prof.",name:"Sándor",surname:"Kukovics",slug:"sandor-kukovics",fullName:"Sándor Kukovics"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9710",title:"Olive Oil - New Perspectives and Applications",subtitle:null,isOpenForSubmission:!0,hash:"2f673efc0d0213f2d937fc89e65a24df",slug:null,bookSignature:"Dr. Muhammad Akram",coverURL:"https://cdn.intechopen.com/books/images_new/9710.jpg",editedByType:null,editors:[{id:"215436",title:"Dr.",name:"Muhammad",surname:"Akram",slug:"muhammad-akram",fullName:"Muhammad Akram"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9715",title:"Botany - Recent Advances and Applications",subtitle:null,isOpenForSubmission:!0,hash:"3e59225e9e029129a60fe724004b8d24",slug:null,bookSignature:"Prof. Bimal Kumar Ghimire",coverURL:"https://cdn.intechopen.com/books/images_new/9715.jpg",editedByType:null,editors:[{id:"94560",title:"Prof.",name:"Bimal Kumar",surname:"Ghimire",slug:"bimal-kumar-ghimire",fullName:"Bimal Kumar Ghimire"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9651",title:"Cereal Grains",subtitle:null,isOpenForSubmission:!0,hash:"918540a77975243ee748770aea1f4af2",slug:null,bookSignature:"Dr. Aakash Goyal",coverURL:"https://cdn.intechopen.com/books/images_new/9651.jpg",editedByType:null,editors:[{id:"97604",title:"Dr.",name:"Aakash",surname:"Goyal",slug:"aakash-goyal",fullName:"Aakash Goyal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10236",title:"Plasmodium Species and Drug Resistance",subtitle:null,isOpenForSubmission:!0,hash:"964a389525d1147af3e527c056ac1a73",slug:null,bookSignature:"Dr. Rajeev K. Tyagi",coverURL:"https://cdn.intechopen.com/books/images_new/10236.jpg",editedByType:null,editors:[{id:"269120",title:"Dr.",name:"Rajeev K.",surname:"Tyagi",slug:"rajeev-k.-tyagi",fullName:"Rajeev K. Tyagi"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8950",title:"Birds - Challenges and Opportunities for Business, Conservation and Research",subtitle:null,isOpenForSubmission:!0,hash:"404a05af45e47e43871f4a0b1bedc6fd",slug:null,bookSignature:"Dr. Heimo Juhani Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/8950.jpg",editedByType:null,editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9662",title:"Vegetation Index and Dynamics",subtitle:null,isOpenForSubmission:!0,hash:"0abf2a59ee63fc1ba4fb64d77c9b1be7",slug:null,bookSignature:"Dr. Eusebio Cano Carmona, Dr. Ricardo Quinto Canas, Dr. Ana Cano Ortiz and Dr. Carmelo Maria Musarella",coverURL:"https://cdn.intechopen.com/books/images_new/9662.jpg",editedByType:null,editors:[{id:"87846",title:"Dr.",name:"Eusebio",surname:"Cano Carmona",slug:"eusebio-cano-carmona",fullName:"Eusebio Cano Carmona"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:16},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:6},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:4},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:56},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:9},popularBooks:{featuredBooks:[{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5143},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editedByType:"Edited by",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editedByType:"Edited by",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9569",title:"Methods in Molecular Medicine",subtitle:null,isOpenForSubmission:!1,hash:"691d3f3c4ac25a8093414e9b270d2843",slug:"methods-in-molecular-medicine",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/9569.jpg",editedByType:"Edited by",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editedByType:"Edited by",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editedByType:"Edited by",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8063",title:"Food Security in Africa",subtitle:null,isOpenForSubmission:!1,hash:"8cbf3d662b104d19db2efc9d59249efc",slug:"food-security-in-africa",bookSignature:"Barakat Mahmoud",coverURL:"https://cdn.intechopen.com/books/images_new/8063.jpg",editedByType:"Edited by",editors:[{id:"92016",title:"Dr.",name:"Barakat",middleName:null,surname:"Mahmoud",slug:"barakat-mahmoud",fullName:"Barakat Mahmoud"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10118",title:"Plant Stress Physiology",subtitle:null,isOpenForSubmission:!1,hash:"c68b09d2d2634fc719ae3b9a64a27839",slug:"plant-stress-physiology",bookSignature:"Akbar Hossain",coverURL:"https://cdn.intechopen.com/books/images_new/10118.jpg",editedByType:"Edited by",editors:[{id:"280755",title:"Dr.",name:"Akbar",middleName:null,surname:"Hossain",slug:"akbar-hossain",fullName:"Akbar Hossain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editedByType:"Edited by",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editedByType:"Edited by",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editedByType:"Edited by",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"198",title:"Physical Therapy",slug:"physical-therapy",parent:{title:"Medicine",slug:"medicine"},numberOfBooks:3,numberOfAuthorsAndEditors:58,numberOfWosCitations:0,numberOfCrossrefCitations:13,numberOfDimensionsCitations:17,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"physical-therapy",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7543",title:"Physical Therapy Effectiveness",subtitle:null,isOpenForSubmission:!1,hash:"96855ef0bdc30d253f8fd74aa6cfd363",slug:"physical-therapy-effectiveness",bookSignature:"Mario Bernardo-Filho, Danúbiada Cunha de Sá-Caputo and Redha Taiar",coverURL:"https://cdn.intechopen.com/books/images_new/7543.jpg",editedByType:"Edited by",editors:[{id:"157376",title:"Prof.",name:"Mario",middleName:null,surname:"Bernardo-Filho",slug:"mario-bernardo-filho",fullName:"Mario Bernardo-Filho"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6772",title:"Occupational Therapy",subtitle:"Therapeutic and Creative Use of Activity",isOpenForSubmission:!1,hash:"0f6de90c02282919494d6254e473defe",slug:"occupational-therapy-therapeutic-and-creative-use-of-activity",bookSignature:"Meral Huri",coverURL:"https://cdn.intechopen.com/books/images_new/6772.jpg",editedByType:"Edited by",editors:[{id:"171525",title:"Dr.",name:"Meral",middleName:null,surname:"Huri",slug:"meral-huri",fullName:"Meral Huri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5711",title:"Occupational Therapy",subtitle:"Occupation Focused Holistic Practice in Rehabilitation",isOpenForSubmission:!1,hash:"38180e287b6cb09b8002b7ab485de2c2",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",bookSignature:"Meral Huri",coverURL:"https://cdn.intechopen.com/books/images_new/5711.jpg",editedByType:"Edited by",editors:[{id:"171525",title:"Dr.",name:"Meral",middleName:null,surname:"Huri",slug:"meral-huri",fullName:"Meral Huri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:3,mostCitedChapters:[{id:"55163",doi:"10.5772/intechopen.68799",title:"Virtual Reality and Occupational Therapy",slug:"virtual-reality-and-occupational-therapy",totalDownloads:2016,totalCrossrefCites:3,totalDimensionsCites:4,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Orkun Tahir Aran, Sedef Şahin, Berkan Torpil, Tarık Demirok and\nHülya Kayıhan",authors:[{id:"172938",title:"Prof.",name:"Hulya",middleName:null,surname:"Kayihan",slug:"hulya-kayihan",fullName:"Hulya Kayihan"},{id:"183079",title:"Ph.D.",name:"Sedef",middleName:null,surname:"Şahin",slug:"sedef-sahin",fullName:"Sedef Şahin"},{id:"196848",title:"M.Sc.",name:"Orkun Tahir",middleName:null,surname:"Aran",slug:"orkun-tahir-aran",fullName:"Orkun Tahir Aran"},{id:"197159",title:"Mr.",name:"Tarık",middleName:null,surname:"Demirok",slug:"tarik-demirok",fullName:"Tarık Demirok"},{id:"197312",title:"M.Sc.",name:"Berkan",middleName:null,surname:"Torpil",slug:"berkan-torpil",fullName:"Berkan Torpil"}]},{id:"55024",doi:"10.5772/intechopen.68463",title:"Occupational Therapy in Oncology and Palliative Care",slug:"occupational-therapy-in-oncology-and-palliative-care",totalDownloads:1908,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Sedef Şahin, Semin Akel and Meral Zarif",authors:[{id:"183079",title:"Ph.D.",name:"Sedef",middleName:null,surname:"Şahin",slug:"sedef-sahin",fullName:"Sedef Şahin"},{id:"183078",title:"Dr.",name:"Burcu Semin",middleName:null,surname:"Akel",slug:"burcu-semin-akel",fullName:"Burcu Semin Akel"},{id:"198859",title:"Dr.",name:"Meral",middleName:null,surname:"Zarif",slug:"meral-zarif",fullName:"Meral Zarif"}]},{id:"56049",doi:"10.5772/intechopen.69101",title:"Measurement of Participation: The Role Checklist Version 3: Satisfaction and Performance",slug:"measurement-of-participation-the-role-checklist-version-3-satisfaction-and-performance",totalDownloads:1872,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Patricia J. Scott, Kelsey McKinney, Jeff Perron, Emily Ruff and Jessica\nSmiley",authors:[{id:"195495",title:"Dr.",name:"Patricia J",middleName:null,surname:"Scott",slug:"patricia-j-scott",fullName:"Patricia J Scott"},{id:"208801",title:"Dr.",name:"Kelsey G.",middleName:null,surname:"McKinney",slug:"kelsey-g.-mckinney",fullName:"Kelsey G. McKinney"},{id:"208802",title:"Mr.",name:"Jeffrey M.",middleName:null,surname:"Perron",slug:"jeffrey-m.-perron",fullName:"Jeffrey M. Perron"},{id:"208803",title:"Dr.",name:"Emily G.",middleName:null,surname:"Ruff",slug:"emily-g.-ruff",fullName:"Emily G. Ruff"},{id:"208804",title:"Dr.",name:"Jessica L.",middleName:null,surname:"Smiley",slug:"jessica-l.-smiley",fullName:"Jessica L. Smiley"}]}],mostDownloadedChaptersLast30Days:[{id:"55355",title:"Assistive Technology in Occupational Therapy",slug:"assistive-technology-in-occupational-therapy",totalDownloads:4222,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Gokcen Akyurek, Sinem Kars, Zeynep Celik, Ceren Koc and Özge\nBuket Cesim",authors:[{id:"197265",title:"Dr.",name:"Gokcen",middleName:null,surname:"Akyurek",slug:"gokcen-akyurek",fullName:"Gokcen Akyurek"},{id:"205199",title:"Dr.",name:"Sinem",middleName:null,surname:"Kars",slug:"sinem-kars",fullName:"Sinem Kars"},{id:"205200",title:"Dr.",name:"Zeynep",middleName:null,surname:"Celik",slug:"zeynep-celik",fullName:"Zeynep Celik"},{id:"205201",title:"Dr.",name:"Ceren",middleName:null,surname:"Koc",slug:"ceren-koc",fullName:"Ceren Koc"},{id:"205203",title:"Ms.",name:"Özge Buket",middleName:null,surname:"Cesim",slug:"ozge-buket-cesim",fullName:"Özge Buket Cesim"}]},{id:"70122",title:"Parkinson’s Disease Rehabilitation: Effectiveness Approaches and New Perspectives",slug:"parkinson-s-disease-rehabilitation-effectiveness-approaches-and-new-perspectives",totalDownloads:804,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"physical-therapy-effectiveness",title:"Physical Therapy Effectiveness",fullTitle:"Physical Therapy Effectiveness"},signatures:"Luciana Auxiliadora de Paula Vasconcelos",authors:[{id:"98546",title:"Dr.",name:"Luciana Auxiliadora",middleName:null,surname:"De Paula Vasconcelos",slug:"luciana-auxiliadora-de-paula-vasconcelos",fullName:"Luciana Auxiliadora De Paula Vasconcelos"}]},{id:"55080",title:"Life Skills in Occupational Therapy",slug:"life-skills-in-occupational-therapy",totalDownloads:4566,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Hatice Abaoğlu, Özge Buket Cesim, Sinem Kars and Zeynep Çelik",authors:[{id:"205199",title:"Dr.",name:"Sinem",middleName:null,surname:"Kars",slug:"sinem-kars",fullName:"Sinem Kars"},{id:"205200",title:"Dr.",name:"Zeynep",middleName:null,surname:"Celik",slug:"zeynep-celik",fullName:"Zeynep Celik"},{id:"205203",title:"Ms.",name:"Özge Buket",middleName:null,surname:"Cesim",slug:"ozge-buket-cesim",fullName:"Özge Buket Cesim"},{id:"197551",title:"Dr.",name:"Hatice",middleName:null,surname:"Abaoğlu",slug:"hatice-abaoglu",fullName:"Hatice Abaoğlu"}]},{id:"62210",title:"Occupational Therapy’s Role in the Treatment of Children with Autism Spectrum Disorders",slug:"occupational-therapy-s-role-in-the-treatment-of-children-with-autism-spectrum-disorders",totalDownloads:1638,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"occupational-therapy-therapeutic-and-creative-use-of-activity",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Therapeutic and Creative Use of Activity"},signatures:"Bryan M. Gee, Amy Nwora and Theodore W. Peterson",authors:null},{id:"60928",title:"Animal-Assisted Therapy in Occupational Therapy",slug:"animal-assisted-therapy-in-occupational-therapy",totalDownloads:1092,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"occupational-therapy-therapeutic-and-creative-use-of-activity",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Therapeutic and Creative Use of Activity"},signatures:"Sedef Şahin, Barkın Kose and Meral Zarif",authors:[{id:"183079",title:"Ph.D.",name:"Sedef",middleName:null,surname:"Şahin",slug:"sedef-sahin",fullName:"Sedef Şahin"},{id:"198859",title:"Dr.",name:"Meral",middleName:null,surname:"Zarif",slug:"meral-zarif",fullName:"Meral Zarif"},{id:"199029",title:"B.Sc.",name:"Barkın",middleName:null,surname:"Kose",slug:"barkin-kose",fullName:"Barkın Kose"}]},{id:"62493",title:"Occupational Therapy in Forensic Settings",slug:"occupational-therapy-in-forensic-settings",totalDownloads:1479,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"occupational-therapy-therapeutic-and-creative-use-of-activity",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Therapeutic and Creative Use of Activity"},signatures:"Esma Ozkan, Sümeyye Belhan, Mahmut Yaran and Meral Zarif",authors:null},{id:"55018",title:"Psychomotor Therapy for Patients with Severe Mental Health Disorders",slug:"psychomotor-therapy-for-patients-with-severe-mental-health-disorders",totalDownloads:1518,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Michel Probst",authors:[{id:"196227",title:"Prof.",name:"Michel",middleName:null,surname:"Probst",slug:"michel-probst",fullName:"Michel Probst"}]},{id:"55024",title:"Occupational Therapy in Oncology and Palliative Care",slug:"occupational-therapy-in-oncology-and-palliative-care",totalDownloads:1908,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Sedef Şahin, Semin Akel and Meral Zarif",authors:[{id:"183079",title:"Ph.D.",name:"Sedef",middleName:null,surname:"Şahin",slug:"sedef-sahin",fullName:"Sedef Şahin"},{id:"198859",title:"Dr.",name:"Meral",middleName:null,surname:"Zarif",slug:"meral-zarif",fullName:"Meral Zarif"},{id:"183078",title:"Dr.",name:"Burcu Semin",middleName:null,surname:"Akel",slug:"burcu-semin-akel",fullName:"Burcu Semin Akel"}]},{id:"55989",title:"Occupational Therapy for Elderly People",slug:"occupational-therapy-for-elderly-people",totalDownloads:1714,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Onur Altuntaş, Berkan Torpil and Mine Uyanik",authors:[{id:"196235",title:"Ph.D.",name:"Onur",middleName:null,surname:"Altuntaş",slug:"onur-altuntas",fullName:"Onur Altuntaş"},{id:"197312",title:"M.Sc.",name:"Berkan",middleName:null,surname:"Torpil",slug:"berkan-torpil",fullName:"Berkan Torpil"},{id:"204945",title:"Prof.",name:"Mine",middleName:null,surname:"Uyanık",slug:"mine-uyanik",fullName:"Mine Uyanık"}]},{id:"55049",title:"Community Participation in People with Disabilities",slug:"community-participation-in-people-with-disabilities",totalDownloads:1525,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",title:"Occupational Therapy",fullTitle:"Occupational Therapy - Occupation Focused Holistic Practice in Rehabilitation"},signatures:"Gokcen Akyurek and Gonca Bumin",authors:[{id:"197265",title:"Dr.",name:"Gokcen",middleName:null,surname:"Akyurek",slug:"gokcen-akyurek",fullName:"Gokcen Akyurek"},{id:"32431",title:"Prof.",name:"Gonca",middleName:null,surname:"Bumin",slug:"gonca-bumin",fullName:"Gonca Bumin"}]}],onlineFirstChaptersFilter:{topicSlug:"physical-therapy",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/30448/robert-stockley",hash:"",query:{},params:{id:"30448",slug:"robert-stockley"},fullPath:"/profiles/30448/robert-stockley",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()