Hyperekplexia

Neurological Disorders and Epilepsy among Adolescents

Adolescence includes phases of both significant social role shifts and biological growth, both of which have evolved over the previous 100 years. A relatively prevalent neurologic condition throughout adolescence is epilepsy. Growth, hormonal, psychological, and social circumstances all undergo significant change during adolescence. It can be extremely challenging for many young women with epilepsy to manage the developmental and emotional challenges of adolescence while still having to deal with the reality of seizures, medication, stigma, and restriction. These young women's everyday functioning and quality of life are further impacted by the additional load of comorbidities like depression. It is crucial to spend time with these teenagers discussing the effects of epilepsy and giving them the information and resources they need to succeed in regaining their confidence and control over their lives. Teenagers frequently struggle to embrace the chronic nature of their epilepsy and to take their medications as prescribed, which can lead to bodily harm and real or imagined barriers to employment and lower morale. Additionally, it was discovered that children and teenagers with epilepsy are more likely to exhibit depressive and anxious symptoms. Additionally, teenagers also suffer from other neurological disorders that are common but less reported, like multiple sclerosis. The aim of this chapter is to focus on some of the neurological diseases that are present mainly in the adolescent period mainly epilepsy and some other neurological diseases.

Molecular Mechanisms Implicated with Depression and Therapeutic Intervention

Depression is a pervasive, arduous psychological condition with profound neurological ramifications. The parameters for leveraging depression involve the diagnosis and evaluation of depression, the endorsement to implement substantiated therapies and rigorous follow-up of the patients. Many individuals suffering from depression undertake a recurring or persistent therapy that correlates to a decline in cognitive processing. The underpinnings of exact aetiology and pathogenesis of melancholy are probably the outcome of a variety of mechanisms. These include physiological, behavioural, and socio-economic variables, all playing their roles. Multiple refinements to the treatments encompassing therapies, medications and medical interventions are employed, in relation to effective approaches reassuring the brighter side. In this chapter, we discuss more integrative and multifaceted aspects of psychological health, minimizing the segmented understanding to achieve a consensus on multiple possibilities for effective interventions.

The Geriatric COVID Patient

The COVID-19 pandemic resulted in a significant impact on healthcare across the world. The pandemic is caused by the coronavirus SARS-CoV-2 and is transmitted through respiratory secretions. The geriatric population comprised most morbidities and mortalities related to COVID-19. Common symptoms include fever, cough, dyspnea, myalgia, and culminating in acute hypoxic respiratory failure and acute myocardial injury. Geriatric patients with COVID-19 who require surgery are at a greater risk of postoperative complications. An assessment of the risks and benefits of surgical intervention relies on the degree of COVID-19 pathology and the type of surgery whether emergent or elective. The presence of COVID-19 does not warrant a change in the modality of anesthesia that would be performed for any given surgery in the absence of COVID-19.

Female Geriatric Patients

Men and women are created equal, but there are some biological differences between the two sexes that should be considered in the perioperative period to provide safe and equitable care. This chapter highlights specific anatomical differences between men and women and discusses conditions by system that are more prevalent among female geriatric patients. Plus, it briefly discusses particular sex differences in the pharmacokinetics of some drugs.

Anesthetic Considerations for Patients with Chronic Neurologic Disorders

Chronic neurological disorders encompass a broad range of challenges for the surgical and anesthesiology team in the perioperative setting. According to the World Population Prospects 2019, by 2050, 1 in 6 people will be over 65, from 1 in 11 in 2019 [1]. As our population continues to age, our understanding and ability to provide medical and surgical services must improve as well. Perioperative strokes are rare, but they can greatly impact a patient's recovery and function when they occur. Dementia strongly predicts postoperative complications, higher hospital costs, and 30- day mortality [2]. Patients with Parkinson’s disease are at a higher risk of perioperative medical and surgical complications not to mention specific medication regimens that need to be adjusted to avoid worsening symptomatology. Although rare, a patient presenting with Amyotrophic lateral sclerosis (ALS), can present with a broad range of neurologic symptoms, and cardiovascular and pulmonary dysfunction that can be daunting for any anesthesia provider. In this chapter, we will explore the comprehensive approach to managing chronic neurologic disorders, including multidisciplinary care, early identification of potential complications, specialized medication management, and intraoperative considerations.

Geriatric Pain Patient

Chronic pain is a major cause of physical disability, poor mental health, and decreased quality of life [1,2]. The burden of chronic pain is reflected in increased medical care utilization and consequently increased healthcare costs, which are estimated at an astounding $560 billion per year [3]. CDC estimates from 2019 reveal that while 20.4% of adults in the USA live with chronic pain, the prevalence increases with advancing age [4]. 30.8% of people aged 65 years and above had chronic pain while 11.8% of them had high-impact chronic pain, which is defined as pain that causes significant restriction of self-care, social and work-related activities [5]. The impact of chronic pain is more severe in the elderly; older adults report poorer physical health and disability in comparison to younger adults [6-8]. Chronic pain in the elderly is also associated with poorer sleep, cognitive decline, dementia, and death [9-13]. With the projected increase in the elderly population in the US every year, the burden of chronic pain is only expected to increase. This chapter outlines the physiologic and pharmacologic changes that happen with ageing, the major causes of chronic pain in the elderly, as well as the myriad of treatment options available with a focus on pharmacotherapy, behavioral and alternative therapies, and interventional pain therapies. The focus of treatment is not only targeted towards reducing pain but special considerations should be made to minimize the cognitive effects of polypharmacy in light of multiple comorbidities and promote mental well-being and functional independence [14].

Pulmonary Hypertension and Geriatric Patients

Pulmonary hypertension is a common and life-threatening condition, characterized by elevated blood pressure in the pulmonary artery, which supplies blood to the lungs. This condition is typically classified into five groups based on etiology. The etiology of pulmonary hypertension in the elderly is complex and multifactorial. Some of the common causes of pulmonary hypertension in this population include leftsided heart disease, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and pulmonary embolism. The initial evaluation determines the cause, which guides the appropriate treatment. The most common causes in the elderly arise from left heart disease and the sequela of COPD. Long-standing disease can result in pulmonary hypertension leading to right heart failure and potentially catastrophic consequences in a patient population with decreased physiologic reserve. Anesthesia and surgery in patients with pulmonary hypertension pose a significant risk of complications including death. Acute right ventricular decompensation can result from various physiological changes induced by anesthesia and sedation. Adequate risk assessment and individualized care are essential components of care. Efforts to avoid increases in pulmonary vascular resistance are keys to anesthetic management. However, despite the increase of pulmonary hypertension in the geriatric population, limited studies are dedicated to this group.

The NLRP3 Inflammasome as a Target for Antiinflammatory Drugs

The Nod-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the nonspecific immune response to inflammatory triggers such as cellular infections, injury, or stressors, and it has also been associated with several inflammation-related diseases. NLRP3 inflammasome activation results in the production of proinflammatory cytokines, contributing to an increased risk of inflammatory conditions, such as cardiovascular, metabolic, infectious, and neurodegenerative diseases. Several signaling pathways and cellular events involved in the NLRP3 inflammasome assembly and activation have been studied, and inhibitory mechanisms have been identified. NLRP3 inflammasome inhibition decreases inflammation and inflammasome-mediated cell death. In prospecting for novel anti-inflammatory therapeutics, signaling molecules upstream or downstream on the NLRP3 inflammasome pathway can serve as viable drug targets. Effective inhibition of these molecules culminates in the downregulation of the expression of proinflammatory cytokines like interleukin-1beta (IL-1β) and IL-18. This chapter elucidates the various classes of NLRP3 inflammasome inhibitors, their resultant anti-inflammatory effects, and various mechanisms of action.

Pathogenesis of Atherosclerosis and Coronary Heart Disease: Epidemiology, Diagnostic Biomarkers and Prevention by Nutraceuticals, Functional Foods, and Plant-Derived Therapies

Atherosclerosis is characterized by hardening/narrowing of arteries and reduction of blood flow to vital organs. Animal models and human research show that endothelial dysfunction and plaque development precede the pathogenesis of atherosclerosis, and related coronary heart disease, neurological, and renal disorders. Cardiac CT-scans are used to detect atherosclerosis. Early diagnosis of atherosclerosis reduces mortality, morbidity, and healthcare expenditures. Biomarkers like C-reactive protein, IL-6, IL-8, phospholipase A2, cardiac troponin, MicroRNA, miR-21, and other endothelial inflammation biomarkers are novel targets for monitoring atherosclerosisrelated cardiovascular disorders. Anti-platelet and anti-cholesterol drugs are used in the treatment of atherogenesis and blood vessel clots. However, cholesterol-lowering drugs may cause serious adverse effects. Thus, safe and cost-effective non-pharmacological anti-atherogenic and anticoagulant therapies are urgently needed. Nutraceuticals, functional foods, plant-derived therapies, antioxidant/anti-inflammation, foods/fruits/vegetables, and lifestyle changes (e.g., physical activity, less alcohol, smoking cessation) reduce atherogenesis, diabetes mellitus, obesity, hypertension, LDL, and C-reactive protein in all age groups, especially younger people. Overwhelming evidence suggests that regular physical activity (30 min/day), cessation of cigarette smoking, and consumption of antioxidant nutraceuticals rich in flavonoids and retinoids, fresh vegetables and fruits, omega-3 PUFA, culinary spices, probiotics, Mediterranean-type diet, and “DASH DIET” lower the risk of atherogenesis and cardiovascular diseases. This review summarizes current advances in the diagnosis and management of atherosclerosis and related cardiovascular illnesses with plant-based and wholesome diets, including the Mediterranean diet, DASH DIET, and lifestyle changes. New preventative measures and alternative therapies, including dietary interventions and plant-based foods may be the most cost-effective ways to manage atherosclerosis and cardiovascular illnesses.

The Role of Age in Pediatric Tumors of the Central Nervous System

Pediatric tumors of the central nervous system (CNS) are the second most common type of solid childhood cancer. As such, they have a major effect on the rates of morbidity and mortality in children. CNS tumors originate from abnormal cells in the brain and/or spinal cord, which can be classified as either benign or malignant. They can be further subdivided into different categories based on several principal aspects, such as tumor location, histopathology, and developmental age. Among these various characteristics, age is one of the most consequential determinants for CNS tumors. Specific groups between 0 and 21 years of age, for instance, have radically divergent landscapes in terms of their tumor incidence and unique biology. Depending on the age of the child, key case features may differ like the clinical evaluation, medical diagnosis and prognosis, recommended therapy and treatment courses, anticipated responses and tolerability to treatment, and management of side effects. Effective teamwork is another crucial component for the successful management of pediatric CNS tumors. In patient-and-family-centered care, ensuring a detailed education of the children and their families, as well as their involvement in the decision-making process where appropriate, is imperative. To determine the best available options for the patient, multidisciplinary medical teams will often deliberate over all of the possible procedures. The holistic care provided by these interprofessional collaborations for this vulnerable population will depend on the age of the child, in addition to the level of patient and family participation. Evidence shows that support and counseling of the patient and their family during the entire treatment process can have a significant impact on outcomes. This chapter will review the essential diagnostic and prognostic considerations of childhood CNS tumors, with special emphasis placed on favorable therapies and treatments, including in-depth discussions around the multi-faceted responses to treatment and the management of its side effects. In particular, this content will highlight the critical role that age, and interdisciplinary healthcare teams play in comprehensive disease management.

Promising Pharmaceutical Compounds of Marine Fishes: Their Chemistry and Therapeutic Applications

This chapter deals with the bioactive potential of the different groups of marine fishes viz. cartilaginous, bony, and jawless fish species.

References

Sexual Dysfunction

Phyto-nanoformulations for the Treatment of Clinical Diseases

Plant-derived drugs or formulations have always been explored because of

their lesser side effects and toxicities compared to synthetic drugs and they have been

widely used as traditional and complementary medicines for the management of many

diseases including cancer. The major challenges faced were the absorption of the plantderived

drugs, their stability, bioavailability, and transport to the intended sites inside

the body. Recent progress in nanotechnology has helped to minimize these limitations

and hence phyto-nanoformulations are slowly growing in preclinical trials as well as

clinical use. The use of various nanostructures such as nano-micelles, lipid

nanoparticles, carbon nanotubes, polymer nanoparticles, and nanoliposomes and

various types of drug delivery vehicles such as polybutylcyanoacrylate, polylactic-c-

-glycolic acid, and lactoferrin has immensely helped in increasing the effectiveness of

phytochemical drugs by increasing their stability, better pharmacokinetics and reducing

the toxicity and side effects. Phyto-nanoformulations having natural product

components such as curcumin, piperine, quercetin, berberine, scutellarin, baicalin,

stevioside, silybin, gymnemic acid, naringenin, capsicum oleoresin, emodin, and

resveratrol have been shown to improve the condition of patients diagnosed with

diseases such as neurodegenerative disorders, diabetes, infections, and cancer. Phyto

nanoformulations can also be used to treat disorders of the brain where the blood-brain

barrier is impervious to the drugs. These phyto-nanoformulations have been shown to

target several molecular cell-signaling and metabolic pathways. This chapter covers the

compositions of phyto-nanoformulations and how they have been used to control

several diseases.

Neurological Examination

A neurological exam, also called a neuro exam, is an evaluation of a person's nervous system that can be done in the physcians. It may be done with instruments, such as lights and reflex hammers. It usually does not cause any pain to the patient. The nervous system consists of the brain, the spinal cord, and the nerves from these areas. There are many aspects of this exam, including an assessment of motor and sensory skills, balance and coordination, mental status (the patient's level of awareness and interaction with the environment), reflexes, and functioning of the nerves. The extent of the exam depends on many factors, including the initial problem that the patient is experiencing, the age of the patient, and the condition of the patient.

Radiation from Mobile Phones and Cell Towers, Risks, and Protection

Modern life is strongly associated with new technologies such as telecommunication and wireless devices. These new technologies strongly affect the way people communicate, learn, train, think and solve their problems. Today, modern cell phones not only send and receive phone calls, but they also allow people to send and receive short messages, and e-mails, share photos and videos, write, edit and share documents, play games, listen to music, watch movies, surf the Internet, find an address using GPS (Global Positioning Systems) and use a wide range of applications. Given this consideration, excessive use of smartphones is associated with growing global concerns over the health effects of radiofrequency electromagnetic fields (RF-EMF) generated by these devices. As discussed by WHO, considering the very large number of people who use mobile phones, even a small increase in the risk of adverse health effects, either cancer or other health effects, could have key public health implications. WHO believes that research about these health effects is mostly focused on potential adverse effects of mobile phones, not their base stations, because the RF-EMF levels of mobile phones are 3 orders of magnitude higher than those of base stations. Therefore, in this chapter, due to the greater likelihood of adverse health effects of handsets, we mainly focused on reviewing the current scientific evidence on health risks associated with mobile phones. However, the health effects of RF-EMF exposure on people living in the proximity of mobile base stations are also reviewed.

Biological Functions of d- and f- Block Elements

Biological Functions of Elements of Main Groups

Meconium Stained Newborn

Meconium Stained Amniotic Fluid (MSAF) and Meconium Aspiration Syndrome (MAS) in newborn are commonly encountered by obstetricians and neonatologists world over, and more so in developing countries. MAS is a serious condition as it causes severe respiratory morbidity and complications like air leak, pneumothorax, Persistent Pulmonary Hypertension (PPHN), surfactant inactivation and death in many cases. There have been several changes in the management of pregnant mothers and their neonates, as well as in the endotracheal suctioning guidelines for babies born with MSAF ever since the pathogenesis of intra-uterine passage of meconium and meconium aspiration syndrome, and evidence on intervention outcomes became known. This chapter shall review the mechanism of meconium stained amniotic fluid, the pathophysiology of meconium aspiration syndrome and management of the newborn infant in the labor room, NICU and beyond, as per the present consensus. Potential newer therapies and drugs shall also be briefly addressed.

The Role of Integrated Services in the Care of Children and Young People with Neurodevelopmental Disorders and Co-Morbid Mental Health Difficulties: An International Perspective

Children and Young People (CYP) affected by Neurodevelopmental, Emotional, Behavioural and Intellectual Disorders (NDEBIDs) such as Attention Deficit and Hyperactive Disorder (ADHD) and Autism Spectrum Disorder (ASD) are at increased risk of other Mental Health (MH) difficulties such as anxiety and depression. Therefore, they require comprehensive and holistic services to meet their complex needs. However, many countries still offer them disjointed services involving different healthcare providers and professionals each looking at only one aspect of the CYP’s needs. To address this problem, the framework of “Integrated Care” is recommended as a template for providing comprehensive and joined-up care to meet the complex needs of these CYP with NDEBIDs and MH difficulties. This chapter aims to explore integrated care. It outlines the adverse impacts of disjointed care including: unnecessary multiple referrals, inefficient multiple assessments, delays in accessing required assessment and treatment, frustration and distress for affected CYP and their families and conflicts among professionals. Identified barriers to integrated care include problems with health planning, limited evidence-base, inter-professional difficulties related to different training and professional cultures and mental health stigma. The chapter highlights the benefits of integrated care including user satisfaction, the shortened path to point of care, systemic efficiencies and improved professional relationships. Finally, the chapter discusses the following desirable characteristics of integrated care: joint care commissioning, adequate ring-fenced funding, strategic leadership and planning, cross-training for professionals and good adherence to evidence-based protocols. Perspectives from Low and Middle-Income Countries (LMICs) were also discussed to acknowledge the international nature of the problem.

Immunomodulatory Plant Extracts and their Compounds. Evaluation of your Safety

Medicinal herbs have been in use for the management of human health, for prevention. as well as for the cure of human diseases since ancient civilizations. In recent times, the use of herbal drugs has increased in both developed and developing countries, because of the large chemical, pharmacological, and clinical knowledge of plant drugs and their derivatives, the development of new analytical methods for quality control, the development of new forms of preparation and administration of plant drugs and their derivatives and finally the relatively wide therapeutic margins with less frequent adverse effects. However, naturals are not a synonym for innocuous as many adverse effects can occur. In this regard, there are different levels of perceptions about the safety of medicinal herbs, varying from “completely safe” to “completely harmful”, although there is also a clear idea about its side effects depending on factors such as dosage, characteristics of the plant material and consumer-related factors. Because of this, medicinal plants need to be studied and effective and innocuous doses must be established. Nowadays, immunomodulatory drugs have gained a main role principally as a consequence of COVID-19 produced by the SARS-CoV-2 virus. Some South American plants frequently used in Argentine folk medicine such as Larrea divaricata and Ilex paraguariensis and others used all over the world like Tilia spp. and Coffeea Arabica are known to exert immune-enhancing effects. In this review, we discussed some reports about the immunological effect of the mentioned plants and their majority compounds, focusing on their efficacy and safety.

Management of Children with Systemic Diseases

Significant oral problems are associated with many medical disorders. Close cooperation and consultation between the dentist and the child’s physician are essential to render optimum medical care. Prevention of oral disease is the primary consideration for these children. Medically compromised children can be challenging to treat and affect dental care [30]. To treat medically compromised patients safely, it is essential to Obtain a relevant and thorough medical history and understand the possible implications of the illness on dental treatment and the potential importance of the condition on treatment planning and the caries risk associated with the medical condition. With advances in medical treatment, significantly more children survive longer with more complex medical needs, and these children will present to the general dentist for dental treatment.

Chromosome X

X Chromosome is the sex chromosome that is found in many organisms. Both males and females, including mammalians, have X Chromosomes. Females have XX sets of chromosomes, and males have XY sets of chromosomes. X Chromosome aids in identifying the sex of the organism. The Human X chromosome contains approximately 1500 genes. These genes may undergo some genetic alterations and eventually lead to complex diseases. Genetic mutations in some of the genes of the X chromosome are associated with cancer. Some specific mutations are observed in human cancer cells. This chapter specifically relayed on X chromosomal genes that are associated with different types of cancer and gave information on the location of the gene in the X chromosome. Moreover, the function of the specific gene and information regarding how many types of cancers were associated with a particular gene, has also been provided.

Biological Significance of Steroids

Steroids display varied biological functions and play a crucial role in the fascinating fields of biology, chemistry, and medicine.Steroids encompass wideranging natural products which are abundantly encountered in eukaryotic organisms. These exhibit a pivotal role in regulating the cellular functions of animals, plants, and fungi. Furthermore, they act as chemical messengers in the human body and get secreted in the systemic circulation and extracellular fluids, where they regulate metabolic, immune, and reproductive functions. Steroids are the fundamental components of cell membranes and serve primarily as signalling molecules. This chapter gives a comprehensive overview of physiologically active steroids in various organisms.The biological activities of various steroid classes have been discussed in detail. Glucocorticoids are a class of steroid hormones that regulate the metabolic processes involving the formation of glucose from amino acids and fatty acid deposition of glycogen in the liver. Another important group of hormones, called mineralocorticoids, helps in balancing water and electrolyte content in the body and primarily affects the kidney. The principal class of steroids viz. the sex hormones are essentially crucial for the development and maintenance of reproductive function and cause stimulation of secondary sexual characteristics in humans. To summarize, steroids stabilize and regulate the structure and functions of cellular membranes and play a crucial role in regulating growth and development.

Lipidomics Techniques and their Application for Food Nutrition and Health

Due to the chemical complexity and wide concentration range of lipids in biological samples, it is necessary to apply different analytical strategies to identify and quantify lipid species and amounts. In this book chapter, we mainly introduced the techniques, workflow, and applications of lipidomics in food nutrition and health. First, we mainly introduced the common lipidomics techniques, such as direct infusion mass spectrometry-based techniques, chromatographic separation mass spectrometry-based techniques, mass spectrometry imaging, and nuclear magnetic resonance. Second, we described the common lipidomics workflow, including sample preparation, MS data acquisition, and data processing. Third, we mainly discussed the application of lipidomics in food nutrition and health. Finally, we briefly summarized and discussed the future perspectives of lipidomics. All these discussions suggested that lipidomics could ensure food quality, examine dietary lipid nutrition, and prevent and detect diseases.

Abnormalities of the Central Nervous System

Psychological Distress and Consequences of COVID-19 Pandemic on Different Groups

The novel coronavirus 2019 (COVID-19) is extensively spreading all over the world, causing unprecedented hazards to mental health globally. The global pandemic of COVID-19 has been strongly impacting humanity and continues to influence all segments of the population since its origin. While dealing with such a public health crisis, past experiences have witnessed generalised public fear and anxieties due to uncertainty, causality and lack of public health preparedness. Therefore, it is important to acknowledge the detrimental effect of COVID-19 on the mental health of individuals of different age groups. This chapter aims to explore the impact of this unprecedented atmosphere on the mental health of the elderly, healthcare workers, children, adolescents and young people, pre-existing mental health conditions, post COVID-19 patients, women, homeless people and refugees. The chapter presents the direct and indirect psychological impact of COVID-19 on the genera at the individual, societal and public health levels. It will discuss at length some emerging concepts of the causal routes of mental disorders and suggest some strategies to prevent and promote mental health problems in individuals during this crisis. For the general population at large, just like physical effects, it is important to address the impact of COVID-19 on mental health effects as well. Various studies reported that mental problems such as anxiety, depression and fear of getting infected were common among people of all age groups who responded to COVID-19. The important lessons to be learned so far can help to devise individual mental health recommendations, as well as improved interventions and preventions of public health approaches.

Drugs For Relapse Prevention in Addiction: Review of Psychological and Neurological Factors, Genetics and Neurobiological Mechanisms

Behavioral and substance addictions share more similarities than differences in etiological, phenomenological, and clinical presentations. Interactions between the variables of predisposing (i.e., neurobiological and psychological constitutions) and moderating (i.e., coping style and cognitive and attentional biases), as well as variables of mediating (i.e., affective and cognitive reactions to situational triggers) in combination with reduced inhibitory control may accelerate or reduce the developing of specific versions of model for addictive behaviors. Around 50% individuals’ variability in becoming addicted to substance (nicotine, alcohol, or illicit drugs) is attributable to genetic factors. Genetic variations to addiction susceptibility and environmental factors such as stress or social defeat also alter brain-reward mechanisms impart vulnerability to addiction. The emergence and maintenance of addiction might be the consequences of chronic exposure to drugs remodeling the chromatin structure including FosB, Cdk5, G9a, and BDNF around genes. Only few drugs for substance use disorders (SUDs) are approved by the FDA, But QSP approaches provide valuable strategies for designing novel prevention or treatment towards drug addiction. Conjugate vaccines and monoclonal antibodies treatments generating high-affinity anti-drug IgG antibodies neutralizing drug doses in the serum might lead the immunotherapy for SUDs in the future.

Malaria

The World Health Organization (WHO) defines cerebral malaria (CM) as an otherwise unexplained coma in a patient with asexual forms of malaria parasites on the peripheral blood smear. Malaria is a severe, devastating illness characterised by respiratory distress, severe anemia, and cerebral malaria (CM). Altered consciousness, convulsions, ataxia, hemiparesis, and other neurologic and psychiatric impairments are noted in cerebral malaria. Thus, cerebral malaria is defined as a condition in which a human has Plasmodium falciparum, a parasite in peripheral blood, followed by neurological complications of any degree. CM accounts for 300,000 deaths per year, and almost any survivors there display severe neurological manifestations. Coma is the outcome of CM, which is again due to brain hypoxia due to inflammation, edema, Brain swelling, and vascular blockage, are all due to the sequestration of pRBCs in brain microvasculature [1, 2]. In Ugandan children with CM infected with P.falciparum, severe cognitive impairment, behaviour problems such as hyperactivity, inattentiveness, aggressive behaviour, loss of speech, hearing loss, blindness, and epilepsy were noted (Irdo et al. , 2010). Heme offered protective responses to ECM, by dampening the activation of microglia, astrocytes, and expression of IP10, TNFa, and IFNg [3].

Cancer Surveillance

Surveillance against tumors is governed by both intrinsic (non-immune) and extrinsic (immune) surveillance. While research on non-immune surveillance started as early as the 1960s when it was demonstrated that cell environment within and around can induce tumor-suppressing mechanisms, a major part of the progress is missing compared to immune surveillance. Part of the reason could be due to the fact that immune surveillance is seen to have more potential in therapeutic application in curing cancerous tumors compared to non-immune surveillance mechanisms. Many of the non-immune mechanisms are still under investigation as theories, although a few studies have shown their possibility. Contrary to this, there is a plethora of studies on immune surveillance. The immune system has been proven to have a role in the surveillance against tumors, thus conferring a certain degree of protection. However, not all tumor cells are successfully detected by innate immunity, and many of them have developed strategic ways of escaping adaptive immunity. The immunosurveillance in both animal models and humans shows overwhelmingly that cells with immunodeficiencies are more susceptible to tumor development. However, it is confounding that even immune-competent individuals develop tumors, and thus a significant process is responsible. Thus, immunoediting was proposed as a theory to explain why tumors can escape immunosurveillance. This chapter provides detailed evidence from animal and human tumors and analyses the mechanisms, pathways, and components implicated in tumor immune surveillance. The findings suggest that while immune surveillance could be the key to promoting immune function against the development of tumors, there is more research and understanding needed in the various mechanisms and cells implicated. This is because most, if not all, of the therapeutic studies using immune effectors have proved to be poor in preventing, treating, or regulating the development of tumors.

Exploration of Repurposed and Adjuvant Drugs in COVID-19 Patients, as well as Challenges and Ethical Issues Related to Drug Repurposing

The Coronavirus Disease (COVID-19), also referred to as Novel Coronavirus Disease, is a contagious viral disease with a high rate of confirmed cases. Therefore, treatment options are urgently needed to fight the deadly virus. Since there is no standard treatment available, it results in increased morbidity and mortality. The development process of a new drug takes years, so it is crucial to focus on repurposed drugs to reduce the severity of this disease. This review aims to describe the regulatory and molecular aspects of repurposed and adjuvant drugs for COVID-19 based on registered clinical trials and online literature. The use of repurposed drugs brings its own ethical issues and challenges. The challenges of the correct interpretation of existing pre-clinical/clinical evidence and the generation of new evidence concerning drug repurposing in COVID-19 and the issues faced by the repurposing community will also be discussed in the review. When drug repurposing is employed in emergency situations, regional limitations of clinical research ethics, involuntary risk burden, regulatory aspects and ethical issues, fairness in resource distribution for repurposed drugs become an issue that requires careful ethical consideration.

Repurposing Drugs: A New Paradigm and Hopes for Life-threatening Diseases

The process of repurposing drugs is an alternative to the conventional drug discovery process. It is a cost-effective and time-efficient process with high returns and low risk that utilizes mechanistic information of the existing drugs to investigate their novel applications against other disease conditions. The most significant benefit of drug repositioning is that it brings new life against novel/ orphan/ resistant diseases and pandemic outbreaks like COVID-19. As a result, widespread use of the drug repurposing strategy will not only aid in the more efficient fight against pandemics but will also combat life-threatening diseases. Therefore, repurposing drugs can provide a quick response to these unpredictable situations. In this chapter, we have tried to focus on various drug-repurposing strategies along with therapeutics for repurposing drugs against life-threatening diseases wherein little or no treatment is readily available.

Taurine and the Liver: A Focus on Mitochondria-related Liver Disease

Although the liver is the leading site for taurine (TAU) synthesis, the level of this amino acid in hepatic tissue is relatively low. It is well-known that TAU is efficiently redistributed from hepatocytes to the circulation. However, the human body’s capacity for TAU synthesis is negligible, and we receive a very high percentage of our body TAU from exogenous sources. Plasma TAU is taken up by several tissues, such as the skeletal muscle and the heart. The roles of TAU in liver function are the subject of many investigations. It has been found that TAU could have beneficial effects against xenobiotics-induced liver injury, alcoholism-associated hepatic damage, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or even viral hepatitis infections. The inhibition of cytochrome P450, alleviation of oxidative stress, inhibition of inflammatory reactions, and the mitigation of tissue fibrosis are fundamental mechanisms proposed for the hepatoprotective properties of TAU. On the other hand, many studies indicate that hepatocytes’ mitochondria are essential targets for the cytoprotective properties of TAU. The current chapter reviews the beneficial role of TAU on the most common liver disorders, focusing on the effects of this amino acid on mitochondrial function and energy metabolism.

Applications of Taurine in the Central Nervous System Disorders Linked with Mitochondrial Impairment

Taurine (TAU) reaches a high concentration in the central nervous system (CNS). The physiological role of TAU in the CNS is the subject of many investigations. It has been suggested that this amino acid could act as a membrane stabilizer, a modulator of calcium signaling, a trophic factor for neuronal development, and even be proposed as a neurotransmitter in the CNS. Besides, several investigations revealed the neuroprotective properties of TAU in various experimental models. Multiple mechanisms, including the inhibition of the excitotoxic response, the blockade of cytoplasmic calcium overload, regulation of oxidative stress, and the positive effects of TAU on mitochondrial parameters, have been proposed for the neuroprotective properties of this amino acid. Today, it is well-known that mitochondrial function and energy metabolism play a pivotal role in the pathogenesis of various neurodegenerative disorders and xenobiotics-induced neurotoxicity. Hence, targeting mitochondria with safe and clinically applicable agents is a viable therapeutic option in various neurodegenerative disorders. In the current chapter, the effects of TAU on the CNS will be highlighted, focusing on the positive effects of this amino acid on mitochondrial parameters. The data could help the development of safe therapeutic agents against CNS complications.

Subject Index

Practice of Sleep Medicine in Lithuania

Lithuania is a small country with a relatively short (31 year) history of independence in the modern era. Complicated history and geopolitical situation determined gaps in many socioeconomic spheres compared to other western European countries 30 years ago. Nevertheless, the country's ambitious goals and direction towards democratic values resulted in high recent socioeconomic ratings and acknowledgment among other European Union, NATO and Organisation for Economic Co-operation and Development members. The chapter presents short Lithuania’s geopolitical and healthcare system data, the current practice of sleep medicine, the practitioners involved, the availability of diagnostic tools and medications to treat common sleep disorders. It discusses challenges to the practice of sleep medicine: patient access to care, resource limitations and financial hardships, clinical and research knowledge gaps.

Sleep Medicine in Iceland – The Challenges of a Subarctic Small Nation

The practice of sleep medicine within Iceland has been shaped by its position as a sub-arctic Nordic nation with a small population and a strong tradition of sleep research.

The major facility providing clinical diagnostic and therapeutic sleep services is the Landspitali - The National University Hospital of Iceland. Sleep studies are mainly conducted as home sleep apnoea testing with video hook-up instructions and electronic questionnaires. In the context of the COVID-19 pandemic, the majority of positive airway pressure therapy initiation took place at the home of the patient with auto settings and remote follow-up.

Sleep medicine service challenges include inferior access for rural areas, funding limitations, the COVID-19 pandemic and low sleep education at a national level for both the general population and specifically healthcare staff.

The unique clinical and research knowledge gap of Iceland requires studies on the health effects of living at such a northern latitude. The high hypnotic and antidepressant use of Icelanders as well as the high prevalence of restless legs syndrome symptoms may be at least in part contributed by latitude. The 1-1.5 hour discrepancy between the solar clock and the local clock may also cause social jet lag in Icelanders but this needs to be studied further. Finally, social factors such as the high energy drink consumption of Icelandic teenagers and the high screen time made possible by the 99% internet penetration and a mobile connection percentage that exceeds the total population level may contribute to the short sleep length found in Icelandic teenagers.

Practice of Sleep Medicine in the United Kingdom (UK)

The practice of sleep medicine in the UK has made considerable progress over the past 3 decades. This has been driven by the invention of CPAP and the development of OSA services, but other factors related to National Health Service innovations and healthcare professional developments have also been important. Key challenges remain in service provision, education and research, and in resolving regional equalities in access to care.

Sleep Medicine and Surgery in Egypt: Evolution, Clinical Practice, Education and Research Services

All through Egyptian history, starting from the pharaohs, passing by the Coptic and Islamic eras up to modern Egypt, there have been different interests in healthy sleep and sleep hygiene. Myths about sleep medicine are common among cultures and in Egypt, lack of public awareness about sleep disorders makes most patients undiagnosed or ignorant about whom to consult about their symptoms. In this chapter, we aim to provide the reader with the current state of the art of sleep medicine in Egypt. We conducted a literature review, furthermore the opinion of sleep experts in Egypt was collected and stated in detail, and additionally Egyptian sleep centers were invited to answer a survey in order to collect information about the equipment and trained personnel presented in this chapter. There are three types of Egyptian medical education streams including, the public, private and Al-Azhar medical schools, in which undergraduate and postgraduate medical students can join and earn their degrees but there are no specialized degrees in sleep medicine yet, exact details about medical education in Egypt are provided below. Egypt has numerous health care system providers or sectors: public, private and financing agents’ parastatal providers. Nevertheless, sleep studies remain expensive for the Egyptian public and most insurance companies do not fund it, which makes the expenses of polysomnography the duty of the patient to pay from his own pocket. Egyptian sleep laboratories are governmental and private labs, the governmental labs usually exist in university hospitals, financial and educational hassles make accreditation of these labs by AASM difficult. We provided statistics describing these labs and the type of equipment they use. We tried to discuss the clinical and research sleep status in Egypt, additionally, we tried to suggest solutions for these challenging issues.

Sleep Disorders in Syria

Although there is no data on the prevalence of sleep disorders in the Syrian population, extrapolating from neighboring countries like Lebanon, Jordan, Iraq, and other Arab and Mediterranean countries, sleep disorders including sleep-disordered breathing are common. Non-Communicable diseases account for two-thirds of deaths. Hypertension, obesity, diabetes, and tobacco smoking are among the highest in the region. There is a strong association between NCDs and sleep-disordered breathing. Most sleep disorders in Syria are undiagnosed and untreated due to the absence of or very low access to sleep specialists and sleep testing, the absence of national policies, and low awareness within the medical community and among the public. The long conflict in Syria, which began in 2011, has resulted in a complex humanitarian emergency, with 6.7 million internally displaced people and 6.5 million refugees out of a total estimated population of 22.5 million. The conflict and the resultant destruction of the health infrastructure have led to a severe public health crisis, which has further impacted the health of the population. There is low access to sleep education, testing, and treatment, mostly in major urban centers, although the demands are increasing. There are ample opportunities to improve the practice of sleep medicine, in spite of the long conflict and war, if local champions, NGOs, national authorities, and medical societies adopted already-available resources, guidelines, and regulations, incorporated creative means and telehealth, and followed the recommendations of the World Health Organization on Sleep and Health.

Sleep Medicine in Iran: Current Practice, Challenges, and Future Direction

The Iranian Sleep Medicine (ISM) Society, established in 2005, has worked to increase public knowledge of how important sleep is to maintain health in the community and safety on the roads. The ISM has also had a strong role in the implementation of sleep tests and laboratory standards in collaboration with the Ministry of Health, training sleep specialists to diagnose and treat sleep disorders, certifying sleep labs to ISM standards, and conducting much needed research to improve sleep amongst Iranians. In this chapter, we will first introduce the current healthcare system highlighting the practice of sleep medicine in Iran. Next, we identify three challenges in delivering sleep medicine to millions of Iranians with potential solutions. The challenges are: (1) a limited number of trained sleep medicine specialists unequally distributed across all districts; (2) a limited number of certified sleep labs; (3) the need for insurance to pay for the diagnosis and treatment of sleep disorders such as obstructive sleep apnea, narcolepsy, and insomnia. Lastly, we present future directions for Iranian sleep research including much needed population-based studies to assess the prevalence of sleep disorders. While much progress has been made since 2005 to improve sleep health in Iran, we still have much work to do to reach our goal of significantly reducing disparities and promoting sleep medicine all over Iran toward a healthier future.

Past, Present, and Future Directions of Sleep Medicine in Thailand

Sleep Medicine is a growing discipline in Thailand. The formal 2-year-sleep medicine fellowship was approved by medical council of Thailand and established under four specialties including internal medicine, psychiatry, pediatrics, and otolaryngology in 2018. Thailand has also established formal sleep technologist courses and certification examinations since 2010. Sleep Society of Thailand was established in 2009 and subsequently other sleep societies were also established. All societies contributed to the development and advancement of sleep medicine in Thailand including the development of national clinical practice guidelines. There are limited numbers of sleep laboratories in the country particularly in government settings. Fortunately, polysomnography conducted at a sleep laboratory in a government hospital is covered by most of the health care coverage programs. However, CPAP cost is only covered by the civil service welfare system, limited private health insurance, certain state enterprise or government employees. There has been an increasing number of research in the field of sleep medicine in recent years. However, multicenter, multidisciplinary, longitudinal studies in the field of sleep medicine are still lacking. Internationalization in terms of hosting international conferences and awards by the international sleep society has increased the visibility of Thailand regionally and globally. Collaboration among various disciplines is the key to advancing the field forward.

Sleep Medicine in China

As the world's most populous country, China has a high prevalence of sleep disorders, posing a huge public health burden. After 30 years of development, more and more professionals, patients, and public health policymakers are recognizing the importance of sleep. Although sleep problem is recognized in the Traditional Chinese Medicine area, modern sleep medicine starts from the diagnosis and treatment of obstructive sleep apnea. By 2017, about 2,000 sleep centers had been established nationwide which can diagnose and treat OSA, narcolepsy, restless legs syndrome, REM sleep disorder, and other sleep diseases. Research in different sleep fields has emerged in the recent 20 years. However, there are gaps between the sleep service capacity and the demand from patients due to the lack of sleep professionals as well as the medical insurance coverage. Education and training of both physicians and technicians still have a long way to go. Understanding the development and challenges will help us maintain the development of sleep medicine in China.

Sleep Medicine in the United Arab Emirates

Sleep disorders are increasingly being recognized as a major health problem in the UAE. The rising prevalence, potentially modifiable risk factors, and impact on global health outcomes have prompted the growth of sleep medicine. The burden of under-recognized disease has encouraged patient and physician-centric education. Supported by nationalized health insurance plans, the medical fraternity has adopted a multi-disciplinary approach to optimize resources and outcomes, while recognizing that these measures are initial steps in the unique challenges posed.

Sleep Medicine in Canada

Canada has an expansive, challenging geography with diverse demographics. The country is an industrialized and democratic nation situated at the northern end of the Americas. Canada provides universal healthcare to all residents through a singlepayer system administered by its provinces and territories. Data suggests common sleep disorders are present at similar rates in other industrialized nations, with the exception of a larger number of shift workers and arctic residents subject to circadian disruption. Canada has ‘punched above its weight’ in contributing to the field of sleep medicine, with numerous well-known pioneering specialists in areas ranging from pathophysiology and diagnostic development, to pharmacologic, therapeutic and device treatment. The practice of sleep medicine is provided by trained physicians in neurology, respirology, psychiatry, internal medicine, family practice, otolaryngology, pediatrics, as well as psychology and dentistry amongst other providers. Major challenges to Canadian sleep medicine include limited public healthcare funding, variable funding mechanisms across the nation’s jurisdictions, limited access to diagnostic and therapeutics, and conflicts-of-interest with business. Certain demographic groups are particularly at-risk, including socioeconomically challenged communities, indigenous populations, and other diverse minority groups. Canada’s characteristics and challenges provide it with substantial research opportunities and a chance to lead in such areas as epidemiology, sleep medicine genetics, ethnic and cultural aspects, circadian and shift work considerations, home polysomnography and post-COVID transitions to more virtual sleep medicine care.

Current Practice of Sleep Medicine in the USA

Sleep medicine and its practice in the United States of America (USA) has grown from the first center focusing on sleep disorders established at Stanford University in 1964 to more than 2,500 American Academy of Sleep Medicine (AASM) accredited sleep centers and numerous professional organizations supporting sleep health professionals including board-certified sleep medicine physicians, behavioral sleep specialists, advance practice registered nurses and/or physician assistants and sleep technologists. As sleep medicine continues to grow in the USA, multiple challenges including widening economic inequality, racial/ethnic inequities, and limited healthcare access directly affects the patient setting. Limited sleep medicine education in medical school restricts the ability to educate patients as well as primary care providers on the importance of identifying sleep disorders early on to improve access. The financial burdens of diagnosing and treating sleep disorders, particularly obstructive sleep apnea is seen in an estimated cost of $16 billion annually. Research and data collection includes surveillance surveys conducted by the Sleep and Sleep Disorders Team from the Centers for Disease Control and Prevention (CDC) as well as continuing research in the diagnosis and treatment of obstructive sleep apnea. Additional studies addressing sleep issues and racial disparities in the US are prudent in highlighting this crucial area. Continued efforts in clinical and research knowledge gaps are necessary to support the growing need for sleep medicine providers and services in the USA.

Advent of Pharmabiotics as a Promising Therapeutic Tool for Human Health and Diseases Management

With the recent advances in understanding the role of the gut microbiome and human health, it has become evident that pharmabiotics have huge potential in the therapeutics as well as supplement industries for conditions leading to impaired microbiota. Pharmabiotics can be referred to as a class of microbial therapeutic probiotics which could be live bacterial cells of human origin or their products with clinically proven pharmacological activities found to be beneficial in human disease conditions. So, the mechanism by which bacteria produce synergistic beneficial effects on health could help us to develop a scheme to understand the delicate relationship between the gut microbiome and human health. In this chapter, we will emphasize the role of gut microbiota, the pharmabiotics they produce and how it affects different physiological and metabolic and host-microbe interactions leading to the production of bioactive chemicals with health benefits, eventually leading to the establishment of a healthy immune system. The chapter will also discuss the repercussions of disturbed gut microbiota on overall human health, including host psychiatric health. The fact that pharmabiotics acting as antimicrobial agents will produce no resistant variety is also an added bonus that increases the scope for discovery of such novel therapeutic agents.

Subject Index

Analgesia after Labor and Cesarean Section: Chronic Pain after Pregnancy

Chronic pain (CP) conditions after childbirth include persistent pain after caesarean section (CPCS), perineal pain after instrumental vaginal delivery, lower back pain and pelvic girdle pain. Any type of CP before or during pregnancy increases the risk of CP after delivery. Scar pain is the most recognized etiology for CPCS with a neuropathic component, although it is less frequent than in other surgeries. Reported CPCS incidence ranges from 1 to 23%. Pain intensity is moderate and decreases with time in all studies. The severity and duration of peripartum pain are the main risk factors for CP and its control is the most recommended strategy for reducing risk. Fear of fetal and neonatal adverse events means that CP is often undertreated, but after delivery, pharmacological restrictions disappear and many pain drugs are compatible with breastfeeding. Education of obstetric teams about early detection and referral to specialized consultation of women with CP is the key. In this chapter, available information in the recent literature, mainly during the last years, is presented. This chapter focuses on CP conditions after childbirth, as analgesia for labor and childbirth and immediate pain after CS and vaginal delivery are covered in other chapters of this book.

Air and Amniotic Fluid Embolism

Amniotic fluid embolism (AFE) is an uncommon pathology, whose incidence ranges from 2 to 8 per 100,000 births, depending on the country. This syndrome has four cardinal symptoms: circulatory collapse, respiratory distress, cyanosis and coma. If the patient survives cardiorespiratory failure, disseminated intravascular coagulopathy occurs, leading to incoercible bleeding and eventually death. Clinical diagnosis is based on Clark's four criteria: sudden cardiorespiratory arrest, established disseminated intravascular coagulation prior to bleeding, and all of these occurring peripartum in the absence of fever. The two main differential diagnosis syndromes are pulmonary thromboembolism and myocardial infarction. Treatment consists of cardiopulmonary support of the patient. Despite aggressive measures, such as the placement of ventricular assist devices and external oxygenation membranes, the prognosis continues to be poor. The main death cause is incoercible bleeding caused by disseminated intravascular coagulopathy.

Anesthetic Management of the Pregnant Patient with Comorbidities

An increase in pregnant patients with comorbidities has been seen in the last decade. Nevertheless, these patients are able to enjoy longer and better quality lives nowadays. During pregnancy, patients can experience decompensations of their chronic disease which can be sometimes challenging for the medical team. Complexity has risen; that is why the anesthesiologist must be updated and capable of facing different scenarios both in the delivery room and before or after birth. This chapter offers a practical and synthetical approach to the most common situations in which a general anesthesiologist can be involved, aiming to emphasize main points for safe and accurate anesthetic care.

Modulation of Proinflammatory Cytokines by Flavonoids in the Main Age-related Neurodegenerative Diseases

Aging is a process associated with distinctive changes in physiological functions and physical appearance that result from progressive tissue degeneration, harming the structure and function of vital organs. Illnesses that are particularly frequent in people 65 years of age and older are generally grouped as age-related diseases or aging-related diseases and include neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), which are caused by progressive degeneration and/or neuronal death to produce debilitating conditions, and they have no cure. For these illnesses, the most important risk factor is aging. Aging involves changes in neuroendocrine and inflammatory responses and presents a stage with chronic and low-grade inflammation, characterized by a general increase in the production of proinflammatory cytokines, inflammatory markers, and cellular senescence. Herbal medicine, as well as various components of the human diet, including vegetables, cereals, and fruits, contain widely varied phytochemicals including flavonoids, which are the most common polyphenolic compounds. Epidemiological studies suggest that a higher intake of flavonoid-rich foods and beverages is associated with better cognitive outcomes, lower dementia rates, and reduced risk of neurodegenerative diseases. Moreover, numerous preclinical studies have shown that these compounds have a therapeutic effect on animal models of human degenerative diseases and highlight the anti-inflammatory effect of flavonoids by decreasing the activated glial cells and several proinflammatory mediators. Much modern scientific research has focused on establishing biological activities of purified single compounds to provide an evidence base for the rationale of traditional practice, and also to integrate these into modern medical practice.

Subject Index

COVID-19: Sign, Symptoms and Transmission

COVID-19, which is caused by SARS-CoV-2, was first reported in Wuhan, China in late 2019. Till date, over 12.1 million people have contracted the disease across 221 countries in the world. The global fatality rate is about 6.2% thus far, and as of May 26th 2020, the highest confirmed cases were recorded in the USA, Brazil, Russia, Spain, UK, Italy and France. Several attempts to fight against the virus are taken by the World Health Organization (WHO) as well as other health agencies in various countries with reported confirmed cases. The present study has reviewed COVID-19 with respect to the clinical symptoms and signs, as well as factors that could exacerbate COVID-19 condition and transmission amongst people. Recent reports and studies have found the disease status to be of the predominantly mild condition and to a lesser extent, a critical/severe status. COVID-19 presents several clinical manifestations with symptoms such as fever, dry cough, fatigue, dizziness, anorexia, headache, expectoration, dyspnea, chest tightness, abdominal pain, diarrhea and nausea. Studies have observed age, obesity, smoking and drinking habit, immune system condition, human selectivity and reactivity as factors that can aggravate the disease condition, while poverty, fake news, non-validated scientific claims, and perception/illiteracy have been reported as risk components that could enhance the transmission of the viral infection. This study concludes by suggesting the appropriate methods to combat the factors discussed.

Rho/Rho Kinase Signaling Pathway and Disease: from Bed to Bench

Since Madaule and Axel first discovered Rho gene in 1985, Rho and its signal transduction pathway have been extensively studied. Rho protein family belongs to the small GTP binding protein of Ras super-family, whose molecular weight is between 20kd-30kd. As a molecular switch, Rho protein family controls many signal transduction pathways in eukaryotic cells. There are two states of Rho protein, one is the inactivation state bound to GDP (GDP Rho), the other is the activation state bound to GTP (GTP Rho). In the resting state, the GDP Rho dissociation inhibitor (rho GDI) is bound to the GDP Rho and located in the cytoplasm. GTP was substituted for GDP to activate Rho protein by guanosine exchange factor (GEFs). GTP Rho interacts with the downstream effector Rho kinase (ROCK). There are two types of ROCK: ROCK1 and ROCK2. The activation of ROCK can inhibit the activity of myosin phosphorylated light chain phosphatase (MYPT1), thus increasing the level of myosin phosphorylated light chain (MLC) in cells, leading to increased sensitivity of vascular smooth muscle cells to Ca2+ and vasoconstriction. Previous studies have shown that Rho/ROCK signaling pathway not only plays an important role in vasoconstriction, but also regulates cell movement, proliferation, adhesion, activation of cytokines and migration of inflammatory cells. At the molecular level, the expression of ROCK upregulates various factors that promote oxidative stress, inflammation, thrombosis and fibrosis, and down-regulates endothelial nitric oxide synthetase. At the cellular level, it is involved in many cell functions such as gene expression, cytokinesis, cell adhesion and migration. It has been found that Rho/Rho kinase is related to cardiovascular diseases, such as coronary atherosclerotic heart disease, hypertension, heart failure and so on. Fasudil, a potent and selective inhibitor of ROCK, can treat many cardiovascular diseases and has been used in clinical practice. This article reviews the relationship between Rho/Rho kinase and many system diseases.

Subject Index

Nutraceuticals: The Potential Agents to Rescue Human Race from Cardiovascular Diseases (CVDs)

Cardiovascular disease(CVD) is the foremost global health problem that accounts for the highest rate of morbidity, mortality and huge healthcare costs. Food habits and lifestyles predominantly affect the functioning of the cardiovascular system either directly or indirectly through risk factors like hypertension, obesity, dyslipidemia, diabetes, etc. Decreased physical activity, increased sedentariness, and growing fast food culture are some of the apparent reasons that make the disease impact more on the younger generation. Several plant species have been reported in ethnomedicine for their therapeutic efficacies against CVDs and other diseases. Even though some preclinical and clinical studies have demonstrated the beneficial effects of dietary plant components in the prevention and treatment of CVDs, they are limited to selected study groups. Therefore, their scope and utility need to be broadened and applied to larger populations to reduce the public health burden of CVDs. Since nutraceutical approach is more preferable than other therapeutic methods, there is a growing interest in functional foods and diet based remedies. In the present chapter, we have presented the current scenario of CVDs, their pathophysiology, the therapeutic drugs available, the role of nutraceuticals in treating CVDs and their mode of action with a special emphasis on commonly used kitchen spices.

Subject Index

Metabolic Syndromes

Metabolic Syndromes (MetS) are recognized as a cluster of risk factors which are known to increase the likelihood of obesity, type 2 diabetes (T2D) and cardiovascular disorders (CVDs). It is significant to understand disease pathology in order to discover a pathological mechanism leading to the development of MetS. Elevated triglycerides, increased blood pressure, hyperglycemia (increased blood glucose levels), low levels of High-density lipoprotein (HDL) cholesterol and elevated waist circumference are key parameters in diagnosing MetS. Various therapeutic interventions have been developed for treating metabolic diseases like polypills which are commonly known as combination pills, along with the fixed dose combinations. In addition to pharmacological handling, surgical treatment is also showing success in treating MetS such as Bariatric treatment. With the emerging experimental techniques, gene therapy allows the replacement of a defective gene with a healthy one, which may eventually reverse the disease. Leptin Gene Therapy, ZFN Gene Editing, CRISPR/ Cas9 genome editing are different platforms of gene therapy which are showing promising results in treating the metabolic disease. Novel experimental approaches and pharmacological treatments can provide a better insight into metabolic syndrome and its related complications, thereby reducing its global burden.

Work-related Musculoskeletal Disorders

In most industrialized countries, work-related musculoskeletal disorders (WMSDs) are a major occupational health problem resulting in productivity loss, employee absenteeism, and high workers’ compensation and healthcare costs. Understanding the etiology and control of WMSDs and associated risk factors is imperative for reducing the burden of this problem. This chapter is organized by five topics on WMSDs: (1) the problem and surveillance of WMSDs; (2) the etiology of WMSDs and their risk factors; (3) risk assessment methods for job-related physical risk factors; (4) risk intervention effectiveness; and (5) ergonomic guidelines and standards for the prevention of WMSDs. The authors focus on the breadth of the scientific knowledge and literature pertaining to WMSDs for occupational safety and health professionals interested in learning about the field of ergonomics. This chapter also provides anticipated future challenges in the areas of surveillance, risk interactions, risk assessments, and intervention evaluations. The research agenda for WMSDs published by the National Occupational Research Agenda (NORA) Musculoskeletal Health Cross-Sector (MUS) Council in 2018 is recommended as supplementary reading for the future direction of WMSD research.

Subject Index

Cervical Endoscopic Unilateral Laminotomy for Bilateral Decompression (CE-ULBD) – A Technical Perspective

Cervical endoscopic unilateral laminotomy for bilateral decompression (CEULBD) is an applicable surgical method in cases of central canal stenosis, usually associated with myelopathy. Other authors have shown the feasibility, safety, and efficacy of this method. They could also demonstrate more favorable perioperative benchmark data of this procedure than anterior cervical discectomy and fusion (ACDF) in terms of duration of surgery, blood loss, and hospital stay. In this chapter, the authors focus on the technological advances making this surgery possible. Moreover, the authors review the relevant surgical anatomy to enable the aspiring endoscopic spine surgeon to safely and successfully perform the CE-ULBD procedure. Experience in advanced endoscopic surgery in other areas of the spine is recommended before imparting on the posterior endoscopic decompression of the stenotic central cervical spinal canal. The authors have implemented CE-ULBD in formalized and wellstructured Endoscopic Spine Academy (Espinea®) training programs, intending to provide high educational standards to achieve favorable outcomes with the CE-ULBD procedure reproducibly.

Subject Index

Clinical Application of Circulating MicroRNAs as Novel Biomarkers for Different Diseases

Biomarker research has become increasingly interesting in many areas nowadays. Biomarkers are indicators of the biological process that can show changes in disease and health status and reveal pathological conditions. There is always a need for markers that divide patients into risk categories that can help in early diagnosis, detect complications ahead of time, guide treatment, and predict adverse outcomes in a chronic complex and certain diseases such as cancer. microRNAs (miRNAs) are ~ 22 nt long npcRNAs involved in post-transcriptional arrangements. miRNAs regulate messenger RNAs (mRNA), especially through negative regulation of gene expression. The fact that miRNAs have come to the fore in many disease mechanisms brings up their use as biomarkers in the early stage. The purpose of this review is to gather the latest information on this subject by bringing together recent articles and reviews to contribute to understanding the role of miRNAs, which act as biomarkers in different ways in vital processes, in the formation, early diagnosis, and treatment of diseases. miRNAs have an important potential to become a next-generation biomarker and therapeutic. But, each miRNA molecule can bind to a large number of different mRNAs, and different miRNAs in each mRNA. Therefore, new findings are needed to determine the expression activities and targets of miRNAs.

A Pathophysiological Approach To Current Biomarkers

Biomarkers are necessary for screening and diagnosing numerous diseases, predicting the prognosis of patients, and following-up treatment and the course of the patient. Everyday new biomarkers are being used in clinics for these purposes. This section will discuss the physiological roles of the various current biomarkers in a healthy person and the pathophysiological mechanisms underlying the release of these biomarkers. This chapter aims to gain a new perspective for evaluating and interpreting the most current biomarkers.

Specific Diagnoses and Management Principles of the Upper Digestive Canal

Acute abdominal conditions which frequently necessitate emergency interventions and/or surgery include visceral perforations i.e., gastric and duodenal ulcer, bleeding and rarely, ingested foreign bodies causing tissue damage, e.g., button batteries. However, the differential diagnosis (DD) of patients presenting with acute abdominal pain is much broader than this, including many benign conditions as well. Acute gastroenteritis, acute gastritis and peptic ulcer disease are benign and mostly temporary diseases which may be relieved with simple treatments and follow-up. Gastrointestinal bleeding (with or without esophageal varices) may cause hemorrhagic shock unless expedient management is pursued. Ingested foreign bodies can constitute emergency conditions with tissue damage, especially when lodged in a specific site. The most important thing about button batteries is the prevention of their ingestion. Complications increase in direct proportion to time wasted.

The “Stomachache” of Medicine: Concepts and Mechanisms of Abdominal Pain

Abdominal pain (AP) is by far among the most common complaints in healthcare institutions. Approximately every tenth patient in the acute setting is estimated to present with AP. Although cultural, geographical and sociodemographic variations exist, it is an outstanding complaint in all patient groups, independent of age and gender. Although it can be a manifestation of an intraabdominal pathology itself, a serious systemic or extraabdominal condition can be revealed following a thorough investigation of AP. Therefore, it is vital to evaluate the patient systemically, a focused but elaborate history, and extensive physical examination not confined to the abdomen in order to establish important diagnoses. Inspection, auscultation, percussion, superficial and deep palpation are important elements of the examination methods for the abdomen. Each positive or negative finding on examination should be interpreted cautiously for the individual patient. After history and evaluation narrow the list of differential diagnoses (DD), ancillary investigations including laboratory tests and radiological modalities can be ordered.

Molecular Diagnostics and Immunological Markers of Neurodegenerative Disorders

Neurodegeneration is a progressive process that occurs with normal aging with accelerated loss of normal functioning and structure of neurons. The physiological aging of neurons can be expedited by many different factors like neurodegenerative diseases (NDs) including frontotemporal lobe degeneration (FTLD), Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), etc. In the clinical view, the symptoms of different types of neurological disorders have a high degree of similarity, making it difficult for differential diagnosis. Clinicians need strong expertise to reach a correct diagnosis for a particular disease as there are so many established clinical guidelines for the diagnosis of different types of neurological disorders. Here, in this chapter, we shall focus to understand the different molecular diagnostic tools and immunological markers used for the detection of neurodegenerative disorders.

Interrelationships of Phytochemicals, Micronutrients, Gut Microbiome and Health

Many plants and herbs have been known for healing a variety of health disorders since the ancient practice of medicine. Recent advances in laboratory methods have now identified the chemical compounds in plants (phytochemicals) that are responsible for the health-promoting effects. There are thousands of phytochemicals known so far which have no nutritional value but can help in many biological processes in the human body. The phytochemicals mainly include flavonoids, carotenoids, phenolic acids and lignans. They play a role in many body functions and are equally important as micronutrients in maintenance of health and wellbeing. The synergistic actions of phytochemicals and micronutrients as antioxidative and anti-inflammatory agents may contribute towards disease prevention and betterment of health. Food sources of phytochemicals, their role in various metabolic functions, and health effects are described in this chapter. Gut microbiome, which comprises of intestinal microbial population, performs important functions like digestion of food, regulation of immune system and shares an interactive relationship with dietary nutrients and non-nutrients. Phytochemicals that can influence the gut microbiome have recently been studied as adjuvants for the treatment of obesity, diabetes, cardiovascular disease and inflammatory diseases. The effect of different phytochemicals on gut microbiota and their beneficial health effects are elucidated. New developments related to potential of probiotics as prophylaxis or their therapeutic use in treating the COVID-19 infection is briefly mentioned.

Linkages Between Micronutrients and Health

Micronutrients perform a key role in almost all vital body functions like those related to vision, immunity, bone formation, brain function and many others that help in proper growth and maintaining good health. Deficiency of any one or more of the micronutrients can have a negative impact on the overall health. The causes of micronutrient deficiencies and their signs and symptoms are explained in this chapter in a precise manner. Plant and animal food sources with high micronutrient contents with ready-to-eat food supplements per serving size are illustrated for each micronutrient. These can serve as a guideline for preventive measures and diet therapy. Micronutrients are increasingly used as an adjunct therapy in managing various health problems. Effective therapeutic uses of vitamins and minerals are exemplified for a ready reference. Overdose of synthetic supplements of micronutrients and certain environmental conditions may result in toxic effects. To address this, the upper limit for micronutrient intakes and toxic effects of excess micronutrient intakes are also described. The relevance of the yogic concept of ‘sattvic’ diet in modern nutrition and the potential of yoga for micronutrient absorption is also highlighted. The approach of yoga towards healthy diet and the relation between diet and psychological health is explained based on experimental data. The importance of specific micronutrients in health at different stages of life, from pregnancy to old age, is elucidated and remedial measures are suggested. Lastly, evidence for micronutrient supplements as an adjunct therapy for COVID-19 is briefly described.

COVID-19: Clinical, Immunological, and Image Findings from Infection to Post-COVID Syndrome

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virus responsible for the COVID-19 pandemic outbreak. The virus has high infectious power and easy ability to spread geographically, due to the fact that the infection is asymptomatic in some cases. However, 25% of patients infected by SARS-CoV-2 can progress to the severity of the disease and develop acute respiratory distress syndrome (ARDS). The symptoms are commonly recognized as fever, dry cough, tachypnea, shortness of breath, sore throat, sneezing, nasal congestion, and other symptoms, including severe inflammatory responses with the evolution of cytokine storm, pneumonia, and sepsis. Here, we show the COVID-19 since infection in the host cell to Post-COVID-19 syndrome, relating the occurrence of virus variants, laboratory and immunological aspects, the major clinical manifestations and image findings, and all aspects associated with pulmonary damage promoted by the virus.

Physiological Basis for the Indication of Mechanical Ventilation

The respiratory system has a vital function in our body and several disorders

can cause Respiratory Insufficiency (RI). This disease, in turn, has an acute or chronic

form, as well as being classified as hypoxemic, hypercapnic and mixed. In addition,

there are three groups that cover the causes of RI, which are: hypoventilation,

impairment of diffusion and disturbances in the relationship between perfusion

ventilation. With regard to clinical manifestations, the respiratory system is affected by

this condition, from which the diagnosis of RI is made by blood gas analysis that

allows to differentiate it. In these cases, the patient is monitored by oximeters and

capnographs, the treatment being carried out by oxygen therapy and the use of invasive

and non-invasive mechanical ventilation.

Anesthesia for Uncommon Pediatric Diseases

Several uncommon pediatric diseases encountered by non-pediatric anesthesiologists bear discussion because a failure to recognize unique issues relating to them could lead to significant morbidity and mortality. Anterior mediastinal masses share the same space as major pulmonary and cardiovascular structures, which, if compressed, can compromise the airway, heart and great vessels. Awareness of the potential for major physiologic derangement and a multidisciplinary approach to their diagnosis and management will ensure a safe perioperative course. Congenital pulmonary airway malformation is one of the most frequent pulmonary malformations in children that requires surgical intervention by thoracoscopic approach in the first year of life. Their anesthetic management is often challenging due to their small size, need for lung isolation and maintaining adequate oxygenation during surgery. Understanding lung isolation technique in infants is necessary for the safe administration of anesthetics in these children. Arthrogryposis multiplex congenita syndrome is a rare, non-progressive, and congenital heterogeneous group of disorders characterized by congenital joint contractures. These children require frequent surgeries during childhood to address various musculoskeletal abnormalities. Their anesthetic management is often challenging due to comorbidities related to musculoskeletal deformities, neurologic, cardiovascular and respiratory systems involvement. Understanding the disease with thorough evaluation and preparation prior to anesthetic management is essential for a good perioperative outcome. Pheochromocytoma is a rare neuroendocrine tumor in children that may present unexpectedly for the management by anesthesiologists. It secretes catecholamines which can cause lifethreatening perioperative hemodynamic instability. The meticulous preoperative pharmacotherapy, intraoperative anesthetic management and postoperative monitoring are vital for a safe outcome.

Muscular Dystrophies and Mitochondrial Myopathies

Children with neuromuscular diseases have a broad range of presentation and anesthesia considerations. Muscle strength is reduced by degenerative nerve supply and affected neuromuscular junctions or by weakening of muscle fibers directly. Muscular dystrophies are an inherited group of disorders characterized by progressive muscle weakness. These children pose specific challenges related to anesthetic care due to skeletal muscle, pulmonary, and cardiac involvement. This chapter discusses the perioperative management of children with Duchenne, Becker, limb-girdle, EmeryDreifuss, and myotonic muscular dystrophies. Also discussed are mitochondrial myopathies, a group of clinical conditions common to the pediatric population. Cerebral palsy (CP) is a nonspecific, descriptive term that encompasses a constellation of symptoms due to a neurologic lesion resulting from the insult to the developing brain sustained early in life. Although the neurologic lesion in CP is non-progressive, the motor dysfunction due to spasticity may be progressive, leading to spinal deformities, joint contractures, and dislocations requiring medical and surgical interventions. Anesthetic care for children with the above stated neuromuscular disorders requires understanding of their disease process and careful attention to all aspects of perioperative care. Thoughtful planning should include thorough preoperative assessment, attention to co-morbidities, management of chronic medications, and meticulous intraoperative care for these patients. Postoperative assessment of pain and its management are essential to facilitate recovery and uneventful perioperative course.

Anesthetic Considerations for the Critically Ill Pediatric Patient

In comparison to adults, critical illness is relatively uncommon in the pediatric population. Many facilities may be unprepared or ill-equipped for treating these rare conditions. The conventional anesthesiologist may not be familiar with the common pathologies of critical illness in children. These patients may need complex and life-saving urgent procedures to stabilize them. It is logistically challenging to have pediatric trained personnel readily available at all hospitals and care centers. These patients have special perioperative needs that the anesthesiologist should consider. They may potentially present to the operating room, emergency department, or pediatric intensive care unit. Here, we offer a direct and practical approach to managing the care of these younger patients.

Anesthesia for Pediatric Patients with Common Comorbidities Part III

There have been dramatic improvements in the survival of neonates and children with many diseases and disorders due to advancements in medicine over the past several decades. These advances are attributed to the better understanding of these disease processes, the advent of multidrug combinations, molecularly targeted therapies, critical care and various surgical interventions. In the wake of this rapidly developing wide range of treatment protocols, the anesthesiologist needs to have a clear understanding of these disorders and their comorbidities, and stay abreast of the various treatment modalities, including their safety and toxicity profiles. This review attempts to emphasize some of the clinical conditions unique to these patients and special considerations for the conduct of anesthesia in this population. Some of the disease processes and comorbidities discussed here include anesthetic considerations for ex-premature infants, diabetes mellitus, obesity, childhood cancer, and children with congenital heart disease who present for non-cardiac surgery. The objective of this discussion is to provide an updated and comprehensive review of current perioperative anesthetic management of pediatric patients with these conditions. We also delineate the effects of anesthesia during the perioperative course, including major metabolic changes that may result in increased morbidity. We provide guidelines for any anesthesia provider involved in the care of these vulnerable patients. Special considerations need to be taken to promote the physical and mental wellbeing of these children and their families. Collaborative coordination with all providers involved in care is essential to provide safe and effective anesthesia to this subset of patients.

Anesthesia for Pediatric Patients with Common Comorbidities Part I

Children undergoing anesthesia have many considerations of disease processes that require careful attention to details and addressing specific needs. There are several comorbidities that are frequently encountered in a pediatric setting. A common scenario is a child with an upper respiratory tract infection presenting for elective surgery. We will discuss the criteria to be considered regarding when it is safe to proceed with elective surgery and when the risk is high. Asthma is common among children, and exacerbation can occur during an anesthetic. Anesthetic management of children with these respiratory illnesses is discussed. Children with Down syndrome frequently present for various cardiac and non-cardiac surgical interventions. Anesthetic issues relating to their non-cardiac surgeries will be discussed. Children with sickle cell disease is yet another group of patients frequently admitted to the hospital with sickle cell crisis. They warrant attention to specific details to ensure getting through surgery safely and require optimal pain management. Obstructive sleep apnea is increasingly encountered in children presenting for surgical procedures. Anesthetic challenges and risks they pose will be discussed.

Fenugreek (Trigonella foenum-graecum L.): A Palatable Spice, An Active Herb, A Promising Functional Food, and Even More

Since ancient times, Trigonella foenum-graecum (fenugreek), a plant from the legume family (Fabaceae), is one of the most popular spices worldwide. Medicinal benefits and properties of this plant have been recognized. Fenugreek has a long history as a remedy for diabetes mellitus with a known effective anti-diabetic plant. The studies indicated that T. foenum-graecum has several important biological activities, such as potent immunomodulation-associated anticancer and anti-inflammatory effects. Besides the healing properties, it is stated as a functional food for promoting well-being and a tasty spice often used in the kitchens and the industrial fields. However, to the best of our knowledge, no research has been done so far concerning this plant as a comprehensive literature search. In this chapter, we discuss how fenugreek may be beneficial in clinical and prophylactic health and what further research is necessary to understand whether regular consumption can contribute to healthy living generally

Introduction of Common Pediatric Diseases

Pediatric health has improved over the past decades and there is a decline in deaths caused by infectious diseases. Yet, the top three causes of disease in children younger than 10 years in 2019 include neonatal disorders, lower respiratory tract infections, and diarrheal diseases. While in the adolescence age group, the major causes are road injuries, headache disorders, and self-harm. Preterm birth complications, pneumonia, and birth asphyxia are the most leading cause of death in children under five years. While in the five to nine years of age group, injuries, including road traffic injuries, drowning, burns, and falls, are the leading causes of death.

Silver Sleepers: Sleep and Ageing

Sleep difficulties and disorders are among the most prevalent problems of ageing. In addition to changes in sleep duration and quality, sleep architecture also changes as age progresses. Age by itself does not result in sleep disorders; rather, these changes are associated with psychosocial and health factors in the elderly such as the existence of multiple comorbidities, polypharmacy, and age-related changes in circadian rhythm. Older adults have increased prevalence of various primary sleep disorders, including restless leg syndrome, insomnia, sleep-disordered breathing, circadian rhythm disturbances and periodic limb syndrome. Challenges in identifying, diagnosing, and treating sleep disorders in older adults with dementia also exist, which further complicates the management of sleep disorders in these patients. Poor sleep not only impacts the quality of life and cognitive functioning but is also associated with increased morbidity and mortality and thus requires careful screening and assessment in the elderly population.

REM Sleep Behavior Disorder: Diagnosis, Epidemiology & Management

REM Sleep Behavior Disorder (RBD), often known as injurious dream enacting behaviors secondary to loss of atonia in REM sleep, was first described in 1986. While in the younger population, RBD can be associated with narcolepsy, posttraumatic stress disorder (PTSD) and antidepressant use, in middle-aged and older adults, RBD is almost always associated with a neurodegenerative disorder of synuclein––primarily Parkinson’s disease and dementia with Lewy bodies. For this reason, so-called isolated, or idiopathic RBD (iRBD), is in the great majority of cases a prodromal manifestation of neurodegeneration. Diagnosis of RBD requires video polysomnography to rule out common mimics. Specific diagnostic procedures and thresholds of electromyography (EMG) activity for the diagnosis of RBD have been developed and show high accuracy. Epidemiological studies have placed the overall prevalence of RBD around 2% across all age groups. Sleep-related injurious behaviors are common in RBD, especially in men, explaining the higher proportion of males diagnosed with RBD. In the management of RBD, safety is therefore paramount. Prognostic counselling is often warranted in iRBD, given the high rate of conversion to overt synucleinopathy. Offending agents, such as serotonergic medications, should be reduced or discontinued as possible as they exacerbate RBD behaviors. Pharmacological management involves primarily melatonin and/or clonazepam, while transdermal rivastigmine and, in select cases, sodium oxybate may be considered in treatment-resistant cases.

Management of Non-Narcolepsy Hypersomnia and Excessive Daytime Sleepiness

The International Classification for Sleep Disorders- third edition (ICSD-3) has classified central disorders of hypersomnolence as, Narcolepsy type 1 and type 2, idiopathic hypersomnia (IH), Kleine–Levin syndrome (KLS), hypersomnia due to a medical or neurologic disorder, hypersomnia due to medication or substance, hypersomnia associated with psychiatric disorders, and insufficient sleep syndrome. A number of pharmacological treatment options are now available for Narcolepsy type 1 and type 2. However, for conditions like IH and KLS, much work is still being done to understand the underlying pathophysiologic mechanisms and consequently, these conditions have the least amount of high-grade evidence on pharmacologic options, and most medicines are used ‘off-label’. This chapter focuses on treating non narcoleptic hypersomnia syndromes- those commonly encountered in Sleep disorders clinics such as residual hypersomnia despite having a patient adherent to therapeutic positive airway pressure settings, to some uncommon conditions like IH and an exceedingly rare condition like KLS. New medications like solriamfetol and pitolisant and their possible use in some of these conditions is also discussed in this chapter

New Approaches in P2Y12 Receptor Blocker Drugs Use

Thienopyridine-derived clopidogrel, prasugrel, cyclopentyltriazole pyrimidine-derived ticagrelor, and non-thienopyridine-derived ATP analogue cangrelor block the P2Y12 component of ADP receptors on the platelet surface. This prevents activation of the GPIIb/IIIa receptor complex, thereby reduces platelet aggregation. The platelet activation pathway caused by ADP is blocked by P2Y12, and therefore, these drugs have a crucial role in preventing ischemic complications in patients undergoing acute coronary syndrome, including unstable angina, myocardial infarction, and percutaneous coronary intervention. In addition, the use of P2Y12 inhibitors for secondary prevention has also been focused on in clinical studies. The results of recent studies show a lot of variances in terms of duration of use, dosage, and individualized treatment management.

The main concern in the clinical use of P2Y12 is dual antiplatelet therapy (with aspirin and a P2Y12 receptor blocker) following intracoronary stenting to prevent stent thrombosis. However, there are also other multifactorial variables in terms of P2Y12 inhibitor use. In this chapter, current and precise medicines regarding P2Y12 inhibitor use are evaluated, from gene testing to escalation and de-escalation strategies. Taking all these into account, providing appropriate drugs selection considering treatment time, onset time, duration of use, side effect profile, treatment limitations, and evaluating and interpreting differences in clinical use based on randomized trials will shed light on coronary heart disease treatment choice.

Subject Index

Qualitative and Quantitative Investigation of Bio Tissues using Microscopy and Data Mining

The effects of glucose and salt on white blood cells, red blood cells, and

platelets (PLTs) in the blood of a leukemic patient by using a white light microscope

have been investigated for different concentrations (0 mM to 500 mM) of glucose and

salt. It has been revealed that the shape of erythrocytes, leukocytes, and platelets

changes and forms aggregates. Increasing the concentration of sodium chloride causes

an increase in the rouleaux formation and aggregation of platelets. The comparison of

CBC reports of these samples with and without analytes shows that total leukocyte

count (TLC) decreases gradually towards normal ranges of leukocytes, which is

favorable in the treatment of leukemia; at the same time, decreased level of hemoglobin

HGB, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin

concentration (MCHC) and increased level of red blood cell (RBCs) causes a reduction

in the oxygen supply, which is in favor of cancer growth and anemia.

In the second set of work, a computer-aided system was planned for automatic

classification of ultrasound kidney diseases and ultrasound liver (i.e., cirrhosis). Two

types of images were considered normal and chronic. By using the data mining

technique, the statistical features were extracted to differentiate between normal and

abnormal ultrasonic kidney images. By using feature extraction software (FES), a set of

statistical features were extracted from the region of interest of each image at different

frame rates. The data sets which were obtained using FES at different frame rates were

then classified by using Weka. These extracted feature results were classified by using

Weka and a 96.5% correct classification rate was obtained. The difference between the

values of these features was useful to identify between normal and abnormal images.

Molecular Pathogenesis of Human Coronaviruses of 21st Century

Coronaviruses affect both humans and animals, causing respiratory, enteric, hepatic, and neurological diseases. Until the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, coronaviruses were known to cause very mild infections in humans. However, the ongoing novel coronavirus disease (COVID- 19) that emerged in December 2019 from Wuhan, Hubei province, China, is several folds critical than the disease caused by its predecessors, SARS and MERS coronaviruses of 2002 and 2012, respectively. The evidence shows that all the human coronaviruses of this century, including the ongoing pandemic SARS-CoV-2, were the result of zoonosis, crossing the animal species barrier, causing high morbidity and mortality in the human population. A large number of studies have provided an understanding of earlier SARS-CoV and MERS-CoV induced pathogenesis and host immune response. Immunopathogenesis of current SARS-CoV-2 has also been reported to a significant extent since its emergence. It is evident from the studies reported to date that all the above three human coronaviruses share similarities with respect to clinical symptoms caused, pathological conditions induced, and host immune response that leads to the disease progression to a larger extent. However, certain pathological features associated with SARS-CoV-2 infection are distinct and fatal from the features caused by the other two human coronaviruses. This chapter focuses on the studies related to immune response, molecular pathogenesis of all three human coronaviruses with an emphasis on SARS-CoV-2 and the immune evasion strategies stimulated by individual viral proteins and their driven mechanisms.

Effects of Cinnamon on Health and its Potential as a Functional Food Ingredient

Cinnamon has been used as a spice in many societies for a long time, as well as for medical use. Botanical source, climatic conditions, and harvesting and production techniques alter the cinnamon’s quality and chemical components. However, the geographical origin of the cinnamon and the conditions under which it is processed affect the chemical composition. Essential oils derived from the bark, leaf, and root bark of Cinnamomum verum vary significantly in chemical composition. Cinnamon and its extract are known to have many positive effects on health, regardless of the type. In traditional medicine, cinnamon barks are used in many kinds of treatment methods of diseases, such as gastrointestinal system disorders, type 2 diabetes mellitus, lungs infections, cardiovascular diseases, cancer, and neurological disorders. For several decades, cinnamon has been used for its potential antioxidant, antimicrobial, anti-cancer, anti-inflammatory attributes. It is effective in controlling blood sugar and lipid levels. In this study, components, structures, nutrients of cinnamon were reviewed. Various food enrichment studies with cinnamon were reviewed, and the changes cinnamon caused in the composition of foods were examined.

Plant Molecular Pharming For Human Diseases

Infectious diseases pose an increasing threat to global health. The world has experienced many outbreaks due to Emerging Infectious Diseases (EIDs) in the 21st century. Vaccination proves to be the most successful public health intervention to counter such outbreaks. Vaccines against many diseases are available. Most of these vaccines either consist of live or attenuated strains, thus posing health risks. There is a need for new and safe vaccines to prevent and mitigate the impact of outbreaks due to emerging and endemic infectious diseases. The requisition of plant-based medicine is increasing day by day because of their non-toxic nature with no to very few side effects and readily available at a reasonable cost. In the present chapter, we will discuss the importance of plant molecular pharming (PMP) with its perspective on human diseases. Several advantages of PMP in relation to the United Nations’ sustainable development goals (SDGs) will also be deliberated.

Analysis of Cross-Reactivity, Specificity and the Use of Optimised ELISA for Rapid Detection of Fusarium Spp.

Many strides have been made in the development of antibody-based detection systems for rapid and sensitive analysis of Fusarium pathogens and their toxins. Antibody cross-reactivity, specificity, and binding affinity with antigenic molecules affect the efficacy in which these molecules serve their own functions. Researchers are, therefore, directed in investigating the principles that govern crossreactivity, specificity, and the relationship between them, using various tools such as optimised ELISA. This is important because the ability of Fusarium spp. to infect and produce mycotoxins in agronomic crops passes these toxins to animals and humans after contact or ingestion. Antibodies that recognise and bind particular antigens with great affinity and specificity, especially for the effective relief of unwanted Fusarium pathogenic materials in humans and animals, are thus required. Furthermore, the demand for fungal contaminants free agriculture, emerging antifungal drug resistance, and the fatal health effects of fungal infections in immunocompromised humans and animals drive the need for the development of a rapid, sensitive, reliable, and accurate relief system for these pathogens. Therefore, this chapter provides a succinct review on the role of antibody cross-reactivity and specificity, with reference to basic principles, challenges, and detection for rapid and reliable assessment in Fusarium pathogens.

Gene Therapy and Editing for the Treatment of Single-Gene Pain Disorders

It is a well-known reality that genetic variants can alter the pain perception of an individual in correlation with painless and painful voltage-gated Nachannelopathies for the better understanding of molecular transmission and detection events to noxious stimuli. Mutations in Nav 1.7 gene coding for the Na-ion channel can cause severe syndromes of distinctive pain such as small-fiber neuropathy, inherited erythromelalgia, and paroxysmal pain disorder. Whereas the inactivation of SCN9A mutations that encodes Nav 1.7, as a consequence, leads to insensitivity to pain congenitally. The TRPA1 heterozygous mutations code for Nav1.9 (SCN11A) and Nav1.8 (SCN10A) can cause insensitivity to pain while other variants are responsible for the potential-cation channel of the transient-receptor which can cause episodes of familial pain syndromes. Moreover, recently found few other novel genetic polymorphisms essentially identify the severity and complexity of the pain phenotypes. Various pain models for a better understanding of the sensory disorders and heritable disorders of pain are in the developmental phase. Therefore, devising new therapeutic approaches, genome-guided therapy, and understanding the structure of receptors for novel drug development and delivery in correlation with Na-ion channel is imminent.

Sodium Channelopathies and Novel Viral/non-viral Vectors for their Gene Therapy

Channelopathies are a group of neurological disorders that is caused by various genetic or acquired factors. In this disease, ions channels, a transmembrane protein channel responsible for the regulation of electrochemical gradient in the neuronal cells are disrupted. The disruption leads to myriads of neurological havoc due to abrupt synaptic transmission, voltage potential, and hyperexcitability of ions channels. Defective ions channels expedite the development of various disorders i.e., migraine, epilepsy, small fiber neuropathy, erthemalgia, paroxysmal pain disorder, dravet syndrome, and congenital insensitivity to pain, and others. These defects are commonly caused by deleterious mutational events in the ion channel gene encoding regions (SCN9A, SCN10A, and SCN11A). These regions encode for alpha subunits of sodium voltage gated channels (NaV 1.7, 1.8, and 1.9) that have notable importance in normal neuronal functioning. In these regions, usually, missense mutations are observed that cause improper protein folding making sodium channels excited for longer periods. The excitation is mainly manifested in peripheral and sympathetic neurons that contribute towards the development of chronic or acute pain or no pain sensation at all. There are several studies in the pipeline trying to elucidate the molecular mechanism of pain in relation to channelopathies. The lack of efficient pain models and shortcomings in the ill elucidate nature of the disease is somehow impeding the progress and development of novel therapies. But the existing literature revealed various pathways and targets that could be fruitful for different gene therapy interventions as opioids, analgesics, and non-steroidal anti-inflammatory drugs used to treat these conditions are imposing significant side effects and cellular proteins are developing resistance for these molecules, hence making them obsolete.

Anthelmintic Drug Discovery: Current Situation and Future Perspectives

Nematode parasites cause several neglected tropical diseases in humans such as lymphatic filariasis, onchocerciasis (river blindness), and soil-transmitted helminthiasis. Approximately 30% of the human world population is infected with at least one parasite and this prevalence could be even higher in rural areas and lowincome countries. Although nematode infections are rarely lethal, they are associated with morbidity and severe consequences, particularly in children.

There are several concerns about the management and treatment of these diseases. Currently, the repertoire of nematocidal agents is limited, and these drugs are not 100% effective against all nematode parasitosis. In addition, the extensive use of these few drugs in massive administration campaigns in humans would probably lead to the development of resistance very soon. Further worsening the situation, the interest of the pharmacological industry in developing novel anthelmintics is low since these infections are mostly endemic in poor countries that do not constitute a profitable market. Under this alarming scenario, there is an urgent need to develop new and broad-spectrum antiparasitic drugs.

Traditional preclinical drug discovery is a long, expensive, and complex process. Thus, innovative strategies and alternative models, such as the free-living nematode Caenorhabditis elegans, are required to reduce costs and accelerate times. Its genetic amenability and the feasibility of performing high-throughput screening assays, convert this nematode into an excellent platform for nematocidal drug screening.

This chapter summarizes the current situation on antiparasitic drug discovery and discusses the use of C. elegans at the initial steps of drug development to accelerate the appearance of new drugs.

Antiviral Activity of Vitamin D and COVID 19: Current Understanding

Innate and adaptive immune responses, which are intimately related to the evolution of many infectious diseases, are influenced by the biologically active form of vitamin D. From a mechanical perspective, there are several rationales to assume that vitamin D positively modifies host responses to SARS-CoV-2, either in the early infection or subsequent hyper-inflammatory stages of COVID-19. It has been long known that vitamin D metabolites induce antiviral effects through indirect and direct mechanisms via antimicrobial peptides, immune modulation, the interaction between major viral and cellular particles, initiation of apoptosis and autophagy, and diversity of hereditary and epigenetic aspects. The remarkable overlap between the deficiency of vitamin D and risk factors for severe COVID-19, including obesity, aging, and Black or Asian ethnicity, has motivated researchers to assume that supplementation of vitamin D can be promising as a preventive or treatment agent for COVID-19. Since the outset of the pandemic, researchers have integrated literature searches and crosssectional statistical studies to appraise the vitamin D level impact of COVID-19, whereby nearly 30 observational studies have confirmed that the incidence, severity, and mortality of COVID-19 are inversely related to the serum 25OHD concentrations. Also, some recently announced clinical trials indicated that vitamin D supplementation has a positive effect on the severity of COVID-19; however, other studies, including clinical trials, have not supported that, especially if we take into account what was revealed in a recent clinical trial, i.e., airway diseases are related to the irregular metabolism of vitamin D increasing the potential of developing vitamin D deficiency due to pulmonary inflammation. Therefore, more dedicated studies are required without critical limitations to ascertain the actual effect of vitamin D in preventing and treating COVID-19, and if its effectiveness is proven, the effective dose must be determined.

Pharmacotherapy of Emerging Antiviral Agents

Anti-infective agents have been one of the greatest accomplishments of modern medicine, which has led to a decrease in the number of deaths caused by various infectious diseases. The anti-infective agents are a broad family consisting of antimicrobials, antifungals, antimalarials, antiprotozoal, antituberculosis, and antiviral agents. Viral infections have caused millions of casualties worldwide, leading to the need for the development of effective antiviral agents. Although the replication mechanism differs significantly between the viruses, all viruses undergo steps like attachment, entry, genome replication, gene expression, and assembly for the release of the virions into the body of the host. Treatment with antiviral agents is essential for blocking the replication of the virus, and the currently available antiviral therapies are directed according to the disease. Furthermore, the treatment with antiviral agents aims to eradicate the viral pathogen from the host and prevent the clinical manifestation. Infectious diseases, such as human immunodeficiency virus (HIV), hepatitis B, and hepatitis C virus (HBV and HCV), and influenza, are of significant global concern. On the contrary, the outbreak of newer strains of influenza virus and Zika virus, Ebola virus, strains of coronavirus (CoV) like severe acute respiratory syndrome (SARS – CoV), Middle East respiratory syndrome (MERS – CoV) and novel Coronavirus (2019-nCoV) are life-threatening viral infections that exhibit major challenges to the humanity. As of date, multiple effective virostatics that target specific viral replication steps are approved for the treatment of viral infections. However, the use of such agents is restricted given the rapid emergence of antiviral resistance, which remains a major concern of current antiviral therapy. In this chapter, we summarize recent antiviral agents that show promising clinical benefits in various phases of clinical trials and also consider them as potential therapeutic agents in the future. Besides, we highlight and analyze the development of novel inhibitors targeting various stages of the viral life cycle that act by distinct mechanisms against current and emerging viral infections. Many antiviral drugs currently available are based on the concept of traditional chemotherapy. Nevertheless, new developments and advances in molecular biology have opened up possibilities to alternate treatment approaches. Clinical trials to evaluate gene silencing mediated by small interfering RNA (siRNA) and antisense RNAs expression against infection with a respiratory syncytial virus (RSV) have recently been initiated. Moreover, in–vitro studies of antisense RNA or siRNA technology have shown promising results in various virus strains. Despite the recent advancements, the development of targeted delivery of antiviral RNA molecules remains a major challenge since DNA viruses and retroviruses can incorporate their genomes into human genomes. To emphasize, antiviral drugs against particular target proteins have been effective in the treatment of prevalent infectious diseases such as HIV and HCV. Thereupon, broad-spectrum antiviral drugs instead of antivirals against specific virus infections need to be designed. With the rapid development of in-silico tools and gene modification strategies, antiviral drugs with better therapeutic index and safety profile will be developed against infectious diseases in the future. In fact, the effective design of newer antiviral drugs will reduce the possibility of emerging antiviral resistance.

Monoclonal Antibodies as Therapeutic Agents for Inflammatory Diseases

Inflammation is a physiological process caused when an agent (chemical, biological or physical) transcends the primary defense barrier of an organism, setting a series of biological reactions to restore the integrity of such organism, thus playing a central role in the fight against those pathogens. Uncontrolled amplification of these events may lead to undesirable pathological manifestations such as cancer, diabetes, and cardiovascular, neurological, and chronic inflammatory diseases. Monoclonal antibodies (mAbs) were first described in 1975, and since then, they have proven to be relevant therapeutic agents in a myriad of diseases. The US Food and Drug Administration (FDA) has already approved more than 90 mAbs for the treatment of several diseases, from which approximately 26% were specifically approved for the treatment of inflammatory diseases, for instance, rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, psoriatic arthritis, and palmoplantar pustulosis. This chapter provides an overview of the inflammation process and main biochemical mechanisms, together with a vision on the current state of the art of the mAbs-based biopharmaceuticals market and their application as powerful therapeutic agents for inflammatory diseases.

Comorbidities Inducing Mild Cognitive Impairment, an Evaluation of the Risk Caused by some Pathological Conditions

Mild cognitive impairment has usually been associated with aging, however, in recent decades with the increase in the prevalence of pathologies such as obesity, diabetes mellitus, cardiovascular diseases, and even spinal cord injury, it has become evident that a significant percentage of people who suffer from one or more of these diseases are at greater risk of suffering from some level of cognitive impairment that can lead to the development of various types of dementia. In this chapter, we review the main characteristics and mechanisms that promote the development of this type of alteration in each of the mentioned pathologies and briefly describe the various ways in which they have been approached.

Subject Index

Advancements of Transdermal Patches in Psychiatric Disorders

Non-adherence and non-compliance to the course of psychiatric medications affect the standard treatment plan of a patient. Inability to monitor the correct time and dosage also results in lesser efficiency of the drug and its action mechanism. Factors that may cause instability and non-compliance with the treatment plan are the possible side effects of drugs or the ease of use. With technological advancements in the field of drug delivery, transdermal patches, while Being non-invasive, ensure proper dosage and delivery of drugs through the skin, minimizing the first-pass metabolism. This review examines the existing literature, working mechanism, preclinical studies, and advancements in the application of transdermal patches in psychotropic drugs and deaddiction while evaluating various psychiatric disorders and comparing their efficacy and remission rate concerning standard oral treatment. It also addresses the challenges, drawbacks, and strategies required to increase its efficiency in clinical use.