Compartment Syndromes

Common Surgical Procedures in Geriatric Patients

Demographic studies show that life expectancy for people in the USA has been trending upwards for the past several decades. As the population ages, the number of geriatric patients who will require surgery has also increased. Information from the National Hospital Discharge Survey reported that in 2006, 35.3% of all inpatient procedures and 32.2% of all outpatient procedures were in patients aged 65 and older. Common elective surgeries in elderly patients include cataract and lens procedures, spinal fusions and laminectomies, and total or partial hip and knee replacements. Common urgent surgeries in this population include thoracic and abdominal cancer resections, breast and prostate cancer resections, and cholecystectomies. Finally, common emergency surgeries in the elderly population include hip fracture repairs and other geriatric traumas.

Subject Index

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.

Biomaterials and Mesenchymal Stem Cells

Mesenchymal stem/stromal cells are splendid cell sources for tissue engineering and regenerative medicine attributed to the unique hematopoietic-support and immunomodulatory properties as well as the multi-dimensional differentiation potential towards adipocytes, osteoblasts, and chondrocytes in vitro and in vivo. To date, MSCs have been identified from various approaches, such as perinatal tissues, and adult tissues, and even derived from human pluripotent stem cells (hPSCs). Longitudinal studies have indicated the ameliorative effect and therapeutic efficacy upon a variety of refractory and recurrent disorders such as acute-on-chronic liver failure (ACLF), acute myeloid leukemia (ACLF), premature ovarian failure (POF), and intractable wounds. To date, MSCs have been a to have various origins, including mesoderm, endoderm and ectoderm. In this chapter, we mainly focus on the concepts, and biological and therapeutic properties of MSCs, together with the standardizations for industrial transformation. Overall, the descriptions would help promote a better understanding of MSCs in disease pathogenesis and management and benefit the preclinical and clinical applications in the future.

Antihistamines, Proton Pump Inhibitors and Related Drugs

This chapter is a comprehensive account of the medicinal chemistry of antihistamines, H2 receptor (H2R) blockers, H3 receptor (H3R) blockers, and proton pump inhibitors (PPIs). It provides the mechanism of drug action and detailed structure-activity relationship (SAR) of the drugs in these classes to give the knowledge base for pharmacists. After studying this chapter, students will be able to:

• Describe the physiochemical properties of histamine and histamine receptors.

• Identify chemical classifications and describe the SAR of antihistamines, H2R and H3R antagonists.

• Differentiate receptor binding patterns and structural features between histamine receptor agonists and antagonists.

• Distinguish between sedating and non-sedating antihistamines, as well as the first-, second- and third-generation antihistamines.

• Describe the structural features of cromolyn and related mast cell stabilizers and their therapeutic applications.

• Discuss the proton pump inhibitors, including their development, mechanism of action, and structural and physicochemical features.

• Apply the medicinal chemistry principles to the clinically relevant case studies.

• Explain the drug discovery story of representative drugs of different classes.

Diagnosis and Potential Strategies to Discover New Drugs for the Treatment of Alzheimer’s Disease (AD)

Alzheimer disease (AD) is most common cause of dementia, which is characterized by impaired cognitive and behavioural charateristics. Deposition of Aβ plaques and neurofibrillary tangs (NFTs) are the hallmark of AD. Generally it is a chronic disease where neurodegeneration, and loss of neuronal function arise earlier before it is diagnosed. Early detection of AD is important as it reduces the severity of the disease. In this regard, an effective tools/methods are available including CSF biomarkers, Magnetic Resonance imaging (MRI), Positron emission tomography (PET) but all these methods are painful and often cannot be afforded by the patients.

Therapy of AD includes inhibitors of choline esterases, and antagonists at NMDA receptors. From the studies it is shown that these drugs just offer relief from symptoms rather than alleviating the progression of disease. Multiple pathological processes contribute for AD, like oxidative stress, dysregulation of neurotransmitters, inflammation of neurons, aggregation β-amyloid, phosphorylation of tau protein. It is essential to target multiple causes for an effective outcome in the treatment of AD. Early diagnosis is also crucial as it reduces disease progression thereby cost involved in AD therapy.

This review focuses on non-invasive, patient affordable diagnosis methods and also potential targets to discover new drugs beyond conventional and available drugs.

Glossary

Medicinal Plants: Traditional Trends to Modern Therapeutics

Medicinal plant therapies are becoming more common, as more people seek

natural cures and health approaches devoid of synthetic chemicals' adverse effects. The

biological and pharmacological potential of plants is studied and utilized all around the

globe for various purposes including the treatment of infections and diseases owing due

to bioactive compounds in plants produced as a result of secondary metabolism. The

study of medicinal plants is helpful in clinical trials to find pharmacologically useful

chemicals, and this method has produced thousands of valued medicines. Opium,

aspirin, quinine, and digoxin are some examples. Plants possess a large number of

bioactive compounds. On the basis of their chemical structure, they are divided into

four classes: alkaloids, flavonoids, tannins, and terpenes. Plants can now be turned into

“factories” that create therapeutic proteins, vaccines, and many more products for use

in the production of biotech pharmaceuticals, medications, and therapies. This chapter

discusses the diversity and importance of medicinal plants in various sectors as well as

highlights the successful drug products produced by the said entities and their future

trends.

Musculoskeletal System Examination

The musculoskeletal system constitutes a demanding part of the physical examination in terms of both knowledge and time. The skillful examiner focuses this critical task through information obtained in a careful history. The examiner should take the opportunity to observe the patient’s posture and mobility when he or she first enters the examination room. Musculoskeletal exam nearly exclusively relies on inspection and palpation of the joints and some specialized tests involving those techniques. Rarely do percussion and auscultation play a role in the musculoskeletal exam. The key features to note and record on the examination of the joints are swelling, tenderness, and loss of motion.

Application of d- and f- Block Elements and Their Compounds in Medicine

Biological Functions of d- and f- Block Elements

Biological Functions of Elements of Main Groups

Chromosome 21

The significance of human chromosome 21 is that the trisomy of human chromosome 21 causes Down syndrome in children. There are about 235 protein-coding genes on chromosome 21. Mutations like translocation in human chromosome 21 cause different conditions such as partial monosomy 21, core binding factor acute myeloid leukemia, ring chromosome 21, and other types of cancers such as acute lymphoblastic leukemia. Mutation in the DSCAM gene causes mental retardation and facial deformities in down syndrome. The human chromosome 21 also comprises the APP gene, where the expression of the gene causes Alzheimer's disease. The genes that are involved in causing Down syndrome and Alzheimer's diseases are also involved in cancer. This chapter discusses 63 genes of human chromosome 21 that are involved in different types of cancer.

Ethnobotanical use of Ayurveda to Treat COVID-19-Induced Respiratory Disorders

Respiratory tract infections are a major health problem in the entire world, especially due to corona epidemic in late 2019. Coronavirus spread-out throughout the world, and it causes the death of millions of people due to the precipitation of severity in respiratory disorders like respiratory neuromuscular, pulmonary vascular, and lung parenchymal disorders. All are the characteristic features of COVID-19 infection. The aim of the present review work was to summarize all existing ethnobotanical data on ayurvedic medicinal plants used in the treatment or management of respiratory disorders. Many known plant species are traditionally used to treat respiratory disorders & some plant species have been investigated for their therapeutic efficacy with positive results. This present study explored various offline & online databases for the literature on ayurvedic medicinal plants used worldwide to treat & manage respiratory disorders. A total number of 205 ayurvedic plant species used to treat & manage respiratory disorders worldwide has been documented. Most of the plants belong to Solanaceae, Asteraceae, Amaryllidaceae, Lamiaceae & Malvaceae.

Maternal Factors and the Placenta: A Programming Environment for Cardiovascular Disease

The risk of chronic diseases such as cardiovascular diseases (CVD) during postnatal life is not only determined by environmental factors in adulthood but also by intra-uterine and early life environment according to the Developmental Origins of Health and Disease (DOHaD) concept. Environmental insults including poor nutrition, oxygen availability, maternal stress, alcohol, smoking and drugs, can compromise the maternal uterine and lactational environment leading to short- and long-term adaptations in offspring physiology or programming. While short-term predictive adaptive responses may offer immediate survival value, they can lead to irreversible changes in embryonic/fetal tissues and organs mediated through changes in cellular signalling and metabolic pathways, as well as endocrine axes governing whole-body function. The capacity for developmental adaptation may also be determined by both genetic susceptibility and epigenetic mechanisms, as well as environmentally induced changes in maternal microbiome structure and composition. Basic mechanisms involved in the development of CVD have been described in previous chapters. Here we will focus on how mechanisms involved in developmental programming may contribute to CVD in adulthood.

Amphiphilic Nanocarriers to Fight Against Pathogenic Bacteria

The emergence and expansion of antibiotic resistance in pathogenic bacteria have become a global threat to both humans and animals. Immense use, overuse and misuse of antibiotics over several decades have increased the frequencies of resistance in pathogenic bacteria and resulted in significant medical problems. To fight against the widespread drug-resistant pathogenic bacteria has become a terrific challenge for the modern healthcare system. The major challenges to fight against pathogenic bacteria involve long-term antibiotic therapy with combinations of drugs. The abundance of resistance mechanisms in pathogenic bacteria has compelled many therapeutic antibiotics to become ineffective. As a result, the elimination of drug-resistant pathogenic bacteria requires a judicious strategy. The advent of nanotechnology has unveiled a new horizon in the field of nanomedicine. Nanoparticle-based techniques have the potential to overcome the challenges faced by traditional antimicrobials. In this way, self-assembling amphiphilic molecules have emerged as a fascinating technique to fight against pathogenic bacteria because of their ability to function as nanocarriers of bactericidal agents and interact and disrupt bacterial membranes. Nanocarrier-based drug delivery systems can mitigate toxicity issues and the adverse effects of high antibiotic doses. The focus of this chapter is to discuss various amphiphilic nanocarriers and their roles and possibilities in fighting against pathogenic bacteria.

Abnormalities of the Gastrointestinal Tract

Simulation Results of Sanitized Vehicle Parking System

Simulating a futuristic idea for the implementation of an innovative, efficient and economic sanitization-based parking system is the fulcrum of this paper. This paper depicts the simulation results of the previous chapter, “Sanitized Vehicle Parking System”, designed to solve parking problems and ensure customers' safety. Proteus 8 is the simulating software that has the ability to depict all the components used and their functionality in real-time. Arduino IDE is the coding platform incorporated with the Proteus 8 software. Arduino IDE has a lot of advantages over other platforms; one of them is extremely simple and flexible. This model will visualize the simulation results in detail which have been achieved and can be implemented in all the parking compartments with an upper hand over other parking systems by being completely automatic. Sanitization is the most crucial aspect responsible for the design of this system, as this parking system will sanitize all the automobiles entering the parking lot. This model has been divided into three compartments. The 1st section is responsible for sanitizing the vehicles entering the parking area. The 2nd section operates as the entry point of the parking area, automated through infrared sensors. Simultaneously the count gets incremented by 1, which gets displayed on the LCD Screen. The 3rd section operates as the exit point of the parking area. Each vehicle exiting from the parking area decrements the count by 1. Water- Level sensors are also employed to detect and measure the sanitizing fluid left in the vessel at different stages. The detailed simulation results for the sanitizing dispenser system are displayed on the LCD screen, indicating the next course of action in case of emptying the sanitizing liquid. The infrared sensors entirely handle the entry and exit points.

Biomass: A Sustainable Foundation for Bioenergy and Bioremediation - It’s Confronts and Scenarios in the COVID-19 Era: A Review

Various nations have distinct visions/missions and energy implementation strategies. Energy sources are essential to a nation's economic development and a necessity for all inhabitants. Several nations face varying degrees of energy catastrophe as a result of insufficient natural resources today mixed with the COVID-19 outbreak. This emergency led to the shutdown of numerous industrialized divisions exacerbated unemployment, constrained energy access, and associated societal shocks. A fundamental reason for these conflicts is the widening chasm between energy delivery and orders, financial issues, logistics, and irrelevant strategic planning considerations. The use of bioresources as a novel source of waste biomass was identified as a crucial criterion for bridging the gap and creating a vast outlook for an environmentally friendly biorefinery and bioremediation process. This presents a potential obstacle, as it suggests a replacement for fossil fuels in the production of specialty compounds and energy carriers. As a carbon-neutral mode/s, this reduces market anxiety and negative environmental repercussions. This ecological bioremediation with the use of biomass (phytoremediation), less expensive sorbents (for bioaccumulation and biosorption), and microorganisms (mainly agricultural byproducts) is more favorable than conventional ones.

Immunotherapy and Cancer Stem Cells

Immunotherapy is one of the important modalities in the treatment of cancer since it can directly target the tumor and its microenvironment with lesser side effects and cytotoxicity. The main goal of immunotherapy in the treatment of cancer is the reactivation of the immune system against cancer cells. In this way, the body fights against cancer using its immune system rather than relying on external agents which might be harmful to other healthy parts of the body. The development of monoclonal antibodies (Mabs) has delivered a significant therapeutic effect. Mab therapy is one of the most evolving techniques in cancer immunotherapy and has shown efficacy in controlling several types of malignancies. There are several other methods by which the activation of the immune system can be achieved, such as by using small molecules or by targeting ligands. Interestingly, studies have demonstrated that cancer stem cells have also been found as a target for effective immunotherapy. Additionally, the complete elimination of the cancer cells requires longer sustainability of tumor-specific T cells. Primitive results suggest that these T cells can be localized to tumor cells, mediating highly effective immunotherapy. However, despite these huge successes, several problems still persist and must be overcome. This chapter discusses the current and cutting-edge immunotherapeutic approaches to fight against cancer cells.

Biology of Cancer

Loss of genomic stability in the cell due to defects in the checkpoint of DNA damage, mitotic checkpoint, and telomere maintenance led to increased incidences of base pair alterations. Therefore, that genomic instability plays a critical role in tumor initiation and progression. Tumor progression requires a dynamic tumor/normal exchange in their microenvironment to support tumor growth. The histological alteration seen in the tumor at early stages confirms that the surface between the epithelium and the stroma undergoes progressive disturbance. Tumor progression is also affected by the immune system in which chronic inflammations promote the growth of tumor. Tumor cells experience altered metabolic profiling to support their growth. Cancer cells are characterized by uncontrolled cell division. For that, they utilize glucose as a source of energy to help them grow faster than normal cells. Hence, Glycolysis is a key metabolomics pathway consumed at a high rate during carcinogenesis.

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.

Taurine and the Mitochondrion

Several studies have evaluated the subcellular compartmentalization of taurine (TAU) and its cellular and molecular mechanisms of action. Meanwhile, it has been found that TAU is largely uptaken by mitochondria. TAU could improve mitochondrial function by incorporating it into the basic mitochondrial structures and protein synthesis (e.g., mainly mitochondrial electron transport chain components). Several other mechanisms, including the enhancement of mitochondrial calcium sequestration, regulation of mitochondria-mediated reactive oxygen species (ROS) formation, prevention of mitochondria-mediated cell death, and mitochondrial pH buffering, are also involved in the mitochondrial function regulatory properties of TAU. Therefore, TAU has been used against a wide range of pathologies, including mitochondrial injury. In the current chapter, a review of the approved molecular mechanism for the effects of TAU on mitochondria is provided. Then, the applications of TAU on a wide range of complications linked with mitochondrial impairment are discussed. The data collected here could give a better insight into the application of TAU as a therapeutic agent against a wide range of human diseases.

Taurine: Synthesis, Dietary Sources, Homeostasis, and Cellular Compartmentalization

Taurine (β-amino acid ethane sulfonic acid; TAU) is a sulfur-containing amino acid abundant in the human body. Although TAU does not corporate in the protein structure, many vital physiological properties have been attributed to this amino acid. TAU could be synthesized endogenously in hepatocytes or come from nutritional sources. It has been found that the source of body TAU varies significantly between different species. For instance, some species, such as foxes and felines, are entirely dependent on the nutritional sources of TAU. On the other hand, TAU is readily synthesized in the liver of animals such as rats and dogs. The TAU synthesis capability of the human liver is negligible, and we receive this amino acid from food sources. The distribution of TAU also greatly varies between various tissues. Skeletal muscle and the heart tissue contain a very high concentration of TAU. At subcellular levels, mitochondria are the primary targets for TAU compartmentalization. It has been found that TUA also entered the nucleus and endoplasmic reticulum. The current chapter discusses the synthetic process and dietary sources of TAU. Then, the transition of TAU to sub-cellular compartments will be addressed. Finally, the importance of TAU homeostasis in the pathogenesis of human disease is mentioned.

Diabesity and the Kidney

Diabetes Mellitus and obesity, now coined as “Diabesity”, is a worldwide epidemic that imposes a huge burden on healthcare and society. Diabesity has been associated with poor outcomes and increased morbidity and mortality. The kidneys are a vulnerable target of diabesity. In this chapter, we discuss the epidemiology, pathophysiology, and treatment of diabesity–induced kidney disease. We specifically focus on the therapeutic targets and pharmacological management of diabesity-related kidney diseases.

Arginine, Nitric Oxide, and Type 2 Diabetes

L Arginine (Arg), a semi-essential essential amino acid, has received significant research interest over the last two decades as nitric oxide (NO) precursor. Arg is widely used as a complementary treatment in various NO-disrupted conditions, e.g., hypertension, preeclampsia, and endothelial dysfunction. Here, we provide an overview of the potential efficacy of Arg as a NO precursor and its effects on glucose and insulin homeostasis and diabetes-induced cardiovascular complications.

Origin of COVID-19

Coronavirus is a type of virus that is surrounded by non-segmented, singlestranded, positive-sense RNA genomes that reproduce in the cytoplasm. The size of the coronavirus is usually 80-120 nm. It was discovered in Wuhan, China in December 2019, and it was termed 2019 nCoV or COVID-19. The coronavirus is encased in a lipid bilayer and it possesses several proteins. These proteins are surrounded in the envelope of a virus; whereas, in the viral RNA, N-protein shows interactions and it can be found on the outer surface of the viral particle, forming the nucleocapsid. The spike protein is identified as the leading protein and mediates the entrance inside the host body that would cause SARS-CoV-2syndrome. The spike protein has two spheres namely S1 and S2. The receptor that is attached to the S1 and further S2 is responsible for fusion. In the past, the most severe types of virus which had resulted in large-scale pandemics were SARS (in 2002–2003) which occurred in Guandong Province, China. Meanwhile, Saudi Arabia had experienced the Middle East respiratory syndrome (MERS) in 2012. The virus in the 1960s was commonly identified in birds and mammals; mostly in rats, camels, cats and bats. SARS-CoV-2 causative agents belong to the genus β-Coronavirus. Coronavirus can be classified into four genera such as α, β, γ, and δ coronavirus. Alpha and beta coronaviruses are found in mammals such as bats. Gamma coronaviruses would primarily infect birds and affect mammalians, whereas delta coronaviruses would infect both birds and mammals. This chapter highlights the origin, historical background, the classification of the coronavirus as well as providing the conceptual information on various treatment approaches for COVID-19.

Role of Vyana Vayu in CardioVascular System, Etiopathogenesis and Therapeutic Strategies: An Ayurveda Perspective

A systems approach to health is the hallmark of Ayurveda. It believes in preventing disease and maintaining and restoring health. The entire concept stands on three fundamental functional units-Vata, Pitta and Kapha, where Vata, mobilizes the other two units. Depending on their locations, Vata (Vayu) is classified into five subtypes, where each has its distinct role to perform. Vyana Vayu (VV), an important subtype of Vata, is synthesized in myocytes and responsible for the genesis of the action potential. A key regulator in contractile functions, VV propels out nutrients from the heart. It not only mediates intracrine and paracrine activities but modulates the vascular tone too. Wherever there is scope to flow, VV has its unique role to contribute. Ancient scholars of Ayurveda have identified its ubiquitous role in the endogenous system, where all the activities depend on VV. Hence, preventing VV from any stimulus is of paramount importance since they consequently lead to various cardio vascular diseases (CVD). Classical texts have addressed the prognosis in six discrete phases where each phase can be avoided strategically. Highlighting the precipitants that attenuate VV, we focus on addressing those phases along with curative measures so that the functions of Vyana Vayu can be restored.

Subject Index

Nutrient Cycling: An Approach for Environmental Sustainability

Nutrient cycling is an important environmental process and has been the focus of ecological research. Nutrient cycling refers to the sufficient supply of key elements provided through the ecological processes within and between various biotic or abiotic components of a cell, community, or ecosystem. Nutrient cycling also includes the recovery and reuse of industrial, agricultural, and municipal organic debris that are considered wastes. Nutrient cycles include biotic and abiotic components involved in biological, geological, and chemical processes known as biogeochemical cycles. Changes occurring in such cycles may indicate or even alter the functioning of the ecosystem. Plants take up soil nutrients in terrestrial ecosystems for healthy growth and development, wherein soil acts as a nutrient reservoir. Nutrients are lost from such sites due to soil erosion, denitrification, and food production, which cause reduced availability of nutrients. Therefore, analyzing nutrients’ assimilation, transport through biota, and their release for subsequent re-assimilation is mandatory. Nutrients to be recycled essentially for the survival of organisms include macronutrients (C, O, H, N, K, P, Ca, Mg, S, and Cl) and micronutrients (Fe, Mn, Mo, Cu, Zn, Bo, Ni, Co, Na, Se, and I). This chapter presents the role of nutrients and nutrient cycling for environmental sustainability

A Physiological Approach to Inflammatory Markers in Obesity

Obesity is one of the most critical health problems all over the world; it is associated with metabolic dysfunction and overnutrition. Changes in the physiological function of adipose tissue, leading to altered secretion of adipocytokines, inflammatory mediators release, and chronic low-grade inflammation, are seen in obesity. Macrophages, neutrophils, CD4+ and CD8+ T cells, B cells, natural killer T (NKT) cells, eosinophils, mast cells, and adipocytes are involved in the inflammatory response that occurs during obesity. Various inflammatory markers are released from these cells. In this chapter, we will mention inflammatory mechanisms and markers of obesity.

Biomarkers in Otorhinolaryngology

Biomarkers of otorhinolaryngologic diseases with higher insult over a person’s him/herself and overall health services are summarized in brief. In order to define, diagnose, treat and monitor any disease markers are needed. Otorhinolaryngology (ORL) is interested in special disease entities of the region besides otorhinolaryngologic involvements of the systemic diseases and unique forms of pathologies such as cholesteatoma, Meniere’s disease and otosclerosis. Neoplasia is another heading to deal with. In the following chapter, one will find an overview of molecules that have been used as a biomarker as well as the end points of the present research on the issue relevant with ORL. Day by day, new molecules are being named however, the pathways of action are rather the same. Readers will find the headings related to the most common diseases of the field, informing them about where to look for defining new strategies of understanding of each disease.

Clinical Application of Biomarkers for Hematologic Malignancies

Over the last decade, significant advancements have been made in the molecular mechanisms, diagnostic methods, prognostication, and treatment options in hematologic malignancies. As the treatment landscape continues to expand, personalized treatment is much more important.

With the development of new technologies, more sensitive evaluation of residual disease using flow cytometry and next generation sequencing is possible nowadays. Although some conventional biomarkers preserve their significance, novel potential biomarkers accurately detect the mutational landscape of different cancers, and also, serve as prognostic and predictive biomarkers, which can be used in evaluating therapy responses and relapses. It is likely that we will be able to offer a more targeted and risk-adapted therapeutic approach to patients with hematologic malignancies guided by these potential biomarkers. This chapter summarizes the biomarkers used (or proposed to be used) in the diagnosis and/or monitoring of hematologic neoplasms.

Subject Index

COVID-19 And Chronic Kidney Diseases

The SARS-Coronavirus-19 disease has emerged as a global health challenge and has engulfed almost all countries since it was first reported in Wuhan, China. Patients with CKD have not been spared from the wrath of this pandemic and are bearing the brunt of it along with the rest of the population. Most of the patients with CKD have underlying comorbidities like diabetes and hypertension and are at an increased risk of adverse outcomes. Some of the manifestations of COVID-19 include proteinuria, hematuria, AKI, and acute CKD, requiring various forms of renal replacement therapy. Multiple mechanisms proposed for this damage include direct invasion, cytokine storm, hemodynamic derangements, and many others that are still undergoing extensive research. Since SARS COV 2 enters the cells through ACE 2 receptors, there are concerns regarding the use of ACE inhibitors and ARBs in patients already on these drugs. There are concerns regarding the use of immunosuppressants in various immune-mediated kidney diseases (postponing planned doses of methylprednisolone/cyclophosphamide/rituximab). Hemodialysis patients are exposed to potential sources of coronavirus as they have to repeatedly report to hospitals for their dialysis sessions. Measures regarding safeguarding dialysis staff from COVID -19 are contentious issues, especially in resource-limited settings. Almost all renal transplant patients are on lifelong immunosuppressive agents, making them more vulnerable to infections. Therefore, CKD patients have unique issues in the management of COVID and CKD, which we need to understand to develop protocols for the management of these problems.

SARS-CoV-2 and Co-morbidities

In December 2019, cases of pneumonia emerged in Wuhan, China, which was indicated to be due to a novel coronavirus called SARS-CoV-2 or COVID-19. This virus shares a lot of similarities with the previous SARS-Cov and MERS-Cov, yet its spread has been recorded to be much faster, with more than 80 million cases and close to 1 million deaths in the USA by March 2022. Further, the CDC has released a list of health conditions that increase the risk of acquiring the virus and its severity by 12- folds. Those conditions include diabetes, cardiovascular diseases, chronic kidney disease, cancer, chronic obstructive pulmonary disease, sickle cell anemia, obesity, and immunocompromised states. The two common mechanisms increasing the susceptibility of patients with any of the aforementioned co-morbidities are 1) increased inflammation causing a “cytokine storm”; and 2) suppressed or delayed immune system response, which is expected to be highly responsive in infections. The “cytokine storm” is characterized by an increased release of cytokines that cause an impaired response of the macrophages and lymphocytes that are expected to be highly responsive under any state of infection. Further, these conditions are known to be states of chronic low-grade inflammation, which adds to the cytokine storm with the suppression of the immune response. This disruption equally influences the involvement of B-cells and T-cells in the resolution of infections. Finally, some conditions may suffer from disturbances at the levels of the respiratory system, such as difficulty breathing, accompanied by respiratory muscles inefficiency and inequality in ventilation perfusion, causing hypoxia and the increased need for mechanical ventilation and ICU admission. The objective of this chapter is to introduce the main chronic conditions mostly influenced by SARS-Cov-2, the severity of the virus, its prevalence among the recorded cases, and the consequence observed at the level of the immune system.

Subject Index

Specific Diagnoses and Management Principles of the Intestines and Lower Digestive Canal

Acute appendicitis, visceral perforations, diverticulitis (including bleeding and abscesses) acute calculous cholecystitis, acute ischemic bowel, mesenteric artery ischemia and infarction can cause acute abdominal conditions which prompt emergency interventions. Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) may be followed up in some time without remarkable complications, although at some point with abscesses, hemorrhagic diarrhea and acute abdominal syndromes. However, the differential diagnosis (DD) of patients presenting with acute abdominal pain is much broader than this, including many benign conditions as well. Some etiologies of abdominal pain such as cholangitis strangulated hernias, colonic diverticulitis, perianal/ perirectal abscesses and fistulas may progress and turn into lifethreatening conditions like abdominal sepsis without proper management.

Mitochondrial DNA Role in Zika Virus Infection

Zika virus (ZIKV) is a member of the Flavivirus family. ZIKV infection ranges from asymptomatic to a mild disease in adults. However, in 2015, ZIKV infection became a public health emergency in the Americas associated with neurological alterations such as Guillain-Barré syndrome (GBS) in adults and congenital zika syndrome (CZS). By blocking type I IFN interferon signaling pathways, ZIKV evades the immune system and infects cells expressing the T cell immunoglobulin mucin domain-1 (TIM-1) and TAM (Tyro3, AXL, and Mer) receptors, such as neural progenitor cells. Moreover, ZIKV seems to orchestrate a process of astrocytic hypoxia that leads to the production of reactive oxygen species (ROS), mitochondrial DNA (mtDNA) fragmentation, and apoptosis. In recent decades, the active participation of mitochondria in the immuno-inflammatory response has been reported in several pathologies. In this context, mtDNA seems to have an essential role in triggering the innate immune response by activating inflammasomes, activating the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, and also activating toll-like receptors that lead to IFN production and viral clearance. Here, we present an overview of some mechanisms of inflammatory response present in ZIKV infection, which contributes to mitochondrial dysfunction, mtDNA release, and tissue damage.

An Auspicious Bacterium: How Mitochondria can be Beneficial to the Innate Immunity through Aerobic Exercises

Mitochondria are highly relevant organelles with regard to their unique function in generating energy and contributing to metabolism within the cell. Furthermore, recent studies suggest that they might have an influence on the innate immune and inflammatory responses, thus affecting antiviral immunity (as example: Zika virus (ZIKV), hepatitis C virus (HCV), dengue virus and SARS-CoV-2 virus) and antibacterial immunity as well (Streptococcus pneumoniae, Mycobacterium leprae and Mycobacterium tuberculosis). Therefore, this chapter aims at bringing a relevant debate about the role of mitochondria and their multifunctional capacity. We intend to discuss the complexity of mitochondrial metabolism, especially during aerobic physical exercises, which causes the modulation of the gene expression of proteins that lead to mitochondrial proliferation and, thus, promote health. In addition, considering the injuries caused by hypoxia, this chapter also stresses the enormous potential of mitochondria to enable the survival of eukaryotic cells by allowing them to turn to aerobic respiration, as shown in previous scientific studies. In conclusion, this chapter points out the importance of mitochondrial biogenesis (both natural and stimulated biogenesis by aerobic exercise) and the benefits this organelle brings to the health, arguing that they go far beyond cellular respiration and oxidative phosphorylation.

Extracellular Biosynthesis of Gold and Silver Nanoparticles using Fungal Extracts

Nanoscience has opened new vistas to manage phytopathogens, improve crop productivity by the development of new varieties, and control infectious diseases in humans. Silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) are highly acclaimed for their wide potential application in various fields. Chemical and physical methods of synthesis of AgNPs and AuNPs are widely used; however, such methods possess numerous setbacks, such as the production of toxic residues and indispensable need for high energy. Biosynthesis of nanoparticles is a cost-effective and environmentally friendly method. A plethora of species of plant, bacteria, fungi, etc. is available with potential biosynthesis ability. Fungi are a highly preferred organism owing to the ability to secrete a large number of extracellular enzymes, metal toxicity tolerance and bioaccumulation ability, and ease of handling of its biomass. Extracellular enzymes act both as reducing as well as capping agents. Two different methods are used by fungi for synthesis viz., intercellular and extracellular synthesis. Extracellular synthesis is preferred over intercellular as it bypasses several down streaming processes. During the reduction process, the metal ions (Ag2+ and Au3+) are converted to an elemental state (Ag0 and Au0 ) which is in the nano range. Due to their large surface-to-volume ratio and other properties, they become very effective against other pathogens. There is an excellent prospect of the use of nanoparticles in the field of agriculture and health and nanoparticles synthesized using a biological method involving fungi could be a boon.

Pharmaceutical Nanoscience: Pulmonary Drug Delivery System

Pulmonary diseases impose an immense burden on global health. Asthma, cystic and idiopathic pulmonary fibrosis, pulmonary hypertension, lung cancer, and chronic obstructive pulmonary diseases (COPD) are among the diseases that require efficient pulmonary drug delivery. Targeted-drug delivery refers to the delivery of a drug or a therapeutic agent to a certain tissue or organ; this can be achieved through pulmonary drug delivery (PDD) with nanomaterials. Nanomaterials are made from polymers, ceramics, metals, and biological materials into different sizes and structures. Nanomaterials for PDD entail nanoparticles of therapeutic ingredients, including herbalbased drugs and nanocarriers of the therapeutic bioactive substance. These types of materials used in managing pulmonary diseases are discussed in this chapter.

Introduction to Nanotechnology and Herbal-Based Nanoparticulate Systems

This introductory chapter reviews the history of nanotechnology and its benefits and challenges in the pharmaceutical field. In general, the chapter summarizes the types of nanoparticles and the techniques used to formulate nanoparticles. In detail, it discusses the principle of nanotechnology in improving solubility and dissolution rate. It discusses and describes different types of nanoparticles, including polymeric, metallic nanoparticles, and other types, such as solid lipid nanoparticles (SLN) and liposomes. Nanosization can be performed by various techniques, including top-down, bottom-up, and combination techniques. The method of these techniques has been discussed in this chapter. One of the disadvantages of nanoparticles is their stability. Nanoparticles suffer from various types of instability problems, including aggregation, sedimentation, and crystal growth. Therefore, in this chapter, the authors discuss the problem of stabilization of nanoparticles and describe the different pathways of physical instability and the mechanism of stabilizers to stabilize the colloidal system. Finally, the importance of herbs and natural products in the medical field and how the use of nanotechnology addresses various drawbacks of herbal products are also discussed.

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.

Pediatric Pain Management and Regional Anesthesia

Inadequate pain management in children not only leads to immediate stress and suffering, but it can also influence long-term psychological, physiological, and emotional outcomes for the patient and family. It is well-established that neonates not only feel pain, but also have an exaggerated perception due to immaturity of the descending inhibitory pathways. In addition, various physiologic differences influence the effect and duration of various medications. Despite the existence of many validated tools and pain scales, the assessment of pain in children is challenging. Successful acute pain management targets various elements in the complex system of pain transduction, transmission, modulation, and perception. A multimodal approach targeting multiple steps in the nociceptive pathway is more effective than those involving a single target. Regional analgesic techniques supplemented with opiates and nonopioid medications have proven to be effective in controlling postoperative pain. Traditionally, caudal and epidural analgesia have an established record of safety and are popular regional techniques in children. However, advances in ultrasound-guided techniques have encouraged pediatric anesthesiologists to perform more regional blocks in children. Additionally, application of the enhanced recovery after surgery (ERAS) protocol for major surgeries and concern about the opioid epidemic has led to increasing awareness about the benefits of regional anesthesia. In this chapter, we will discuss the fundamentals of pain perception in children, the assessment of pain and the multimodal approach to manage it, relevant pharmacology, and various regional techniques in routine and complex pediatric surgical patients.

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.

New Technologies Used for The Study of Diabesity and Related Pathologies. The Most Relevant Analytical Techniques and Laboratory Equipment

To tackle diabesity, medical research hopes that treatments will be personalized, and to reach this objective, it will be necessary to develop new equipment and analytic techniques. A proper assessment of diabesity requires blood glucose and body composition monitoring. Although with the ongoing application of new technologies, as in the case of the omics techniques, the possibilities for early diagnosis and personalized treatments of diabesity patients are perhaps even closer than we think. Today, the evaluation of diabesity is more accurate due to discovering novel biomarkers and the rapid advances in gene expression profiling, epigenetics, metabolomics, or microbiome analysis. It is, therefore, essential to keep up with the new technologies used for the study of diabesity and its related pathologies

Safety and Effectiveness of the Endoscopic Rhizotomy for the Treatment of Facet-Related Chronic Low Back Pain

Lumbar spinal facet joints may be a significant source of chronic low back pain, with a reported prevalence of 7.7 to 75%. The clinical entity has been called facet joint syndrome. However, this syndrome and its therapies remain controversial as the clinical evidence for its treatment has been graded as weak. Intra- or periarticular injections have found acceptance as a diagnostic tool. Its etiology may be multifactorial, with degeneration of the joints’ cartilage being the likely leading cause. This process incites an inflammatory response involving the synthesis of proinflammatory cytokines and metalloproteinases. Hence, local injections of glucocorticoids into the affected joint has become an accepted short-term treatment option but with weak long-term benefit. In this chapter, the authors review their clinical experience with the endoscopic rhizotomy when treating chronic low back pain due to facet syndrome. Its safety and effectiveness were evaluated in 84 patients, including 48 females and 36 males with a mean age of 65, ranging from 52 to 82. Patients were included in the study if they reported greater than 80% pain relief with lumbar medial branch blocks using ropivacaine on two separate occasions. Primary clinical outcome measures were the VAS BACK score and the Oswestry Disability Index (ODI). There were no adverse events and complications except one patient with a postoperative hematoma, which resolved with conservative care. At the final six months follow-up, the VAS scores were significantly lower (postop VAS 2.3; range 0 - 4) than before endoscopic rhizotomy (preop VAS mean 6.4; range 4-7; p < 0.05). The postoperative ODI of 24 (range 12 - 48) was significantly lower than its preoperative value 52 (range 42-67). The authors conclude that dorsal endoscopic rhizotomy is safe and effective for facet-related low back pain.

Mobile Outside In, SCOT (Suprapedicular Circumferential Opening Technique) Approach for Highly Inferior Migrated HNP

Downward migrated lumbar disc herniation can present a challenge to any spine surgeon. Open spine surgery requires an aggressive decompression of the posterior bony elements, which ultimately may lead to postlaminectomy syndrome and instability – both of which have been associated with higher reoperation rates. The interlaminar endoscopic approach is a reasonable alternative to open translaminar surgery but still carries the risk of dural tear and does not afford the ability for an intradiscal discectomy. The authors offer a modification of the outside-in transforaminal approach - the suprapedicular circumferential opening technique (SCOT) to gain better access to downward- and far-migrated extruded lumbar disc herniations.

Regulation of Food Intake: Central Mechanisms

Food intake is regulated by complex hypothalamic neuronal systems

originally identified as hunger and satiety centers. The search for the underlying

mechanisms led to the discovery of several central orexigenic and anorexigenic

peptides. The present chapter summarizes the current knowledge about the role of

classical hypothalamic neuropeptides such NPY/AgRP, POMC/CART, melanocortin,

and orexin system, as well as several new central signals such as AMPK, ncRNA, and

autophagy involved in the regulation of appetite and food intake.

The Cell: The Basic Functional Unit of Life

Cell is the smallest and the basic functional unit of life. Every organism,

whether prokaryotic, archaeans, or eukaryotic, is composed of a basic building block

which is the Cell. A cell consists of a cell membrane, a nucleus, and a cytoplasm where

intricate arrangements of fine fibers and organelles lie. Cells are specialized for a

specific purpose, they form tissues which in turn form organs, and several organs make

up the system, and several systems that function together form the organism. The

present chapter aims to describe the body, tissues, system, organism, and the structure

and function of the major cell organelles with a focus on eukaryotic cells.

Overview of Traditional Uses, Phytochemistry and Pharmacology of Peganum Harmala L.

Mother Nature acts as a source of a variety of therapeutically important

plants that have been used directly or indirectly for the wellbeing of the human race. In

addition, these plants have also been well known for their applications, especially in

agriculture, pharmaceuticals, cosmetics, aroma, food flavors, and food preservatives.

These therapeutically important plants are also used by local and tribal peoples as a

remedy to cure various infectious illnesses since the dawn of civilization. These

medicinal plants serve as a source of eco-friendly drugs that are potentially less toxic as

compared to a variety of synthetic drugs. Peganum harmala L. belongs to the genus

Peganum and the recently separated family Nitrariaceae and is now officially included

in the family Zygophyllaceae. The plant grows primarily in dehydrated and amorphous

conditions, mostly in Africa, Iraq, Uzbekistan, Tajikistan, Russia, China, Afghanistan,

Pakistan, and India. The genus Peganum comprises six species and P. harmala L. is the

most explored plant of the genus. The plant is widely known for its pharmacological

potential such as antiviral, antibacterial, anticancer, antioxidant, anti-inflammatory,

antidepressant and anti-diabetic, etc. The wide range of applications of the plant can be

attributed to its secondary metabolite composition consisting of alkaloids, flavonoids,

triterpenoids, anthraquinones, volatile oils, and dietary components (proteins, fatty

acids, vitamins, and minerals). Harmalol and harmine are two key beta-carbolines,

which are isolated from different parts of the plant and are mainly responsible for the

diverse array of pharmacological potential of the plant. Owing to this, these betacarbolines

serve as an active ingredient for the production of different drugs, which are

used to treat various illnesses viz. common cold, diarrhea, ulcer, arthritis, asthenia,

depression, and dermatologic problems related to hair and skin. These are also effective

against Parkinson’s disorder and various cancers. Furthermore, different parts of P.

harmala L. also act as a source of various macro and micro minerals, which are
essential for the smooth functioning of the human body. The aim of the present chapter is to

summarize the various traditional uses, pharmacological properties and phytochemistry

of P. harmala L.

Hibernation or Transformation? Challenges in Cardiovascular Drug Development

The decline in deaths from cardiovascular diseases in line with scientific developments between 1950-2010 was impressive. Despite these significant advances, cardiovascular (CV) diseases remain the leading cause of death worldwide. According to the World Health Organization (WHO) data, 17.9 million people die due to CV diseases every year, which corresponds to 31% of the total deaths worldwide. Therefore, for many CV diseases, there is still a need for improved treatment, and this is only possible with the development of new drugs.

Although investments in the previous decade have resulted in the development of many innovative drugs in the treatment of CV diseases, today, pharmaceutical companies are less enthusiastic about developing CV drugs, mainly due to financial and regulatory difficulties. Indeed, today, institutes, associations and even organizations such as WHO are taking over the sponsorship role that pharmaceutical industry players have abandoned. In parallel, cardiovascular pipeline activity is shifting from large pharmaceutical companies to small and medium-sized companies and from fastfollowing drugs to first-in classes. This transformation in CV drug discovery and development reveals significant challenges that require square up to. The aim of this chapter is to discuss the global challenges faced in CV drug discovery and development to find effective solutions.

Potential Nanoformulation Approaches for Delivery of HCC Therapeutic Agents

Hepatocellular carcinoma (HCC) is a major cancer type worldwide. The

major challenge with HCC is that it is usually detected at an advanced stage. After the

launch of the first drug Sorafenib against HCC in 2007, several other small molecules

and monoclonal antibody-based drugs have been launched to fight against HCC.

However, the survival rate in HCC is still very poor. This indicates that there is still a

necessity for more effective therapy or to increase the efficacy of the existing therapy.

Nanoformulation approach refers to such formulation approaches where the particle

size of individual particles or vesicles in a formulation range between 1-1000 nm. The

individual particle or vesicle could be either single drug particles or

nanosphere/nanocapsules having drug entrapped in polymer/lipid matrix or drug

connected with metal or metal oxide core. The idea of using nanoformulations for drug

targeting first came around the 1950s. Since then, countless research groups across the

world have advanced the field to the extent that several products based on the

nanoformulation approach have been launched on the market. Besides targeting,

nanoparticles can also help circumvent biopharmaceutical challenges of drugs, such as

dissolution, limited oral bioavailability issue, or formulating “hard to solubilize” types

of molecules for parenteral formulation. This chapter will review different

nanoformulation approaches that can be potentially applied for HCC therapy, their

manufacturing process, and therapeutic benefits. We will review the application of

different nanoformulation approaches for HCC specific therapeutic agents.

Aptamers and Their Potential in Site-Specific Nanotherapy Against Hepatocellular Carcinoma

Globally, hepatocellular carcinoma (HCC) is one of the most devastating

neoplasia and has a remarkably high mortality rate. Furthermore, the long latent period

associated with HCC lends the diagnosis at the intermediate or advanced stages where

the chemotherapy is the solitary therapeutic intervention. The responsiveness of HCC

towards conventional chemotherapeutic agents is notably poor due to multiple factors.

Among them, multiple drug resistance, reduced drug concentration at the tumor site,

quicker clearance, and non-specific distribution are the prime causes leading to

remarkably high off-target toxicity and mortality. More importantly, the approval of

several multikinase inhibitors (MKIs) by the United States Food and Drug

Administration (FDA) for the treatment of HCC as targeted therapeutics has been

found to be inadequate to make a notable impact on survival. Therefore, ligand-based

targeted therapeutics capable of delivering the therapeutic modality specifically into

neoplastic hepatocytes have been explored extensively by researchers worldwide.

Among the plethora of HCC-targeting ligands, aptamer-based targeted therapeutics in

HCC have gained significant momentum compared to others due to some signature

characteristics of aptamer, namely non-immunogenicity, low cost, non-toxicity,

thermostability, simpler manufacturing, and high suitability for chemical modification.

Despite their enormous potential, aptamer-based targeted therapeutics are still in

infancy and require smarter thinking and quick translation from e-clinical to clinical

application. Thus, the fundamental focus of the book chapter is to highlight promising

features of aptamers, their production, chemical modification, mechanism of action,

and finally, detailed emphasis has been given on the overall scenario of aptamer-based

targeted therapeutics in HCC.

Nanotherapeutics for the Treatment of Hepatocellular Carcinoma

Currently, hepatocellular carcinoma (HCC) is the third leading cause of

mortality among cancerous diseases. It is a primary type of liver cancer possessing

unique features like solid malignant tumor type growth, leaky vasculature, and

angiogenesis. The success of conventional treatment in the management of HCC is

constrained due to unresponsiveness to particular approaches, drug resistance, systemic

side effects, and recurrence of malignancy. The development of nanotherapeutics offers

an impending key for overcoming these challenges. Nanotherapeutics utilizes

nanosized or nanostructured materials to attain particular therapeutic and

pharmacokinetic purposes. The diverse targeting strategies and site-specific drug

release patterns of this approach enlighten the hope for effective management of HCC.

Scientists have developed several nanomaterials like nanoparticles, nanogel, and

liposomes to deliver chemotherapeutic agents specifically to HCC sites with improved

efficacy, safety, and selectivity. Active targeting has remained most common and

effective in HCC management among active, passive, and stimuli-responsive targeting

strategies. Hopefully, some nanoformulations for HCC treatment have proved their

promising effects in clinical trials. In this chapter, an attempt is made to illustrate the

overview of HCC, the impact of nanotherapeutics, along with recent developments,

suitability, and challenges of various nanotherapeutic approaches for HCC

management.

Subject Index

Broad-Spectrum Antivirals to Combat COVID-19: the Reality and Challenges

Viral infections, which lack effective treatment, have posed an ongoing threat to human health. Most approved antiviral agents selectively target a single virus, providing a “one drug-one bug” solution. However, this approach has limited efficacy, particularly with emerging and re-emerging viruses with no specific, licensed antiviral drug or vaccine.

Since the outbreak of the COVID-19 pandemic, tremendous studies have focused on the effect of some (broad-spectrum) antiviral agents on this emerging virus. The concept of broad-spectrum antivirals refers to the group of drugs with the capability of combating more than one virus rather than “one drug-one bug” agents. This approach may offer a new horizon for the management of emerging viral threats.

Among BSAs, nucleotide and nucleoside analogs target enzymatic functions shared by some viruses, thus, inhibit their replication. An alternative approach of BSA agents is to target host factors commonly required by multiple viral pathogens, on which the viruses intimately rely. For example, anti-malarial agents (chloroquine and hydroxychloroquine) inhibit acidification of endosomes, an essential process for uncoating of some RNA viruses, kinase inhibitors impair intracellular viral trafficking, and statins attenuate replication of some enveloped viruses.

In this review, we will shed light on BSA agents with potential efficacy against SARSCoV- 2 infection. The time-consuming process of new drug development makes repositioning drugs, already approved for use in humans, the only solution to the epidemic of sudden infectious diseases as COVID-19.

PDX Clinical Trial Design in Anti-Cancer Research

Animal models are useful tools for understanding cancer biology and genetics and serve as an essential platform for the preclinical development of anticancer therapeutics. In this context, cancer-bearing patient-derived xenograft (PDX) models, also called cancer avatars, have successfully replaced the traditional cell linederived models in recent years. PDX-based studies are now widely used for preclinical testing of novel treatments as well as tailoring personalized medicine. For anti-cancer research, however, the use of PDX models propagated from a unique patient does not fully represent the true therapeutic efficacy and toxicity of a drug. That is why many studies in this format later failed to show efficacy and safety in human clinical trials. Hence, the concepts of PDX clinical trials and co-clinical trials have gained importance and prospered in recent years. A PDX clinical trial implies investigation on a set of PDXs originated from multiple patients prior to an early phase human trial, whereas a co-clinical trial refers to drug response assays, in parallel and simultaneously with a human clinical trial, on a set of PDX models established from the same clinical trial participants. A carefully designed PDX- /co- clinical trial requires a meticulous calculation of the sample size, enrollment of pathologically and molecularly diverse patients, and selection of suitable endpoints and outcome measures. With a special focus on PDX clinical trial design in anti-cancer research, this chapter specifically addresses how to develop cancer-bearing PDX models, what to consider in characterizing them, how to track their fidelity to the parental tumor, how to estimate the number of animals included in a PDX trial, how to achieve greater power in the translation of final outcomes, what are the minimum endpoints to be considered, and what measures are preferred for evaluating the response to therapeutic interventions.

Chimeric Antigen Receptor (CAR) T Cell for Pediatric Solid Tumors: The Next Frontier in Cancer Treatment

Combiningthe advancements in genetic engineering technologies and the principle knowledge of cancer immunology, chimeric antigen receptor (CAR) T cell therapy has emerged as a promising therapeutic modality for cancers. The function of CARs is to redirect the immune response to attack cancer cells in a specific manner. Up to date, multiple CAR configurations have been designed to ensure safety and to enhance in vivo persistence and therapeutic potency. A number of clinical trials of CAR T therapy for pediatric solid tumors are underway, mainly focusing on neuroblastoma patients. Although CAR T therapy has been approved by the US Food and Drug Administration (FDA) for hematological malignancies, disappointing response rates have been reported in solid cancers due to several hindrances. Proper target antigen selection, inefficient T cell trafficking, and the immunosuppressive nature of the tumor microenvironment (TME) are the main factors limiting CAR T function. In order for CAR T therapy to become successful in this matter, these challenges must be addressed. The future of CAR T therapy is moving toward the development of the “off-the-shelf” universal CAR T product in the hope of providing cancer treatment to a large population. This chapter reviews the principles of CAR design, current clinical trials, limitations, and future prospects of CAR T cells for pediatric solid tumors.

Plant Molecular Farming for Human Therapeutics: Recent Advances and Future Prospects

Plant molecular farming (PMF) aims to develop plants that express and accumulate proteins of our interest in considerable quantities. Transgenic plants produce edible vaccines, antibodies, therapeutic proteins for human and animal health, and other recombinant proteins required for industrial purposes. Plant systems (PS) to produce pharmaceutical products are preferred over microbial and mammalian systems as they require less input to grow and produce higher biomass. Hence, a variety of proteins are synthesized by plants that are completely free from human pathogens and mammalian toxins. Additionally, they have immunity against infectious and other lifethreatening diseases such as cancer. In this review, plant-inferred therapeutic and nontherapeutic protein items that are in the position of clinical progression or commercialization are summarized. Available plant production platforms are also compared along with associated biosafety and regulatory issues. Further, plant transformation techniques are also analyzed for the development of genetically modified organisms in vaccine production. The use of PMF on a commercial scale is still a long way to go before it is achievable. New methods and techniques are needed to be developed to solve the problems of low yield, scalability, stability, and efficacy of the recombinant proteins, as well as biosafety and regulatory issues. Hence, this strategy will be the ultimate proposed solution to protect humans and animals from health threats in the future.

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.

Tau-Targeted Therapy in Alzheimer's Disease - History and Current State

The two main histopathological hallmarks still required for the diagnosis of Alzheimer's disease are the presence of amyloid plaques and intraneuronal neurofibrillary tangles formed mainly of tau protein. Normally, tau protein regulates intracellular trafficking and provides microtubule stability. However, in AD as well as in other tauopathies, there is a disruption in the normal function of tau, leading to the development of neurofibrillary tangles with disease-dependent ultrastructure of the tau filaments.

After several failures of trials with drugs trying to prevent the accumulation of amyloid, tau protein became another target of molecules designed to modify the course of AD.

Each stage in the development of tau pathology, from the expression of tau protein to its post-translational modifications, with the protein’s aggregation and impaired clearance, presents opportunities for therapeutic intervention: reducing tau expression with antisense oligonucleotides, reducing tau phosphorylation with kinase inhibitors, inhibiting tau acetylation, tau deglycosylation, tau aggregation, modulating tau degradation, stabilizing the microtubules, as well as active or passive anti-tau immunotherapies (with various monoclonal antibodies), have been attempted or are still in trials, with rather inconclusive results so far. It appears that an efficient diseasemodifying therapy is not yet available. Given the complex pathophysiology of Alzheimer’s disease, most likely, a multi-targeted approach would be more effective.

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.

Breast Surgery

At the end of week 4 of human embryonic development, paired thickenings appear in the ectoderm on the ventral aspect of the torso. Extending from the axilla to the inguinal region, they form the mammary ridges or “milk lines.” Subsequently they regress and leave a pair of primary mammary buds at the level of the fourth and fifth inter- costal spaces. The primary buds thicken into lens-shaped mammary placodes. Epithelial cells invade the underlying mesenchyme during weeks 7 and 8 to form the primitive mammary disk. In week 9, a surge of mesenchymal proliferation occurs, coincident with a thinning of the overlying epithelium. A dense mesenchymal stroma then coalesces around the bud. Between weeks 10 and 12, epithelial buds form, begin to branch, and extend into the epithelial–mesenchyme bound- ary. By the first half of the second trimester (weeks 13–20), there are 15–20 solid epithelial cords that converge at the nipples. Ramification processes continue to week 32, when the cords undergo apoptosis to establish tubules and alveoli. At birth, male and female mammary glands are equally formed. There are 20 lactiferous ducts draining into the dimple. In later stages of the final trimester, the mesoderm underlying the dimple changes it into a true nipple with an areola. Placental estrogens during the final weeks of gestation cause breast buds to enlarge to create a true breast nodule at birth, about 1 cm in size, in both genders.

Abdomen

In this chapter we discuss common and unusual conditions of the abdomen that are treated surgically, related to the stomach, small intestine and colon. Such as Hypertrophic pyloric stenosis, is one of the most common surgical conditions of the newborn. Congenital intestinal obstruction occurs in approximately 1 in 2000 live births and is a common cause of admission to a neonatal surgical unit. Normal rotation of the intestine requires transformation from a simple, straight alimentary tube into the mature fixed and folded configuration normally present at birth. Through precise embryologic events, the duodenojejunal junction become fixed in the left upper abdomen while the cecum is anchored in the right lower quadrant. The midgut, defined as the portion of the intestine supplied by the superior mesenteric artery (SMA), is thus suspended from a wide mesenteric base.

Thoracic Surgery

This chapter will include the most common cases of thoracic surgery in the pediatric age group, it ranges from congenital such as diaphragmatic hernia, lung emphysema to acquired conditions such as corrosive injury.Usually two types of deformities considered as Congenital are found to be associated with the chest wall. One may cause depression or protuberance due to overgrowth of the cartilages and the other one causing aplasia or dysplasia. Pectus carinatum (PC), is a protuberance of chest all which makes up to 10% of the chest wall abnormalities while combined PE/ PC makes up 5%, while Pectus excavatum (PE) cause a depression in the chest, thus may be called as sunken, or funnel chest. Jeune syndrome is another syndrome that may exhibit mixed features of PE/PC but is rarely found.

Physiology of the Newborn

The survival of the neonates is dependent on the physiological characteristics that enable them to adapt themselves initially to the placenta and then to the extra uterine environment. Of all the pediatric patients, neonates exhibit the most distinguishing physiological features that ensure their rapid development. This chapter focuses on the physiological characteristics exhibited by the neonates in the intrauterine as well as the extra uterine environment.

Stem Cell Therapy for COVID-19

Stem cells have long been a topic of interest around the globe. Now and then, stem cells are being studied for revealing their beneficial effects. Countries around the world are in a race in stem cell research. Stem cells possess some unique and considerable qualities that hardly any other cell to date has. The outbreak of novel coronavirus or coronavirus disease-19 (COVID-19) was located in Wuhan, China. After a few months, the episode was declared Pandemic by the World Health Organization (WHO) as it engulfed many countries worldwide. Since then, stem cells have gained more push in clinical as well as pre-clinical stage research studies. COVID-19 shares some molecular properties with other coronaviruses like severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). Stem cells surprisingly showed some good outcomes in many patients infected with COVID-19. A lot of laboratory evaluation is being carried out to check the feasibility of different stem cells to be used in COVID-19 infected patients. This chapter discusses and highlights the possible interventions in COVID-19 using different lineages and bio-cultured stem cells.

Key Proteins and Their Roles in COVID-19

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a novel member of the Coronaviridae family that is the causative agent of coronavirus disease- 19 (COVID-19), which is now pandemic in the world. Various proteins characteristically responsible for pathogenesis are categorized as structural proteins (S, M, E, and N), non-structural proteins, and accessory proteins (ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10). Substitution of 380 amino acids and mutations in SARSCoV- 2 compared to other SARS-like coronaviruses characteristically plays a key role in entering the development of infection. S1/S2 of S protein has a specific differential role in SARS-CoV-2 stabilization and resultant infection. In addition to these key proteins, the host and virus-related proteins play risk factors in the spread of this disease. The current chapter will describe the structure of key proteins, their role in pathogenesis, starting from viral attachment leading to the infection in the host compared to the viruses belonging to Betacoronaviruses.

Different Cell Lines for SARS-CoV-2

The recent emergence of the novel betacoronavirus, pathogenic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) with high nucleotide identity to SARS-CoV represents the causative agent of a potentially deadly disease coronavirus disease-19 (COVID-19) in Wuhan, China, and spreading across several countries globally pose a great global public health concern. Until a vaccine is available, effective therapy must be identified, and many clinical trialshave been executed worldwide. Various in vitro investigations are ongoing using different cell cultures to find alternative treatment options, allowing SARS-CoV-2 replications. Various cell lines are susceptible to the SARS-CoV-2 infection. In this chapter, literature regarding SARS-CoV-2 isolated in several cell lines commonly used for diagnostic or research purposes has been summarized. It also shows that SARS-CoV-2 can achieve high titers in various cell cultures derived from different species. In addition, these cell lines are extensively used in the diagnosis, to study pathophysiology, genome studies, and the finding of new targets for drug development and provide new ideas for the discovery of lead compounds with potential therapeutic agents against novel COVID-19.

Indications and Outcomes with Endoscopic Posterior Cervical Rhizotomy

Axial neck pain without much radicular shoulder arm pain is a somewhat tricky situation for spine care providers. Patients often have the early-stage degenerative disease of the cervical intervertebral disc and facet joints, with minimal spinal alignment changes and without instability. Yet such patients may have legitimate symptoms and may have failed multiple rounds of physical therapy, spinal injections, activity modifications, non-steroidal anti-inflammatories, and other medical and supportive care measures. These patients may not fit traditional image-based spinal care protocols and are mostly left untreated. This chapter presents the authors' indications, and clinical outcomes with an endoscopically visualized combined mechanical and radiofrequency facet ablation with a minimal laminotomy at the symptomatic levels. They offer their rationale behind their strategies to attend to these patients with minimal cervical spine disease on advanced images but with unmanageable complaints who ordinarily have been falling into this watershed area of traditional spine care and reviewing possible pain relief mechanisms. The latter may be achieved not only by the combined mechanical and radiofrequency ablation of the cervical facet joint complex but also rely on modulation of the activity of the dorsal root ganglion of the cervical nerve root at the affected level. Outcomes are favorable in most patients, suggesting the authors' approach to treating these patients has merits; thus, warranting further clinical validation.

The Possibilities of Safe Lithium Therapy in the Treatment of Neurological and Psychoemotional Disorders

Lithium is a type of psychotropic drug, belonging to the normothymics classification group. It is used in the treatment of affective disorders such as manic and hypomanic phases of bipolar disorder and severe and treatment-resistant depression. It also has anti-suicidal properties and a neuroprotective effect on neurodegenerative diseases. This article presents findings regarding the effects of lithium in experimental pathology of the central nervous system in mice and rats. In clinical practice, lithium is the standard for pharmacological treatment of bipolar disorders. The drug is also effective in treating depression. It suppresses aggressiveness and is a therapeutic agent in the treatment of chronic neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease. Lithium salts however can be highly toxic even in relatively low doses. The mechanism of action of lithium salts can be realized through the inhibition of glycogen synthase kinase -3β (GSK-3β) and inositol monophosphatase 1 (IMAP1). Inhibition of GSK-3β is considered to be one of the fundamental mechanisms in the implementation of the action of lithium ions on the body. Lithium stabilizes adenylate cyclase activity and acts as an antagonist of sodium ions in nerve and muscle cells. One of the ways to deliver lithium to target organs is to combine lithium salts with a sorbent (a solid porous carrier). This approach made it possible to create modified sorbents for the prolonged delivery of components such as lithium and silver. A new drug – a complex of lithium citrate and a sorbent – aluminum oxide and polydimethylsiloxane (lithium complex) was created at the Research Institute of Clinical and Experimental Lymphology – a branch of the Institute of Cytology and Genetics SB RAS. Its anxiolytic and adaptogenic effects were observed over the course of preclinical studies. The lithium complex improved cognitive functions in experimental animals, influenced the electrophysiological activity of the brain and had positive effects on the behavior of mice in the experimental model of chronic social stress. The lithium complex is therefore a promising drug for the treatment of neurological and psychoemotional disorders.

Foods For Diabetics

The chapter deals with diabetes overview, focuses on the relation of diet and diabetes, the conventional and non-conventional raw material for the development of foods for the diabetic. The chapter also discusses natural and synthetic sweeteners’ overview. Dietary approaches to produce food for diabetic consumers also are addressed, with special emphasis on foods with insulin-secreting, insulin-sensitizing, and insulin-mimetic properties. Also, the terms: glycemic index, insulin index, and glycemic load are defined. And finally, some recipes for diabetic consumers are recommended.

Pathophysiology

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the novel coronavirus disease 2019. This novel Covid-19 has created a serious public health crisis throughout the world. The primary symptoms of coronavirus infection are common cold and influenza-like illness and with time it causes pneumonia. Although various studies are going on throughout the world, its actual pathophysiology is not very well clear to date. The Coronavirus is a positively charged single-stranded RNA virus. This virus gets easily transmitted from human to human. Numerous investigations have been found that the virus enters into the human body via its spike (S) proteins. The S-protein binds to ACE2 receptors and silently comes in contact with alveoli via blood. This entry hypersensitizes various receptors, epithelial cells, macrophages, T-cells, dendritic cells and thus implants proinflammatory cytokines and chemokines, resulting in stressful conditions. Studies found that Hemagglutinin-Esterase protein, Spike protein, Nucleocapsid protein, small envelope protein, internal proteins, group-specific proteins take part in viral pathogenesis, whereas, replication proteins (eIF4A, Cyclophilin, 3CLpro, RdRp) participates in Coronaviruses (CoVs) replication and translation phases, influencing both pathogenesis and pathophysiological conditions. In this chapter, we elaborate on viral pathogenesis, the various functions of proteins, structural, enzymatic, and accessory that are linked with the pathological conditions and will also highlight the correlation causing physiological alteration associated with this infection.

Signal Transduction Pathways Activated During Plant Resistance to Pathogens

The signaling pathways play an indispensable role and act as a connecting link between recognizing the stress molecules and generating an appropriate physiological and biochemical response. Recent studies using genomics and proteomics approach enabled decoding and understanding these signaling networks, which increased our knowledge regarding signaling pathways. This chapter offers a review of the most important bases of plant signaling pathways during various stresses.

Pathologies of the Peritoneum, Mesentery and Diaphragm

Pathologies of the peritoneum, mesentery and diaphragm are uncommon, making their diagnosis more challenging. We present the main issues in diagnosis and treatment. Peritonitis represents acute inflammation of the peritoneum that can be caused by perforation, inflammation or gangrene of an intra- or retroperitoneal structure. The most frequently encountered peritoneal tumours are metastases originating in gastrointestinal, ovarian, lung, pancreatic and breast adenocarcinomas. Lymphomas can primarily or secondary affect the peritoneum. There are two main categories of diseases affecting the mesentery: diseases that start from the mesentery (which can also affect neighbouring organs) and diseases that originate in neighbouring organs. The most encountered hernias of the diaphragm are those occurring through the oesophageal hiatus, but there can also be congenital hernias (oesophageal, Morgagni and Bochdalek) or through post-traumatic defects. As in all other organs, primary diaphragmatic tumours can be classified as benign (cyst and lipomas) or malignant (rhabdomyosarcoma and fibrosarcoma), with other types of primary tumours than those aforementioned being very rarely seen.

Management of Severe Acute Pancreatitis

One of the most important gastroenterological emergencies is acute pancreatitis. It is classified into mild, moderately severe, and severe pancreatitis depending on occurring complications. Establishing etiology and assessing disease severity is the first step of the management. Severe pancreatitis is encountered in 25% of patients and carries the highest mortality. The therapy in these cases is structured on 4 interventions: fluid resuscitation, nutritional support, pain management, specific measures addressed to etiology or complications. Fluid resuscitation for prevention of necrotizing pancreatitis is the foundation of early management. Quality of life in these patients relies on prompt pain management. Early enteral nutrition might reduce mortality, multiple organ failure and infection rate when compared to late enteral nutrition and parenteral nutrition. Pseudocysts and infected necrosis can complicate severe pancreatitis. These symptomatic patients will need appropriate interventional maneuvers depending on imaging and disease extension. Antibiotics should only be given when infection is highly suspected, particularly when necrotizing pancreatitis is involved. Percutaneous drainage is recommended when the collected necrosis has less than 1 month from constitution. In walled-off pancreatic necrosis, endoscopic drainage and subsequent necrosectomy is preferred to percutaneous drainage. Surgery has to be taken into account after failure of endoscopical/percutaneous procedures, intra-abdominal compartment syndrome, or acute on-going bleeding.

Regression and Relapse

Immediately after leprosy treatment initiation, changes in leprosy lesions also commence. The histopathological and bacilloscopic characteristics of the regressing lesions undergo continuous changes over years or decades. It is important to recognize these changes as they allow for the assessment of whether a particular lesion is in regression or if there are signs of disease reactivation. Interpretation of the findings will depend on a close correlation among histopathological patterns, bacilloscopic characteristics, and clinical data. This chapter discusses the main factors that allow the recognition of the histopathological characteristics of regressive phenomena from initial phases to late or residual phases, the changes typical in regressive leprosy granulomas and their importance for assessing treatment effectiveness, the reaction phenomena triggered after treatment initiation on regressing lesions, and the evaluation of leprosy recurrence. Further, this chapter includes a discussion on the main differential diagnoses of leprosy regression and relapse.

Maintenance of Body Composition

Cell, Plasma Membrane, Membrane Transport

Morphology, Genomic Organization, Proteins and Replication of SARS-CoV-2

The current pandemic disease (COVID-19) is caused by a highly infectious coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-Co- -2). It belongs to the family of Coronaviridae, subfamily Orthocoronaa-virinae, order Nidovirales. Coronaviruses (CoVs) are enveloped and spherical shaped pathogens with crown-like protrusions formed by S protein on the surface. The CoVs contain singlestranded positive-sense RNA with genome of 27-32 kb that encodes both structural and non-structural proteins. The Coronavirus genome encodes for at least 6 ORFs, among which two third parts include ORF 1a/1b, which encodes 16 non-structural proteins (nsp 1-16) that play a pivotal role in viral genome replication. The structural proteins are part of mature virion and include spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. The S protein binds to the receptor (ACE2 or others) on the host cell and determines host tropism. Replication of CoVs is extremely complicated process and includes regulation at various stages including dependency on both the viral and host factors. The present chapter provides updated information about the morphology, genomic structure, properties and function of different proteins and their role in replication mechanism of SARS-CoV-2. The information about the proteins and their role in viral life cycle is likely to assist in the formulation of targeted therapeutic interventions and vaccines against this emerging respiratory pathogen.

Functional Annotation and Enrichment of Microbial Proteins Using Systems Biology: Tools and Applications

Genomics and proteomics methods have witnessed a huge surge in the recent decade. Provided the pace of data accumulation from several advanced technologies such as next-generation sequencing, transcriptomics, ChipSeq and quantitative proteomics, the parallel growth in the functional annotation is relatively slow and needs continuous curation and analysis of existed data from repositories. Nevertheless, the standard procedures of functional annotations of proteins which were based on classical data sets, need to be revised in light of advanced and more comprehensive data. In fact, most omics technologies are now integrating and their merger can provide a much realistic and holistic picture of any biochemical and molecular scenario provided the data handling and curation is performed on cellular and molecular principles. A number of genomes and proteomes have been functionally annotated in the past; microbial genomes offer a better opportunity with less complex models. Nevertheless, microbes are among one of the most common causatives of pathogenic diseases and their diagnosis, treatment is limited by available information of proteins and their functions. Previously annotated hypothetical functions to proteins are likely to change in some cases therefore a number of research groups have attempted to re-annotate the microbial genomes with newer data-sets and new tools. Re-annotation of Mycobacterium tuberculosis was one such example. Besides pathogenic microbes, emerging trends in various useful microbes sequencing have shown a tremendous increase in information on human microflora and remain a highly prospective area in biology. Systems biology lies at the interphase of biology, mathematics and computational biology and involves a holistic approach to visualize a biological phenomenon. This chapter describes the basic principles involved in the functional annotation of hypothetical proteins in light of emerging datasets and tools. Besides the suggestions on improving standard pipelines, it also presents a summary of recently annotated microbial genomes and future prospects of involving systems biology in the functional annotation for improved quality and output.

Hormones Management as Anticancer Treatment and Protection: Functions and Mechanism of Action

The available therapy for cancers mostly revolves around chemotherapy, radiation, immunotherapy, and surgery, but these treatment modalities are not satisfactorily treating the patients and are associated with various side effects, pain, immune reduction, trauma, and also induce drug resistance in some patients. Besides, these treatments do not treat the disease's origin but eliminate the tumor itself somewhat without confirmation of avoiding its metastasis. Therefore, there is a need to develop a new effective therapy to treat cancer patients successfully. Hormones naturally present in the human body for controlling various biological and physiological functions also possess potential capabilities to treat different types of cancers. Both preclinical and clinical data show that hormones include anticancer abilities, are controlled by hormonal managing. This chapter has discussed the cellular and molecular role of different types of hormones in treating various kinds of cancers and other pertinent topics related to their impact on stem cell functionality and cancer management.

Meta-inflammation, Obesity and Cardiometabolic Syndrome

The pathophysiological consequences of obesity are largely based on morphofunctional changes in visceral adipose tissue. By disrupting all phases of adipogenesis, visceral obesity causes adipocyte dysfunction with changes in the adipokine secretion pattern and the onset of local low-grade chronic inflammation or meta-inflammation. Anatomical position of visceral adipose tissue allows direct drainage of proinflammatory and prothrombotic adipocytokines into the portal bloodstream and liver, which play a key role in the pathogenesis of insulin resistance, metabolic and cardiovascular disorders, forming a complex cardiometabolic syndrome. The emergence of insulin resistance followed by atherogenic dyslipidemia results in an increase in extracellular concentrations of free fatty acids and the expansion of ectopic fat depots primarily in the liver, pancreas, heart, kidneys, skeletal muscles and bones. Large insulin-resistant fat cells of ectopic fat depots contribute to the development of insulin resistance and low-grade systemic inflammation by endocrine, paracrine, and autocrine secretion of proinflammatory molecules such as: interleukin- (IL) - 6, tumor necrosis factor-alpha (TNF-α), IL-8, IL-1, and others, causing a complex clinical disorder which yields a number of interrelated risk factors and long-term cardiometabolic disease risk increase.

A Review of the Knowledge, Attitude, and Practices of Healthcare Wastes Workers (HCWS) on Medical Waste in Developing Countries

Medical care activities can produce various types of risks (hazardous) wastes. Poor management of these wastes can lead to environmental pollution and health risks to healthcare personnel, patients, and the community at large. Adequate knowledge, attitudes, and practices of managing medical waste are vital. This paper reviews the main issues in medical waste management by healthcare workers in developing countries. Results from reviewed literature showed that in developing countries, Medical waste management is inefficient. Knowledge and awareness concerning safe medical waste management are inadequate as a result of lack of or absence of training for medical waste management personnel, absence of waste management and disposal systems, lack of safety equipment and immunization in most of the health centers. This paper concludes by recommending ways by which poor medical waste management can be ameliorated in healthcare centers.

Induction and Activation of Intracellular Antimicrobial Molecules for Mycobacterial Control

The primary function of antimicrobial molecules is the interaction with pathogens to clear infections. In this chapter, we discuss the role that antimicrobial peptides (AMPs), nitric oxide (NO), and reactive oxygen species (ROS) play in the elimination of intracellular bacteria and their induction by immunomodulators like vitamin D, focusing on the mycobacterial infection. AMPs are the major mechanisms to directly eliminate intracellular bacteria such as Mycobacterium tuberculosis or Salmonella sp. Cathelicidins (LL-37) and β-defensins (HBD-2) are the most studied AMPs, due to their relevance in the immunopathogenesis of several infectious diseases. Additionally, the production of ROS also kills intracellular bacteria directly, especially within the phagosome; patients with ROS deficiencies are susceptible to tuberculous mycobacterial infections. However, excessive production of ROS might induce cell death by apoptosis. The active form of vitamin D (1α,25(OH)2D3) is a key inducer of antimicrobial mechanisms. Vitamin D is involved in redox homeostasis, regulating the effect of ROS and NO to protect the cell integrity; and as an activator of anti-infective pathways for pathogen elimination through induction of AMPs and autophagy. The ability of induction of antimicrobial mechanisms confers these molecules a potential use as adjunct therapies in several infections.

Diagnostics for Neurodegenerative Disorders

Neurodegenerative diseases (NDDs) stem from the loss of neurons and related progressive disruption of psychological, cognitive, and motor functions. The development of NDDs results from either disruption or dysfunction of normal nervous tissues or the accumulation of pathologically altered proteins in the brain. Traditionally, the diagnoses are based on clinical presentations, with limited sensitivity for early diagnosis and specificity for differential diagnosis. However, advancements in the research of biomarkers and biosensing techniques have led to additional promising strategies for the molecular diagnosis of NDDs.

In this chapter, we have reviewed the clinical features, diagnostic criteria and known genetic and protein biomarkers of common NDDs. We have also discussed the importance of bioenergetics in the development of NDDs. Finally, we have placed emphasis on current developments in the detection and diagnosis of NDDs, including neuroimaging, metabolome profiling, and biosensors for NDD biomarkers. Biosensing provides a noninvasive way to diagnose NDDs at an early stage to detect alterations and abnormal products in the blood and brain tissues with high sensitivity and selectivity. This chapter is expected to provide an overview of the recent advances in diagnosing NDDs, as well as pointing out the current progress and challenges in the evaluation and treatment of NDDs and beyond.

Biomarkers and Applications in Alzheimer’s Disease

In this chapter, we will review some methods and platforms related to the diagnosis of Alzheimer’s disease (AD). The global prevalence of dementia and AD shows the urgent requirement of effective treatment, where an accurate and early diagnosis plays an important role. Apart from cognitive diagnosis that clarifies the cognitive deterioration of AD, abundant clinical studies have consistently recognised the core neuropathological features and related fluid biomarkers as utile indicators for the diagnosis and prognosis of AD and its preclinical stages. In order to enhance the accuracy of detecting these biomarkers, convinced methods and platforms are essential. Here, we summarised associated platforms, including imaging platforms (e.g., positron emission tomography (PET) and structural imaging), enzyme-linked immunosorbent assays (ELISA), and matrix-assisted laser desorption/ionisation – time of flight – mass spectrometry (MALDI-TOF-MS).

Natural Products for the Management of Cardiovascular Diseases

Cardiovascular diseases constitute a serious public health problem. It is estimated that they are responsible for nearly 30% of world mortality. Regardless of the developments in the diagnosis and management of cardiovascular diseases, their incidence rate remains increasing. Therefore, newlines of drugs are needed to manage the expanding population of patients with cardiovascular diseases. Even though the most common existing treatments for cardiovascular diseases are synthetic molecules, natural compounds, of different chemical classes, are also being tested. Medicinal plants have been employed in the treatment of some cardiovascular diseases such as congestive heart failure and hypertension many centuries ago. Recently, the traditional remedies application for the treatment of different disorders is gaining revived popularity. In this chapter, we will investigate the efficacy and safety of natural products under preclinical studies and clinical trials with particular emphasis on their traditional uses and implementations in the primary health care system. The great potential of medicinal plants and herbs will be discussed in light of the rising prevalence of cardiovascular diseases as one of the most devastating global health problems.

Antimicrobial Immunoglobulin Prophylaxis and Therapy

Immunoglobulins, either natural or induced, represent powerful means for eliminating microbial threats. For decades, vaccines have been used which function by inducing antibodies for the successful elimination of microbes, preventing disease and mortality.

Polyclonal immunoglobulin products from human plasma were used for the first time to treat immune deficiency during the 1950s. Nowadays, the administration of immunoglobulin, either intravenous or subcutaneous, is the cornerstone of the treatment of primary immunodeficiency affecting the humoral immune system. The therapy can help people with weakened or underdeveloped immune system fight off infections. This is also the treatment of choice for certain autoimmune and neurological diseases.

The polyclonal antibody preparation consists of both natural antibodies and antigeninduced antibodies and reflects the history of antigen experience of the donor population. Natural antibodies are germline-encoded, polyspecific, low-affinity antibodies that also have a regulatory role in maintaining the immune system homeostasis. Antibody preparations, enriched for certain desired specificities, or hyperimmune human globulins are used for prophylaxis and treatment of infectious diseases with a high mortality rate.

It was shown that lymphocytes from survivors of viral infections, without available vaccines, could be used for protective monoclonal antibodies production. This chapter provides insight into the current knowledge of the usage of antibody preparations, efficacy and mechanism of action, with respect to specific diseases, including the treatment of infectious diseases and future prospects.

Subject Index

Utero-Placental Circulation Development

With increasing obesity and diabetes in our population, and alcohol, marijuana, and tobacco use among women of child-bearing years, there is a high probability of embryonic exposure to risk factors before pregnancy is recognized. These metabolic changes and environmental factors are known in animals to induce birth defects and specifically, congenital heart defects (CHDs). This study discusses an interrelationship between placental and heart development in which blood flow between these developing organs needs to be maintained at specific levels. When blood flow is altered in the mouse by embryonic exposure to environmental factors, dysmorphogenesis occurs. Additionally, with gene expression analysis of the embryonic heart it was demonstrated that with elevated homocysteine (HCy) a natural metabolite, and alcohol exposures, numerous Gene Ontology classifications relating to lipid metabolism were altered. As for example, relative to the female embryo, significantly more alterations occurred in the male embryonic heart transcriptome with homocysteine exposure. That lipid metabolism was altered was validated by staining for localization of neutral lipids in the embryonic mouse embryos. We demonstrated that lipid droplet amount and the localization patterning were changed with exposures in both the fetal four-chambered heart and in the placenta. More changes occurred, however, in the placental tissue. We have demonstrated that a regimen of high folic acid supplementation of the pregnant mouse diet started with the morning after conception prevented the environmentally induced alterations. The importance of lipids in trophoblast and placental development, the relationship to gender, and how folate supplementation normalizes development through epigenetic programming is reviewed.

Chemometrics as a Powerful and Complementary Tool for Mass Spectrometry Applications in Life Sciences

Because of its unique capabilities, mass spectrometry is an indispensable part of life science research. In this chapter, a review is made on aids of chemometrics in life sciences applications of mass spectrometry. Because of the increasing complexity of biological samples and ongoing technological enhancements of mass spectrometers, huge sum of data are provided for each biological sample. If the routine exploratory tools are used for data exploration, much of the information is not extractable and hence it gets lost. However, chemometrics helps to explore data thoroughly and extract maximum amount of information. The most common aids of chemometrics in bio-based mass spectrometry data is for experimental design, noise reduction, classification, library search, identification of biomolecules, finding the biomarkers, data compression and data mining.

This chapter is focused on the different aspects of using chemometrics for the analysis of mass spectrometry data in omics and biomedical images. In the first part, chemometrics applications for mass data in omics sciences (metabolomics and proteomics) are revealed. The mass data in omics are mainly provided by hyphenation of mass spectrometry with chromatographic techniques, i.e., gas chromatography (GC), liquid chromatography (LC) and electrophoretic techniques. In the second part of the chapter, the benefits of using chemometrics for mass spectrometry images are revealed. The data of these images are gathered by mass spectrometer itself or hyphenation with chromatographic techniques. Since, hyphenated methods are used for both omics and biomedical imaging, some of the chemometrics methodologies used in these two disciplines may be the same.

The Data Processing Technology of Intelligent Instruments

In this chapter, we will discuss the measurement uncertainty in intelligent instruments; the data processing algorithms in industrial intelligent instruments; the inverse problem and its processing method; the intelligent computing includes the deep learning and machine learning arithmetic in the intelligent instrument design.

MiRNA Mediated Stem Cell Therapy for Cardiac Arrhythmia

Arrhythmias are electrical disturbances resulting in irregular heartbeats. Multiple ion channels orchestrate the coordinated propagation of electric stimuli within the heart. Dysfunction of the ion channels, which may result from genetic alterations in ion channel genes or their aberrant expression, can render electrical disturbances predisposing to cardiac arrhythmias. MicroRNA (miRNA) is a type of small RNA belonging to non-protein coding RNAs and is involved in RNA interference, thereby functioning as a regulator of gene expression. Recently, the role of miRNA in cardiac conduction diseases, arrhythmogenesis and their therapeutic potential has been implicated. Stem cell therapies for cardiac arrhythmia have attempted to modulate defective ionic currents by delivering engineered cells. The modulation or engineering of stem cells with appropriate miRNAs could improvise stem cell-based therapies for arrhythmia. This chapter would review the role of miRNAs in cardiac rhythmic disorders and its potential in diagnosis and treatment of cardiac arrhythmia.

Genomic Fingerprint of Molecular Mechanisms of Breast Carcinogenesis

Breast cancer in women is the most frequent cancer with the highest mortality worldwide. The risk factor includes aging, family history, genetic predisposition, and hormone factor. In recent years, many new gene signatures have been identified, which have a profound effect on breast cancer initiation and progression. Extensive research has been done in the past five decades in understanding breast cancer biology through genomics and proteomics. All these comprehensive studies from breast cancer patients elucidate heterogeneity of disease as one of the complex problems in its treatment and management. The outburst of molecular information has led to an understanding of the biological diversity of breast cancer. The involvement of various genes at different steps of cancer progression, such as proliferation, evading apoptosis, migration, immunosuppression, and chemoresistance, have been described in this chapter. With the advent of miRNA and splicing factors, new differential regulators of genes have been identified in breast cancer. The breast cancer therapeutic approach can be accomplished by identifying the oncogene and tumor suppressor genes at an early stage of the disease. Elucidation of novel genes in breast cancer will lead to identifying new molecular pathways that may be targeted for its treatment. For the prognostic and diagnostic treatment of breast cancer it is very important to identify newer genomic fingerprints and to develop novel therapeutic targets against them. Our main goal is to make available inclusive understanding of molecular mechanisms and hallmarks of breast carcinogenesis.

Deregulation of Enzymatic Post-Translational Modifications in Breast Cancer

Post-translational modifications (PTMs) regulate vital cellular processes such as signaling, proteasomal mediated degradation of proteins, and transcription. Deregulation of post-translational modifications (PTMs) has been proven to have a strong association with breast cancer development. Aberrant PTMs can promote carcinogenesis by perturbing normal cellular homeostasis. The current literature review showed that breast cancer cells displayed abnormal ubiquitination, glycosylation, phosphorylation, and SUMOylation patterns. Breast cancer cells also exhibited stable modifications in histone proteins and DNA. These epigenetic modifications can directly affect the expression of cell cycle regulators by disrupting the transcriptional state of the genome. The current chapter summarizes the involvement of PTMs in carcinogenesis and the mechanism by which PTMs promote abnormal cell growth. Enzymes responsible for aberrant PTMs could be targeted to reduce the severity of the disease and may improve the prognosis of breast cancer.