Nasopharyngeal Cancer

The Geriatric COVID Patient

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

Subject Index

Utilizing in silico Methods in New Drug Design

The current chapter offers a highly informative and enlightening overview of the practical implementation of molecular docking in the field of biotechnology, with a specific focus on drug discovery for a variety of ailments. Molecular docking, an incredibly powerful computational methodology, has increasingly been utilized as an essential instrument in the elucidation of drug-receptor interactions, providing invaluable insights into the process of designing drugs. This chapter delves into the fundamentals of molecular docking algorithms, offering a comprehensive understanding of their theoretical underpinnings, methodologies, and typical applications. Furthermore, this chapter elaborates on how this method is used to predict the binding affinity and orientation of potential small-molecule therapeutics to their protein targets, emphasizing the crucial role that molecular docking plays in the quest for new medications to treat various diseases. By presenting case studies across a range of diseases, this chapter effectively demonstrates the remarkable versatility of molecular docking in advancing our knowledge of disease pathogenesis and therapeutic interventions. In addition, specific diseases and their corresponding drugs are carefully examined, along with an in-depth review of molecular docking studies performed on these drugs. This detailed exploration serves as a robust foundation for researchers seeking to understand the utility of molecular docking in the development of more effective, targeted therapeutics. This chapter thus positions molecular docking as an indispensable tool in the field of biotechnology, propelling drug discovery into a new era of precision and efficiency. Overall, this chapter presents a comprehensive and informative overview of the diverse applications of molecular docking in biotechnology, providing an essential resource for researchers in the field.

Subject Index

Phyto-nanoformulations for the Treatment of Clinical Diseases

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

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

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

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

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

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

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

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

nanoparticles, carbon nanotubes, polymer nanoparticles, and nanoliposomes and

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

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

phytochemical drugs by increasing their stability, better pharmacokinetics and reducing

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

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

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

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

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

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

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

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

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

several diseases.

Soil Fungi-Medicinal Plants Interaction

Medicinal plants are a natural source of therapeutic compounds and
secondary metabolites; therefore, their demand is increasing day by day. Since the last
thirty decades, their cultivation as well as preservation with the help of biofertilizers or
pesticides is a point of great concern. The rhizosphere is an important area around the
roots. It is a habitat for many kinds of microorganisms like fungi. This soil microbial
performs a variety of beneficial functions for the growth of plants such as nitrogen
fixation, solubilization and removal of toxins. Endophytes are also an important class
of microbial flora that helps in the absorption of water and nutrients for the plant.
Additionally, they also make plants able to cope with environmental stresses. Fungal
endophytes supervise photosynthesis. Certain therapeutically important plants
including licorice and white ginger lily can also perform antimicrobial activity
depending upon the endophytic composition they have. These types of plants having
antimicrobial activity are of great significance as they act as eco-friendly biopesticides.

List of Contributors

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

Biological Functions of d- and f- Block Elements

Biosensors for Protein Bio-Sensing and Detection of Bacteria and Viruses

The concept of a biosensor was first proposed in 1962 by Clark and Lyons, who developed an oxidase enzyme electrode for the detection of glucose. Since then, the development of nanotechnology has prompted biosensors to evolve and become more specialized for a variety of applications. Currently, at the forefront of science, bio-sensing applications combined with nanotechnology have implications for multiple fields, including medicine, biology, environment, drug delivery, and food safety. In recent decades, bacterial and viral diseases have seriously threatened human safety. Prioritizing the rapid detection of outbreaks, which pose a major threat to the healthcare system and could have a catastrophic socioeconomic impact, will help stop them. Scientists are conducting extensive research to develop sensitive diagnostic techniques and effective medicines.

Biomarkers for the Diagnosis and Surveillance of Cancer

Cancer remains one of the leading causes of death worldwide. Cancer management has been a daunting task for both health professionals and patients throughout the journey. Screening of cancer at the right time/stage remains the most critical part of the riddle. Certain molecules that characterize cancer, known as ‘biomarkers,’ come out to be the most useful in this journey. The National Institute of Health defines a biomarker as “a characteristic used to measure and evaluate objectively normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention”. These have proven to be often easily available agents employing minimally invasive methods. Biomarkers have played crucial roles in screening, asymptomatic and early-stage detection, monitoring of the treatment therapy and eventual follow-up to check upon a probable re-lapse or metastasis. A cancer biomarker can be any of the biomolecules such as protein, DNA, RNA, proteoglycans, immunological compounds, salivary biomarkers and endogenous peptides. With the refinement in high-throughput techniques, the list of the types of biomolecules and the number of potential biomarkers is only increasing, with volatile organic compounds from the breath (breath biopsy) adding to the list. In this chapter, we shall put effort into reviewing this otherwise very vast topic. The chapter will outline various types of biomarkers, the journey so far with clinically approved cancer biomarkers, the challenges being faced, and conclude with future perspectives.

Chromosome 19

Gene is considered discrete coding units that contain the information for individual proteins. These lot of genes were combined and named DNA which is tightly coiled many times over the histone protein to form Chromosomes. Humans have got 23pairs of chromosomes, including the sex chromosome. The current study is about the major genes and their functions that are present in chromosome 19. There are approximately 1500 genes present in this chromosome, and changes in chromosome 19 are identified in many cancers. Dislocation of the chromosome, a mutation in genes that are present in a chromosome (rearrangements, deletions, or duplications) of DNA in the chromosome, epigenetic modification, and lifestyle changes are some of the chromosomal abnormalities that are responsible for cancer-causing. These changes will trigger the growth of normal cells and induce cancer cell proliferation, migration, invasion, angiogenesis, and metastasis. The signaling pathways like PI3K/AKT, JAK/STAT, NF-κB, and TGF-β are responsible for the various cellular functions with the result of autocrine, juxtacrine, intracrine, paracrine, or endocrine. When the dysregulation of these signaling pathways leads to cancer progression and metastasis. Prostate cancer, breast cancer, gastric cancer, pancreatic cancer, colon cancer, gastric cancer, lung cancer, leukemia, and cervical cancer are the major cancers that are caused because of mutation that occurs in chromosome 19.

Chromosome 16

Cancer is a heterogeneous disorder with invasive and metastatic potential. It is a deadly disorder affecting 1 in 6 people worldwide. Hence, it is important to eliminate the disease. Genetic alterations remain an underlying cause of cancer, and several gene mutations were involved in causing different types of cancer. Recently, researchers have been investigating the role of genetic mutations in causing cancer. For this reason, the genes associated with chromosome 16 were investigated for their role in causing cancer. This study revealed 70 genes associated with cancer. Of which, the cadherin genes (CDH11, CDH13, and CDH1), AXIN-1, ANKRD11, BANP, CYLD, CBFA2T3, IR8, MVP, MT1F, NQO1 and PYCARD was the tumor suppressor, and the gene MSLN is the potential oncogene. CBFB and MYH11 are well-known fusion genes associated with this chromosome. Loss of heterogeneity was noted in the q arm of this chromosome. The chromosome translocations, t (16;16) (16) (p13q22), t (16;21) (21) (p11;q22), t (12;16) (q13; p13; p11), t(16;21) (p11;q22) and t(7;16) (q33; p11) led to the development of acute myeloid leukemia, leukemia, and sarcoma. Several other genes associated with chromosome 16 responsible for cancer initiation and proliferation are summarized in this chapter. A novel insight into the genetic biomarkers and therapeutic targets has been provided to develop potential therapeutic strategies against cancer.

Subject Index

Chromosome 8

Chromosome 8 spans more than 146 million DNA base pairs, and represents between 4.5 and 5 percent of the total DNA in cells. Sixteen percent of these genes and their mutations have been identified to play a role in cancer development. Cancer is a genetic disease at the somatic cell level. Multiple gene mutations usually precede them throughout one’s life. Oncogenes such as Myc, Lyn, Atad2, etc., from chromosome 8 promoted cancer cell proliferation, invasion, and migration. The increased expression of these proteins can transform a normal cell into a cancer cell. Chromosome 8 also houses multiple tumor suppressor genes, such as Dlc1, E2f5, Gata4, Ido1, etc. These proteins, when expressed, reduce the chances of tumor initiation within cells. Thus, mutations leading to the reduced expression of these genes are associated with multiple cancers. Mutation of other functional genes like Ank1, Ctsb, Ext1, Il7, etc., has also been implicated in various cancers for their role in increasing the invasive nature of cancers by regulating angiogenesis and facilitating cancer metastasis. Cancers can also stem from the translocational mutations of genes in chromosome 8. This chapter explains essential cancer genes, genetic mutations, and gene variations that can cause an increased risk of cancer and its progression.

Chromosome 6

Chromosome 6 is among the 23 pairs of chromosomes in humans and it spans about 170 million base pairs. Several cancer genes have been identified to have a role in cancer development. Cancer is also a genetic disease caused due to changes in the genes that control cell function, such as cell division and cell growth. Most of these cancer genes either act as tumor suppressors or possess an oncogenic potential. Oncogenes like ROS1, MYB, HMGA1, etc., induce tumorigenesis by playing a role in DNA repair, replication, transcriptional regulation, and mRNA splicing. When these genes are highly expressed, they result in the transformation of normal cells to malignant cells; on the other side, tumor suppressor genes like IGF2R, AIM1, IRF4, etc., reduce tumorigenicity and invasive potential. Thus, reduced expression of these genes due to loss of heterozygosity, deletion or any epigenetic modifications can induce tumor formation. Also, some genes can either suppress or induce tumor formation given the cellular location and condition, such as CCN2, TNF, etc. Along with these, different types of structural abnormalities can be observed on chromosome 6, such as chromosomal translocation, deletion, duplication, and inversion. These abnormalities on both p and q arms have been known to contribute to the growth and spread of cancer by impacting the expression of cancer genes. Aberrant expression of the genes can also be influenced by fusions, missense mutations, non-missense mutations, silent mutations, frame-shift deletions, and insertion at the molecular level. Some genes can maintain stem-cell-like properties by regulating the expression of cell surface markers like Oct4, Nanog, Sox4, etc. This chapter explains important cancer genes, genetic mutations, and gene variations that can influence the risk of having cancer and induces cancer formation.

Chromosome 3

Myriad genes in the genome have been implicated in cancer. However, a focused compilation of genes from the same chromosome would provide a valuable detailed yet succinct catalog for researchers, advantageous in quickly understanding the leading roles played by these genes in cancer. This chapter fulfills the above aim of furnishing a pocket dictionary- like a concise yet meticulous explanation of many genes from Chromosome 3, describing these genes’ functional essentialities in various cancers. Such a judicious collection of genes from a single chromosome is probably the first of its kind. The multiple inputs in this chapter from Chromosome 3 include oncogenes (BCL6, RAF1), tumor suppressor genes (SRGAP3, FHIT), transcription factors (FOXP1, MITF), fusion genes (MECOM), and many other types. With approximately 1085 genes spanning 198 million base pairs, Chromosome 3 constitutes 6.5% of the total DNA.

Chromosome 2

The human chromosome 2 was formed by a head-to-head fusion mutation caused by two chromosomes of our ancestors. The gorilla and chimpanzee contain 48 chromosomes in contrast to 46 chromosomes in humans. Ten million years ago, the two chromosomes of apes underwent telomere-to-telomere fusion that gave rise to human chromosome 2. Apart from the exciting history, the human chromosome 2 is involved in various genetic conditions caused due to chromosomal deletions and duplications, leading to SATB2 (Special AT-rich sequence-binding protein 2)-associated syndrome, MBD5 (Methyl-CpG-binding domain 5)-associated neurodevelopmental disorder, 2q37 deletion syndrome, partial trisomy 2, myelodysplastic syndrome as well as cancer. These mutations cause different human abnormalities, such as craniofacial anomalies, cleft palate, genitourinary tract anomalies, microcephaly, hypotonia, heart defects, anemia, and myeloid malignancies. This chapter discusses 50 genes of human chromosome 2 involved in various cancer types.

Mushrooms Against Malignancies: from Chemosensitization to Immunopotentiation

Malignancies have been among the diseases which claim most of the lives around the globe. They also impact the socioeconomic level as well as emotional detriments among the near and dear ones. Various strategies and interventions have been devised to combat these life-threatening conditions. The ill effects associated with synthetic drugs comprising most of the anticancer drugs enforce looking for an alternative source for molecules with therapeutic potential. Mushrooms are one of the most prominent sources of bioactive molecules with diverse medicinal properties. Various mushrooms have shown their ability to inhibit the proliferation of neoplastic cells both in in vitro and in vivo investigations. Mushrooms and their active constituents can affect the various Hallmarks of Cancer. Mushrooms are not only able to inhibit the proliferation of cancer cells, but they also prevent the onset of carcinogenesis. The anti-angiogenic property of various mushrooms is indicated in several research investigations. The immunomodulatory potential and ability to avert metastasis also aid in the anticancer potential of this wonderful food item. Due to the high nutritive values of edible mushrooms, they have been suggested as nutraceuticals and contribute to nutritional management in diseases including cancer. The active constituents are also proven to have chemosensitizing ability. Preventive management of cancer and reverting chemoresistance have been sought as promising achievements in the clinical management of malignant conditions. Moreover, the nutritional values of mushrooms, along with their therapeutic potential at various fronts against cancer, make them a strong candidate for clinical application. This also warrants the careful exploration of mushrooms, their nutritive potential, and bioactive constituents against malignant disorders in laboratory and clinical settings.

Subject Index

Probiotics-based Anticancer Immunity in Head and Neck Cancer

Every day we are used to hearing about cancer and its effects. Head and neck cancer is one of the types of cancer which is leading to mortality. Treatment of cancer is crucial to lead a happy and healthy life. Till today several medical strategies, such as radiotherapy, chemotherapy, etc., have come forward to eradicate cancer, but along with these approaches, probiotics are also taking part to dissolve this problem. In simple words, probiotics are microorganisms that are present in fermented foods like yogurt, cheese, creams, fermented milk, etc., which, when administered to the host, provide health benefits. Some familiar probiotics are Lactobacillus bulgaricus, L. casei and Streptococcus thermophilus, which are involved in cancer treatment. Much evidence has proven its health benefits. This chapter focuses on how probiotics act on cancer cells with an introduction to head and neck cancer, thereby triggering our interest to probe into further research on treating cancer using probiotics.

Pathophysiology of Gastrointestinal Tract Cancers and Therapeutic Status

Cancers of the gastrointestinal tract (GIT) are the most common human malignancies. The prevalence of esophageal Cancer, pancreatic ductal adenocarcinoma, gastric Cancer, hepatocellular carcinoma, colorectal Cancer and gallbladder Cancer are on the rise now a days. Despite advances in cancer treatment, increasing reports are focusing on finding novel therapies with lower side effects and higher potency. From the mechanistic point of view, several dysregulated factors are behind the pathophysiology of GIT cancers. Multiple studies have shown molecular targeted therapies in various GIT cancers, including epidermal growth factor receptor pathway (EGFR), vascular endothelial growth factor pathway (VEGF), Wnt/β-catenin pathway, and insulin-like growth factor receptor (IGFR).The aforementioned mediators are the critical targets of the existence of monoclonal antibodies and small molecules in treating GIT cancers. Accordingly, providing the exact dysregulated mechanisms behind GIT cancers could pave the road in the treatment of cancers. This chapter reveals dysregulated signaling pathways and potential therapeutic agents in the treatment of GIT cancer.

Epigenetic and Genetics Factors

Despite variations in the morphology and behaviors of human body cells, every single cell in our body is composed of identical DNA material. The variation in cell phenotypes is a result of a specific regulatory mechanism known as epigenetics, by which gene expression undergoes some modifications without the actual nucleotide sequence being affected [1]. This phenomenon is accomplished through several mechanisms, such as cytosine residue methylation, modifications of histone units, and RNA interference. Therefore, epigenetics performs a key function in embryonic growth and development, cellular RNA expression, gene imprinting, and silencing of females’ X chromosomes [2]. Any impairment in these mechanisms may cause various human disorders, including cancer [3]. In carcinogenesis, defective epigenetic machinery at several distinct levels results in abnormal cellular functions [4]. This chapter highlights epigenetics' importance in cancer development and its potential applications for cancer treatment.

Growth Factors and Cancer

Cancer causes major patient morbidity and mortality and is a critical health concern worldwide. The recent GLOBOCAN 2019 factsheet recorded nearly 19.2 million new cancer cases, 9.9 million cancer deaths and 50.55 million people suffering from different kinds of cancer globally within 5 years after diagnosis. Growth factors (GF) are a group of proteins that can affect cellular processes, including differentiation, division, intravasation, extravasation and dissemination. The circulating tumor cells in the bloodstream can populate distant tissues and organs and believe to be the primary cause of metastasis. Extravasation is a crucial phase in the metastasis process, in which tumor cells leave the bloodstream and enter the host tissue. The progress of metastasis is triggered by the tendency of cancer cells to disseminate to target organs from the site of the primary tumor. Despite extensive basic scientific and clinical investigations, cancer is still a major clinical and public health problem. The development of cancer can be influenced by genetics, environmental factors, gene-environment interaction, lifestyle, age and a number of other factors. The harnessing and enhancement of the body’s own cytotoxic cells to prevent basement membrane rupture and the intervening dissemination processes can provide useful insight into the development of cancer. The mutation in oncogenes and tumour suppressor genes, and chromosomal aberration is a cornerstones of the molecular basis of cancer. The basement Membrane (BM) acts as a cell invasion shield, thus identification of processes that underlie in breaching of BM can contribute to understanding the disease pathogenesis. TGF-β is known for its dual function; it requires inhibition in the advanced stage however, the growth inhibitory properties are displayed in the early stages of tumorigenesis. Therefore, inhibition of TGF-β signalling in the CD8+ T cell compartment may be necessary for tumor immunity to be restored. Quantitation of tumour cell dissemination is important and plays significant role in elucidating mechanisms of cancer and strategies for therapeutic intervention.

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.

Biosensor Application

In Chapter 5, we want to focus on biosensors application in different fields and Focus on various newest research related to electrochemical biosensors in the fields of medical diagnosis, environmental monitoring, and food quality. In the medical diagnosis section,, the research done on HIV-1 is examined. Then hepatitis B, hepatitis A, Ebola, Zika, murine norovirus, influenza A, dengue serotype 2, adenovirus, enterovirus 71, Epstein-Barr virus, the apple steam pitting virus, papillomavirus, and phinovirus, are examined, respectively. In addition, in the monitoring environment section, research conducted on heavy water and pesticides is reviewed. In the food quality analysis section, research conducted on food toxicity and Antibiotic residues are reviewed.

Current Approaches to Antimicrobial Formulations and their Delivery

With the escalating concerns about antimicrobial resistance and the intractable nature of microbial infections, there is a demand for the expansion and development of alternative stratagems for treating microbial diseases. At present, the advent of antimicrobial resistance amidst microbial pathogens, especially the ‘drugresistant’ ones, has led to poor clinical consequences, thus, shooting up healthcare outlays and mortality. Moreover, the formation of biofilms-like assemblies by microorganisms and their surface association mechanisms have led to secondary infections in immunocompromised individuals and further muddled the prophylaxis. Such microbial resistance is primarily attributed to the inapt and undue use of antimicrobials in humans/animals and the unregulated administration of these drug formulations. Therefore, there is an urgent need to propose and imbibe various modern, multifaceted antimicrobial formulation approaches to prevent the fatal consequences of antibiotic resistance and enhance the effectiveness of microbial growth control. Currently, several new-age antimicrobial formulation therapies are being explored and have shown promising results as efficacious preventatives, diagnostics, and drug carriers in comparison to conventional antibiotic therapy being used. In this chapter, we highlight the different categories of new-age antimicrobial formulation therapies currently in use, their molecular mechanism of microbial targeted delivery, their effectiveness over the traditional therapies, the challenges in their development and the future outcome of these contemporary formulations.

miRNAs as Epigenetic Cancer Biomarker

Despite the fact that the mortality rate of many types of cancer has decreased in the last decades, cancer remains one of the most challenging diseases in the world. The number of newly diagnosed cases with advanced stages in different types of cancer is still high because available tests are not efficient enough to be used for screening. In addition, the available diagnostic tests failed to diagnose certain types of cancer until late presentation. Furthermore, therapeutic agents currently in clinical use to treat a certain type of malignant tumours still show a high rate of resistance in some patients. Many types of available cancer biomarkers failed to manage and resolve this problem because of the lack of both sensitivity and specificity of these markers. Advanced researches in epigenetics highlight the importance of certain non-coding genes in diagnosing and follow-up of patients with different types of cancer. One of these substances is microRNAs (miRNAs) which showed high sensitivity and specificity as cancer biomarkers. miRNAs are highly stable and expressed in different types of human body samples; some of them are tissue specific. These features make them available as cancer biomarkers, and they are started to be in clinical use recently.

Some Aspects of Pathology and Pathogenesis of Coronavirus Infection

This chapter presents an overview of pathology and pathogenesis in coronavirus infections in humans and animals based on literary data and our own experience, illustrated by numerous original images.

The Role of Flavonoids and other Selected (Poly) Phenols in Cancer Prevention and Therapy: A Focus on Epigenetics

The importance of diet in determining the incidence of chronic illnesses such as diabetes, cardiovascular disorders, neurodegenerative diseases, and cancer has inspired extensive research on the role of individual dietary components in chemoprevention. Flavonoids and (poly)phenols have often been identified as the ideal candidates for these types of studies, as they represent large classes of natural products that are widely available in fruit and vegetables. In this chapter, we will discuss the antiproliferative properties of flavonols, flavanols, flavones, isoflavones, anthocyanins, curcuminoids and resveratrol derivatives, with a particular focus on their ability to interfere with epigenetic processes and modulate gene expression. We will look at the challenges encountered during the optimisation of the pharmacokinetic and pharmacodynamic properties of these natural products and, where possible, we will define structure-activity relationships.

Subject Index

Health Effects of Arsenic

Arsenic is a naturally occurring element with exposures in various work settings. Arsenic exposure can occur environmentally, particularly through drinking contaminated water and ingestion of some foods. The most toxic forms are inorganic arsenic, iAs (trivalent, pentavalent), and its metabolites, as well as the highly toxic arsine gas, the latter causing hemolysis. There are also organic arsenicals in food, particularly seafood, of little or no known toxicity. Inorganic arsenic is well absorbed through ingestion and respiration and is quickly cleared from the blood, distributed throughout the body (including across the placenta), metabolized in the liver, and excreted in the urine with metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Most of it is excreted with a half-life of days. Inorganic arsenic disrupts numerous enzyme systems, causes oxidative stress and induces alterations in gene expression. Acute severe poisoning, rarely seen in occupational settings, is life-threatening, usually presenting with gastrointestinal symptoms and severe diarrhea that can progress to cardio-pulmonary collapse, requiring treatment in intensive care, with chelating medication. Chronic iAs exposure can lead to characteristic skin lesions, increased cancer risks (particularly skin, lung, bladder), and other cardiovascular, neurological, endocrine and reproductive adverse health effects. Assessment involves history, physical exam and urine arsenic (can be a spot sample corrected for creatinine), speciating the sample for inorganic species. This urine arsenic biomarker assesses current exposures. Treatment and prevention focus on identifying and eliminating or decreasing exposure, both in the workplace and environment.

Heliotropium, an Ethnomedicinal Plant: Past and Present Uses

The genus Heliotropium is formed of herbaceous plants belonging to the family Boraginaceae. In Chile and around the world, many Heliotropium species are commonly used in traditional and complementary medicine to treat various diseases. Members of this genus are also recognized for unique biosynthesized phytochemicals, mainly terpenoids, phenolics and alkaloids. Due to important phyto-constituents, as well as their therapeutic potential, many Heliotropium species have been subjected to chemical, biological and pharmacological investigations. This review details the many ethnomedicinal uses for Heliotropium, with an emphasis on Chilean species, and analyzes their scientific validation based on the chemical constituents and pharmacological properties of Heliotropium reported in academic publications. In addition, we discuss the critical conclusions, as well as some suggestions for future phytochemical and biological studies with Heliotropium species.

Subject Index

Epidemiology of COVID-19

The epidemiology of COVID-19 infection will be understood by the relationship between the intensity of action on public well-being and the rate of its transmission control. The virus is a chemical substance that is vulnerable until it invades the living body. The molecular assembly of the virus contains RNA genome and proteins. When 2019-nCoV enters the host cell of the living body, it continues its progeny by the replication process. It starts to make molecular assemblies for every new virion produced through replication and transcription. Though the incubation time is accounted for to range between 1 to 14 days, the median incubation period is 5 days. According to a recent survey on COVID-19 patients, 80 percent of patients are asymptomatic. This book chapter describes the life cycle and spread of 2019-nCoV, CFR, clinical manifestations, diagnosis, and prevention of COVID-19.

Mitochondrial Dysfunction and the Immuno-inflammatory Response Induced by SARS-CoV-2 Infection: the Role of Mitochondrial DNA

In 2019, a new coronavirus (SARS-CoV-2) was identified in China and had rapidly spread across the world. Its associated disease, coronavirus disease 2019 (COVID-19), has led to millions of deaths in 2020-2021. Studies have been demonstrating that SARS-CoV-2 induces a systemic hyperinflammatory state, which is associated with a decreased cytotoxic capacity and impaired Type I interferon (IFN) response. Moreover, iron dysfunction/hyperferritinemia in association with hyperinflammation leads to oxidative stress and apoptosis. Altogether, these cellular events contribute to COVID-19 severity. In viral infections, systemic and cellular alterations can promote mitochondrial dysfunction. In this regard, dysfunctional mitochondria can trigger the immune response, leading to the release of mitochondrial damage-associated molecular patterns, including mitochondrial DNA (mtDNA) and reactive oxygen species (mtROS). mtDNA is known to promote a beneficial antiviral response; however, sustained nocive stimuli, such as SARS-CoV-2, could turn this response into oxidative stress and exacerbated inflammation leading to tissue injury. In addition, mtDNA can be released into the extracellular space and induce a proinflammatory state in neighboring cells. Here, we highlight the potential role of mtDNA as an important marker of hyperinflammation in the progress of COVID-19. Furthermore, we briefly discuss the role of mtROS and its interactions with the mitochondrial antiviral signaling (MAVS), which can also contribute to COVID-19 immunopathogenesis.

Heterocyclic Anti-cancer Compounds Derived from Natural Sources with their Mechanism of Action

The variety of natural compounds is indispensable due to their mechanism of action. For many years, natural compounds have been used to develop new classes of chemotherapeutic agents. Chemotherapeutic agents derived and synthesised from natural sources could be the best possible alternatives to minimise the harmful aftereffects of conventionally used agents against cancer, especially oral and maxillofacial carcinoma and tumors. The proposed chapter concentrates on recent research on various classes of natural scaffolds and their analogues that possess potent antitumor activity. Moreover, we would like to provide an analysis of preclinical and/or clinically investigated natural compounds. These compounds and their synthetic heterocyclic analogues were found to be obtained through bioactivity and mechanism of actiondirected isolation and characterization, conjoined with modification using rational drug design-based approaches and analogue synthesis. Structure-activity relationships, structural change, and molecular mechanisms of action will all be examined.

Artificial Intelligence-based Nanosensors to Compose the Patient's Cancer Biomarker Profile

To design biomarker diagnostics, unique characteristics of nanotechnology are utilized. For decades, biomarkers have been used in clinical medicine. The use of such high-sensitivity nanosensors will provide patients with an earlier diagnosis of the disease and make major improvements in clinical outcomes. The biomarker profiles taken from tumor samples of patients and the clinical meta data can provide proficient management of cancer patients having comparable molecular subtypes. Thus, artificial intelligence plays a major role in developing advanced diagnostic tools, such as nanosensors, that focus on identifying the complexity of cancer disease diagnosis, thereby emerging as a valuable cancer research outcome in the public domain. This chapter focuses on nanosensors, highlighting their importance for cancer diagnosis applications.

Anesthesia for Pediatric Patients with Common Comorbidities Part III

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

Subject Index

From Cells to Clinic - Direct Biomolecule Quantification of Clinically Relevant Biomolecules

Translation of investigative cellular analysis into reliable clinical settings is

a challenge and surface enhanced Raman spectroscopic (SERS) technique has the

potential to move beyond laboratorial examinations. Quantitative and qualitative

measurement of cellular components and their properties is essential indicative of

healthy or disease state. Pre-emptive analysis of diseased state offers synchronization

with early diagnosis of certain medical conditions and is requisite for initiation of

therapeutic interventions. High sensitivity and capacity for multiplexing renders SERS

suitable for biochemical analysis for disease diagnosis a critical step towards

formulation of therapeutic regime. SERS assists in a deeper understanding of cellular

processes and its micro environment without disturbing and damaging the cellular

milieu in 3 dimensional (3D) set up without invading the tissues. Fabrication of novel

nanostructures with enhanced plasmonic effects has also propelled the growth of SERS

based analysis of cellular structure in normal and abnormal circumstances. Thus, SERS

is operating as diagnostic tool for in-vitro, ex-vivo and in-vivo investigations for

assessing onset of disease as well as prognosis of the therapy in hospitals and clinics.

COVID-19 Pandemic: A Comprehensive Overview of Epidemiological, Pathogenesis, Diagnostic Aspects and Therapeutic Interventions to Tackle Current Outbreak

Coronavirus disease 2019 has been declared a pandemic globally by WHO after its first emergence in Wuhan city of China. The disease was observed to be caused by SARS-CoV-2 infection. Although a complete spectrum of clinical manifestations linked with COVID-19 is yet to be determined, on the basis of virus evolution and genomic recombination; SARS-CoV-2 is believed to be belonging to the Coronaviridae family with the zoonotic origin, exhibiting several symptoms in human patients ranging from being asymptomatic to severe illness, ultimately leading to high mortality rate. Different molecular, serological, and radiological techniques have been employed to detect SARS-CoV-2 infection. Epidemiological insights have revealed that the infection has threatened the health and economy of all the nations worldwide. Diverse pharmacological interventions are already under place to fight against the current pandemic, and a few of them have already been approved by FDA. Natural products and herbal medicine could also play a prominent role as an alternative therapeutic approach to fight against the current pandemic, and few of their clinical trials have already been registered. The purpose of this chapter is to provide a comprehensive overview of the origin, genomic diversity & evolution, epidemiology, pathogenesis, transmission, diagnosis, possible therapeutic approaches of COVID-19, and experiential learning to enhance our preparedness for upcoming but unknown outbreaks.

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.

Pharmacotherapy of Multiple Sclerosis and Treatment Strategies

Multiple sclerosis (MS) is a well-known chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). It is considered the most common autoimmune demyelinating disease of the CNS. It affects mainly young adult females between 20-40 years of age. MS was previously considered a Tlymphocyte- disease, but now B lymphocytes appeared to have a critical role in MS's pathogenesis. Affected patients showed lower quality of life with an increased death rate than the general population. The treatment of MS is challenging, and many drugs have evolved primarily for the last 20-30 years. Since the introduction of interferons in 1993, there are more than sixteen disease-modifying therapies (DMTs) approved. These drugs have different pharmacologic forms like injections, oral forms, and intravenous infusion drugs. Each one has its benefits and drawbacks. Moreover, like any other patient, MS patient has other symptoms that are not covered by DMT and need symptomatic treatment. In this chapter, we attempt to present medications used to treat acute relapse, different DMTs, symptomatic treatment for different MS symptoms. Besides, we give attention to drugs under clinical trials.

Revaluation of Thyrotropin-Releasing Hormone and Its Mimetics as Candidates for Treating a Wide Range of Neurological and Psychiatric Disorders

Thyrotropin-releasing hormone (TRH) is a neuropeptide having many biological and pharmacological activities. TRH (protirelin tartrate) has been used for the treatment of persistent disturbance of consciousness disorder because of its amelioratory effect. However, therapeutic use of TRH entails problems, such as its low lipophilicity, short half-life times due to specific degradation enzymes, and low penetration of the blood-brain barrier (BBB) for access to the central nervous system (CNS). To overcome such problems, a large number of TRH mimetics have been developed for the treatment of various neurological and psychiatric disorders, including spinocerebellar degeneration (SCD), cognitive impairment, and Alzheimer’s disease (AD), given by non-oral routes such as intravenous (iv) administration. However, orally effective TRH mimetics are needed to help improve the quality of life (QOL) of patients. As the first orally active TRH mimetic for the treatment of SCD, Taltirelin (Ceredist) has been launched in Japan for administration twice a day. Recently, rovatirelin reported to have high oral bioavailability (BA), was developed for SCD as a potentially effective treatment option in clinical trials by oral administration once a day. This would allow treatment with TRH and its mimetics to be moved from the hospital to outpatient or homecare facilities, and their use for a wider range of disorders. In the near future, TRH and its mimetics should become available as one of the key treatments for various neurological and psychiatric conditions, such as AD, Parkinson’s disease (PD), depression and so on.

Immunotherapy Approaches Focusing on Cancer Stem Cells

Metastasis and relapses are still one of the main causes of death in many cancer patients, and they probably occur since cytotoxic chemotherapy as well as the the stress from surgery itself can impair the steady immunological state, the ability to develop an antitumor immune response and also because of poor cancer stem cells (CSC) elimination. CSC appear to use features of both cancer cells and stem cells, including self-renewal and resistance to apoptosis for survival and proliferation, making cancer elimination even more difficult, which then becomes a potential therapeutic target. In this scenario, the successful generation of immunity is the key that can help fight against cancer. Techniques such as monoclonal antibodies, dendritic cell vaccine, and adoptive T cell therapies have been developed, targeting CSC to eliminate tumor mass. In this chapter, some features and aspects of CSC, as well as their relation with patients’ prognosis and therapeutic values, will be listed.

Subject Index

Current Medical Imaging and Artificial Intelligence and its Future

“Artificial intelligence and medical image” is an auxiliary tool for the computer to complete image classification, target detection, image segmentation, and retrieval and assist doctors in diagnosing and treatment based on medical image through deep learning. This chapter includes the review of Artificial intelligence (AI) and its application in radiology, pathology, eye disease, deontology, dermatology, and ophthalmology, which we have benefited from the use of AI methods. Modern medicine is evidence-based medicine based on experiments. Doctors' diagnosis and treatment conclusions must be based on corresponding diagnostic data. Imaging is an important part of diagnosing, and 80% to 90% of data in the medical industry are derived from medical imaging. Therefore, clinicians have a strong demand for images, and they need to conduct a variety of quantitative analyses of medical images and comparison of historical images to complete a diagnosis. In contrast to this qualitative reasoning, AI is good at identifying complex patterns in the data and providing quantitative assessments in an automated manner. Integrating AI into clinical workflows as a tool to assist physicians allows for more accurate and repeatable radiological assessments.

Antitumor Effects of Heparin

Heparin was isolated from the liver and heart in 1916. Heparin was demonstrated as an anticoagulant in the presence of heparin-cofactor, a plasma component. Over years many heparin molecules have been manufactured due to their anti-tumor properties. Heparin sulfate, an essential component of the extracellular matrix when degraded by heparanase secreted by tumor cells has shown to increase tumor invasiveness. The anti-angiogenic properties of heparin are due to its effect on decreasing fibrin level and inhibition of thrombin formation. Natural killer (NK) cells destroy circulating tumor cells. The anti-tumor properties of heparin have been demonstrated in various studies. Among various forms of heparin, butanoylated heparin has the lowest anticoagulation strength but much stronger anti-tumor activity compared with UFH at higher doses. The anti-tumor effects between LMWH and butanoylated heparin are yet to be compared.

Diagnostic Measures for COVID-19: Current Status and Advances

The outbreak of COVID-19 in China and its gradual spread over the entire globe, irrespective of age, sex or origin, has posed a major threat to the health of the entire human population. Investigations subsequent to the virus outbreak revealed that the unknown etiology was a novel coronavirus, later referred to as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatment and survival of patients have been largely dependent on an accurate diagnosis of this infection, both in symptomatic and asymptomatic individuals. Thus, highly sensitive and specific laboratory diagnostic methods are imperative for the accurate diagnosis of this condition. This manuscript focuses on various molecular and diagnostic imaging tools for reliable diagnosis of COVID-19 and the correlation of their outcomes with those from previous coronavirus epidemics. The molecular diagnostic tools include real-time reverse transcription polymerase chain reaction (rRT-PCR), ELISA based detection of early humoral response and DNA sequencing. The manuscript will also focus on national and international policies of testing, additional developments, issues and challenges faced in the diagnosis of COVID-19. The chapter will, therefore, highlight the current regime followed, developments and the probable lacunae that, if overcome, could improve the diagnostic schema of this disease.

Is Our Psychology Affected By the Pandemic? How?

We are facing a de novo global crisis that we have never faced after World War II. During the pandemic period, there is an increased and uncontrollable level of ‘information pollution’ compared to the past, especially in social media and other mass media. This increases the stress load on people. Developing adverse emotional, physical, or cognitive responses that arise in response to the effects of the COVID-19 pandemic is viewed as a normal reaction to one’s environment. Anxiety, depression, and delirium can ensue as a pathological and extreme persistent response to these stimuli. During the pandemic period, it is normal to feel down as you get information about it. In fact, worrying during this process is a necessary reaction to protect ourselves and is a normal emotional response. Self-awareness and recognition of the psychological and physical responses getting out of control to decide to get help from professionals are crucial.

Hausdorff measure and extension results for subharmonic functions, for separately subharmonic functions, for harmonic functions and for separately harmonic functions

We give extension results for subharmonic, separately subharmonic, harmonic and separately harmonic functions. Our results improve previous results of Blanchet.

Targeting Inflammation: Window for Therapeutic Strategy in Head and Neck Malignancy

Inflammation is a hallmark of cancer. Inflammation is closely linked to head and neck malignancy and other solid tumors. Arrays of inflammation cascades and markers have been identified and proven to play significant roles in carcinogenesis. Many substances and molecules are secreted in response to the inflammation and its ecosystem and can be effectively measured and quantified at various stages of the carcinogenesis process. A spectrum of available inflammatory biomarkers can be a potentially effective therapeutic approach in the management armamentarium of head and neck malignancy. However, the cost, practicality, and availability are some of the major obstacles that need to be counteracted in order to progress in this challenging oncologic arena. Together with the continuous commitment from scientists, clinicians, laboratory personnel, and other related health staff, with the combination of technology updates, this new treatment approach and strategy are coming to reality. This chapter will discuss selected inflammatory biomarkers of significance critical for the armamentarium management of head and neck malignancy. Hopefully, this will escalate the treatment response of head and neck cancer patients. Hence, this ensures the patient’s survival with the best quality of life.

Behind the Screen: The Emergence of New Evidence

Head & Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous group of malignancies that collectively constitute a significant group of cancer worldwide. It affects not only the elderly patients but more so the middle age and the pediatric patient population. Around 90% of these tumors develop from the mucosal lining of the head and neck region i.e. Head & Neck Squamous Cell Carcinoma (HNSCC). These mainly include oral cavity carcinoma, oropharyngeal carcinoma, hypopharyngeal carcinoma, laryngeal carcinoma, sinonasal carcinoma, nasopharyngeal carcinoma, and salivary glands carcinomas. Different types of these carcinomas are prevalent at some geographic locations due to various environmental, dietary, social, and genetic factors. Head and neck cancers are critical as these affect many vital functions of the human being, such as breathing, eating, smell, hearing, and vision. Clinical and epidemiologic studies show aetio-pathological relation between chronic inflammation and cancer in several organs, including the Head and Neck region. A huge number of inflammatory mediators and markers have been identified and investigated in the current genomic era. Significant inflammatory biomarkers have a potential role not only in screening and prevention but also in treatment and assessing the prognosis of HNSCC. This chapter will highlight the recent facts, the discovery of evidence of the inflammation, and biomarkers for HNSCC.

Treatment of Head and Neck Cancer and Relation to Inflammation

Over the past decades, the survival rate of head and neck cancers has not significantly changed. Recently, the importance of the inflammatory responses in head and neck cancer has been a hot topic and of increasing interest. There has been suspicion about the relationship between inflammation and carcinogenesis, and thus, many works had proven these relations. Manipulation of the inflammatory mediators has been experimented with, to reduce the tumor burden, treat as well as prevent the cancer occurrence or second primary. This chapter summarizes the relationship between inflammation and cancer, emphasizing epidemiological and clinical evidence and proposing the current potential targets of anti-inflammatory agents for the therapeutic approach of head and neck cancer (HNC). We hope this knowledge will help us combat carcinogenesis and reduce the morbidity of the current conventional treatment for a better quality of life.

Inflammation and Current HPV Status in Head and Neck Malignancy

Head and neck malignancy is on the rise, where the majority of the tumors are squamous cell carcinoma (HNSCC). Previously, alcohol and tobacco are reported to be the well-established risk factors for HNSCC development. Currently, the HPV driven HNSCC has shown an increase in incidence globally, with oropharyngeal and oral cavity carcinoma predominating at certain geographic locations. HPV associated oropharyngeal squamous cell carcinoma commonly occurs in Europe and certain Western countries. They have different biological profiles compared to HPV-negative HNSCC. HPV-positive HNSCC patients have different characteristics and prognosis, which remarkably affect the management of this subset of patients. HPV is a significant inflammatory agent that can promote carcinogenesis via multiple critical mechanisms that are discussed in the chapters. Targeting HPV for future research is a great promising avenue for the discovery of novel screening, diagnostic, and therapeutic targets.

The Emergence of New Inflammatory Markers of Head and Neck Cancer and their Potentials

Inflammation plays a critical role in the process of carcinogenesis as well as in modulating treatment effects of many therapeutic agents for head and neck malignancy. Current research indicates that a myriad of new diagnostic tools and treatment modality works in harmony in producing a desired effective cancer treatment regime. Imperatively, multiple inflammatory markers have surged in the genomic and molecular ecospheres as highly potential agents that can be used in screening, diagnosis, treatment as well as follow up of head and neck cancer patients. These markers include arrays of cytokines, peptides, macrophages, acute phase proteins, growth factors, and many more. The tumor microenvironment is a complex ecosystem and has an intricate relationship with its surrounding biosphere. The multiple interactions within the molecules in the cancer microenvironment play significant roles in mediating and promoting carcinogenesis as well as mitigating the treatment response. These complex ecosystems are also responsible for the occurrence of metastatic diseases, recurrences, and residual diseases. This chapter highlights some of the critical inflammatory markers that can be potentially used as a potent theranostic approach for head and neck tumors in the near future.

The Diagnostic Tools for Head and Neck Cancer

Diagnosis plays a key role in overall patient assessment and accurate staging of the malignancy. Diagnosis is the starting point to choose treatment strategies for the disease, as well as the basis upon which therapy success, prognosis and the patient’s quality of life will vary. Considering a high level of clinical suspicion of any mucosal alteration or laterocervical swelling is important until medical examinations provide evidence of the contrary. Diagnosis investigation continues with the search, among data collected on the patient's history, of objective signs on which clinical suspicions will focus through further medical and instrumental examinations. Imaging techniques that can be used are ultrasound scan, computerised tomography, magnetic resonance and, in the most complex cases, positron emission computerised tomography. Ultrasonography is the most commonly used imaging technique for head and neck mass, especially for the assessment of lymph nodes, thyroid glands and salivary glands. Magnetic resonance is also considered an important examination in the diagnosis of head and neck tumours, especially for lesions involving the oral cavity, oropharynx, nasopharynx and larynx. Computerised tomography (CT) scan is especially useful when assessing the skull base involvement and the morphology of laryngeal malignancies, for example when the tumour extends over the perichondrium of cartilage structures, as well as when assessing function, i.e. evaluating the degree of chordal motility. In head and neck cancers (HNC), predictive factors namely biological characteristics that can be used to predict tumor response to a specific treatment, are currently remarkably lacking. Conversely, some bio-molecular parameters are recognized as prognostic factors of the disease, since they indicate tumor characteristics that inform about cancer outcome, independently of treatment the patients will undergo. The most prominent prognostic factor for head and neck cancers is viral etiology, specifically HPV-mediated disease for oropharyngeal carcinomas and EBV-mediated disease for nasopharyngeal carcinoma.

Inflammation, Risk Factors and Etiopathogenesis of Head and Neck Cancer

Head and neck malignancy is a critical disease across the globe as its incidence is on the rise. This malignancy comprises the oral cavity, oropharynx, larynx, nasal cavity, paranasal sinus, nasopharynx, salivary glands, and thyroid malignancies. Multiple known risk factors have been strongly associated with the majority of these malignancies. Importantly, the majority of these known risk factors are intricately involved in the inflammation and its ecosystem. Of note, inflammation cascades and inflammatory markers play a dominant role in the pathogenesis of head and neck malignancy. Thus, it is crucial to understand the true process of each identified risk factor and its related inflammation process in the etiopathogenesis of head and neck malignancy. This can serve as an effective platform for the future development of potential agents for screening, prevention, and treatment of head and neck malignancy. This chapter will discuss the significant risk factors of head and neck malignancy and highlight the spectrum of inflammation process that governs the basis of carcinogenesis and its etiopathogenesis.

Histological Classification of Head and Neck Tumors

Head and neck constituency tumor display many types of cell depending on the lineages, which can develop in a variety of tumor types. Nodaway, all these types and variants of tumor have been recognized based on histomorphological features and their molecular behavior. The most updated and receptive classification is provided by the World Health Organization (WHO) and the American Joint Committee on Cancer (AJCC). In the chapter, the discussion will include the common neoplasm, which can occur in oropharynx, nasopharynx, sinonasal region, salivary gland, thyroid gland and other adjacent structures. A brief overview, clinical presentation, histomorphology, genetic profile and outcome/prognosis will be highlighted.

Types of Head and Neck Malignancy

Head and neck cancer (HNC) is a heterogeneous group of malignant neoplasms, and its classification is a challenge. Based on the primary site, most literature comprehends five types of HNCs: laryngeal, pharyngeal, oral cavity, nasal cavity, and salivary gland cancer. More than 90% of HCNs are of epithelial origin, making squamous cell carcinoma the most common histological type. The prototypic HNC is a moderately differentiated squamous cell carcinoma associated with tobacco and alcohol consumption that affects older men more frequently. They are usually treated in a similar fashion. Currently, the human papillomavirus epidemic and a shift in tobacco consumption patterns are changing this trend. HNCs have a high rate of genetic heterogeneity, and molecular profiling has gained importance in the classification and future treatment of HNCs.

Introduction to Inflammation Ecosystem in Head and Neck Cancer

Head and neck cancer is on the rise around the globe. At present, the disease affects both the elderly and younger patient populations. This type of cancer is significant as it involves crucial anatomic regions of the head and neck, which are vital for breathing, mastication, swallowing, speech, and olfaction. The treatment options for head and neck malignancies are mainly surgery and chemoradiation, depending on the stage of the tumors. Inflammation plays an important role, and it has a strong relationship with the risk factors, assessment, and treatment of head and neck cancer. Multiple risk factors for head and neck squamous cell carcinoma like smoking, alcohol, viruses, chemicals, and foods have some elements of inflammation that play a dominant role in promoting and sustaining carcinogenesis. The inflammation cascades are complex, and multiple factors cohesively interact within the microenvironment that eventually leads to carcinogenesis, tumor recurrence, and metastasis. Recent evidence suggests that numerous anti-inflammatory biomarkers have effective therapeutic roles in the management of head and neck cancer. This chapter highlights the prominent relationship and interaction that exists between head and neck cancer and inflammation, not only in its etiopathogenesis but also in the assessment and overall management approaches. The significant focus is on the role of inflammatory agents that contribute to the process of carcinogenesis, as well as discussion on several significant inflammatory markers and molecules which may serve as a potential effective target for personalized treatment in head and neck cancer management armamentarium in the near future.

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Recent Patents on Exosome-Derived Therapeutic Agents

Exosomes are extracellular vesicles that are 30-150 nm in diameter. Exosomes have recently emerged as critical mediators of cell-cell communication by the transfer of DNA, RNA, and protein structured macromolecules between cells and tissues. With the advantage of the distant endocrine signalling, cancer cells use exosomes to suppress the immune system, next contribute to the formation of premetastatic niches and angiogenesis. On the other hand, researchers have been benefited from the immunosuppressive, natural carrier, and tissue regenerating roles of exosomes and disclosed patents that are claiming the utilities of exosomes for treating chronic inflammation, autoimmunity related diseases, targeted drug delivery vehicles, and tissue regenerating agents. Moreover, the use of exosomes as vaccine components to prevent cancer, therapeutic molecules for cancer treatment, and the host of biomarkers for the diagnosis and prognosis of cancer are among the issues that are protected by recent patents. The most inspiring one among them could be the incorporation of a therapeutic siRNA that is complementary to oncogenic KRASG12D into CD47+ exosomes for the treatment of pancreatic cancer. The other one could be the demonstration of the utility of exosomes secreted from dendritic as a cancer vaccine component in phase II clinical trial. It is clear that we have started to understand the fundamentals of exosomes. However, more studies are needed to develop exosomebased cancer vaccines, drug delivery vehicles, immune-stimulating agents that evoke immune cells to kill the cancer cells, and diagnostic and prognostic markers for monitoring cancer in the next years.

MHC and Cancer Immunotherapy

Major Histocompatibility Complex (MHC) is a gene region, which is named human leucocyte antigen (HLA) in humans. The human leukocyte antigen (HLA) system is a highly polymorphic family of genes involved in immunity and responsible for identifying self-cells versus no self-cells. Although HLA typing is essential for solid organ and bone marrow transplantation, at present, MHC is going to study on cancer immunotherapy increasingly. In order to introduce MHC related to cancer immunotherapy, the chapter aims at focusing on several MHC issues related to cancer immunotherapy. For example, MHC research and development (R&D) in MHC class I molecular loss related to cancer immunotherapy; tumor immune escape related to nonclassical MHC I; T-cell epitope vaccines; as well as MHC issues in adoptive immune cell therapy and personalized immunotherapy. In each part for MHC related to immune responses for tumor disease, we also introduce clinical uses in a study on MHC issues for T-cell immunotherapy, MHC for T-cell vaccines, and MHC TCR reconstructions for tumor shared/specific antigen related TCR T-cell personalized immunotherapy.

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Potential Natural Products For Prostate Cancer Management: Prospects For Castration-Resistant Patients

Prostate Cancer (PCa) is a major global health burden with alarming epidemiological indices. Research advances in this area have revealed complex molecular aspects associated with the disease, thus necessitating the novel development of diagnostic methods and therapeutic strategies. The main molecular target is the androgen receptor (AR), which is involved in both normal development and malignant transformation. However, many patients become resistant to conventional treatments, and the disease progresses to a castration-resistant stage (CRPC) in which tumor aggressiveness is driven by a constitutive activation of AR signaling. Tremendous effort has been made for elucidating CRPC and chemoresistance. In fact, multiple signaling pathways are related to the insurgence and maintenance of CRPC, highlighting the need for continuously updating such a complex scenario. Different drugs have been tested and used for CRPC treatment, facing unfavorable heterogeneity and leading to substantial morbidity and mortality. Thus, the clinical impact of advanced PCa with poorer outcomes still underscores the need for new compounds. The discovery and current use of natural products has given way to promising possibilities, offering alternative tools that aim to control the disease and to better manage patients. These natural products are versatile and effective molecules with different mechanisms of action and structures. In the present chapter, we explore the challenges of PCa and describe recent scientific contributions in this field, with special attention devoted to CRPC. We also discuss and suggest natural products as potential novel anti-tumor agents to overcome clinical limits and to treat and cure CRPC patients.

Drugs Affecting Adrenergic System

This chapter is a comprehensive account of medicinal chemistry of drugs affecting the adrenergic system. It provides the mechanisms of action of drugs and detail of structure-activity relationships of the adrenergic drugs to give the knowledge base for pharmacists. After the study of this chapter students will be able to:

• Comprehend the historical background of adrenergic neurochemistry and drugs acting on this system

• Explain adrenergic neurotransmitters and their functions

• Classify adrenergic receptors and their structures and binding

• Discuss direct and indirect acting sympathomimetic (adrenergic agonists) and sympatholytic (adrenergic antagonists) drugs

• Explain SAR for direct and indirect acting adrenergic receptor agonists and antagonists

• Delineate the clinical significance of these classes of drugs

• Identify the discovery process of these agents

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SGLT-2 Inhibitors: An Evidence-Based Perspective

Diabetes mellitus (DM) is one of the most prevalent diseases of modern society. There are several therapeutic options available, but they also have many shortcomings. With the limitations and pitfalls of the existing therapies of diabetes, there is always a need for better drugs. This review is an attempt to give comprehensive details about the merits and demerits of a class of drugs called SGLT-2 inhibitors. SGLT-2 inhibitors act by increasing glucose excretion through urine and do not have any effect on insulin secretion, therefore, the risk of hypoglycemia is less. SGLT-2 inhibitors that are in clinical use are: dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin. Considering the benefits offered by SGLT-2 inhibitors over existing antidiabetics, they deserve an important place in the therapy of T2DM and are found to be useful in T1DM, as studies have suggested previously. Beneficial effects of these drugs extend beyond controlling hyperglycemia, e.g., reduction in body weight, reduction in blood pressure and a proven and appreciable reduction in cardiovascular adverse events, maintenance of arterial elasticity and decrease in visceral adipose tissue deposition. The demonstration of such beneficial effects in various clinical studies has established them as one of the important components of antidiabetic therapy. However, in the light of recent safety concerns raised on such molecules would help prescribers to take an informed decision about risks versus benefits while prescribing these agents to their patients.

Perspectives of Deregulated Metabolism in Breast Cancer

Cancer cells devise different mechanisms to undergo aberrant cell division. Dysregulated signaling pathways and metabolic reprogramming are the two key mechanisms leading to cancer development. The role of metabolic dysregulation has been well known in cell proliferation, metastasis, and resistance to therapy, eventually leading to tumor progression. The dysregulation of enzyme activity and biochemical pathways have emerged as major factors in the metabolic reprogramming of breast cancer. The abnormal changes in the level of metabolites are mechanistically associated with the metabolism of cancer. Quantitative research studies have provided a list of metabolic biomarkers, which have a promising role in the early detection of breast cancer as well as in its therapy. Many of the current research studies are directed towards understanding the intricacies of metabolism in cancer cell proliferation. This chapter gives an overview of breast cancer metabolism with updated information and describes how deregulated metabolism plays a key role in the oncogenic cascade leading to the neoplastic transformation of cells.

Medical Management of the Obese Patient

Obesity is a common, chronic, complex, and multifactorial disorder and its management requires a multidisciplinary approach, including diet, exercise, behavior modifications, and drugs, all of which are key components of the treatment. Antiobesity drugs often have to be prescribed, despite adherence to appropriate lifestyle modifications. The goal of pharmacological management of obesity is not only to induce weight loss, but also to improve comorbidities associated with obesity, namely the components of metabolic syndrome, sleep apnoea, etc., and also to help patients maintain compliance, maintain body weight loss, prevent weight regain, as well as to improve their quality of life. The efficacy of the treatment should be evaluated after the first three months, and the drug should be withdrawal in nonresponders, or - if possible - an alternative therapy may be tried. There are marked differences regarding drug availability in the world, however the long-term use of approved antiobesity drugs is limited to five drugs (orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion, and liraglutide), all of which must be used in conjunction with lifestyle intervention. We will review currently approved antiobesity medications, focussing mainly on clinical aspects, and we will also discuss some of the new drugs that are in the pipeline.

Inscriptions: Introductions

This is the first of three chapters that address inscriptions found on the front panels of erect headstones. In this chapter, introductions are examined. These inscriptions appear towards the top of headstone front panels and often appear in large (ornate) letters. The trends evident for England and Scotland are noted here. Salvationinfluenced introductions, such as ‘Sacred’ and ‘In memory of’, were the most commonly used introductions in Britain, with the former (‘Sacred’) being more popular in England, while the latter (‘In memory of’) common in Scotland. These expressions displayed the changing views of death throughout the 17th and 19th centuries.

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Cytotoxicity Through Molecular Targets Involved in Apoptosis. Where Should We Further Search for Mushrooms Functionalities in Future Cancer Treatment?

Apoptosis is considered as a classical way of programmed cell death and important control mechanism of cell homeostasis. Cancer cells acquire different instruments to circumvent programmed cell death. This promotes uncontrolled growth and frequently confers chemoresistance to tumor cells. Activation of apoptotic signaling pathway has been a target of anti-cancer drugs in an induction of cytotoxicity. The mechanism of apoptosis is complex and includes many pathways. This chapter will focus on the current knowledge of apoptosis-triggering approaches in cancer therapy, as well as on mushroom extracts and isolated compounds acting as initiators of apoptosis through regulation of genes expression involved in cancer cell death. Furthermore, we pointed out directions for novel search for mushroom functionalities in this experimental field and discuss the possible further steps for exploration on the in vitro and in vivo levels.

Overview of Past and Present Developments Towards Biotechnological and Molecular Approaches to Improve Taxol Production

Taxol (paclitaxel) is one of the most used chemotherapeutic drugs, first isolated from Pacific yew tree T. brevifolia. It is used for several cancer treatments due to its unique mechanism of action. The demand for taxol supply was exceeded significantly due to its low accumulation in Taxus sp., slow growth of the tree and high cost of extraction. Due to these reasons, considerable efforts have been carried out to explore the alternative sources, including plants other than Taxus sp., total and semisynthesis of taxol, plant cell culture technology, and endophytic fungi. The biosynthesis of taxol is a complex pathway and several genes associated with taxol biosynthesis are identified and cloned. Transcriptomic studies of the critical genes involved in taxol biosynthesis pathway provided valuable insight in gene regulation patterns about metabolite synthesis. Also, recent advances in metabolic engineering have demonstrated the potential of genes regulation to increase taxol production. This chapter provides a more in-depth insight into basic and applied research to increase taxol production.

Plant Based Bioactive Compounds as an Alternative for Cancer Therapy

Medicinal Plants have been known to be one of the oldest and most consistent sources for the production of novel drugs. Utilization of plant extracts as drugs can be attributed to their chemical and structural diversity along with their ability to interact with different biological targets in the cell. Moreover, they act as huge reservoirs for the phytochemicals which provide defense against a number of diseases. Cost effectiveness along with lesser adverse effects, allowed natural plants to be used as an alternative to conventional strategies for cancer treatment. Extracts from different natural plants have also been explored in the treatment of infectious diseases. The present chapter emphasizes on the use of plant extracts and their purified compound as cancer therapeutics. Cancer is one of the major causes of mortality worldwide. Owing to several limitations of current treatment regimens of cancer, the attention of researchers has been drawn towards exploration of natural sources. Herein, we will focus majorly on bioactive compounds as therapeutic agents for cancer treatment with emphasis on their other possible beneficiary roles.

Natural Antimutagens. Chemopreventive Action of L-Ascorbic Acid and Green Tea Infusions on the Acute Toxicity and Mutagenicity of Reaction Mixtures Nitrite-Sulfonamide

An agent that causes irreversible and hereditary (mutation) changes in cellular genetic material, deoxyribonucleic acid (DNA) is defined as a mutagen. Changes in DNA caused by mutagens can damage the cells and cause certain diseases, such as cancer. Among the oldest and most recognized tests for the detection of mutagens we can mention those of Ames, which works with bacteria, and the test of the onion or Allium cepa test. One of the most effective ways to minimize the harmful effect of mutagenic substances is through the use of natural antimutagens. Natural antimutagenic substances, which may be present in plants, human diet and other sources have protective effects against mutagens. We showed that vitamin C and green tea infusions, in the Ames test, significantly mitigate the mutagenicity of sulfatiazole (a sulfa drug, an antibacterial commonly used) and nitrite (a food preservative and a normal body component) mixtures in acidic medium.

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Environmental Pollutants and Risk of Cancer

Cancer is characterized by cell proliferation, prevention or bypass of programmed cell death, genomic instability, angiogenesis, invasion and metastasis which are influenced by environmental pollutants. It is the major cause of death in world wide. Lifestyle factors such as diet, smoking and use of alcohol are responsible for the development of cancer in a large part of the population of developed countries. Existence of carcinogens or co-carcinogens in polluted air and drinking water, as well as in food, played a significant contribution in our country. Endocrine disrupters modify the risk of breast, endometrial and prostate cancer. Laryngeal, oropharyngeal, hypopharyngeal, sinonasal, nasopharyngeal, oral and lung cancer are positively associated with smoking and air pollutants. Tobacco smoking induces DNA adducts formation which is responsible for mutations at K-RAS and TP53 gene in the lung and pancreatic adenocarcinomas. Tobacco smoking induces promoter hypermethylation of p16 and DAPK genes in Non-Small Cell Lung Cancer (NSCLCs). Aflatoxin B1 (AFB1) causes promoter hypermethylation of tumour-suppressor genes RASSF1, MGMT, and p16 in human hepatocellular carcinoma (HCC) patients. Down-regulation of p15, p16, PRKG1, PARD3, and EPHA8 genes at mRNA level due to hypermethylation and increased expression of STAT3, IFNGR1 at mRNA level due to hypomethylation were reported in patients having benzene exposure. Methylationinduced transcriptional inactivation of tumor suppressor genes, including p53, CDKN2A (p16INK4A), Ras association domain family member 1 (RASSF1A), and death-associated protein kinase (DAPK) were reported in arsenic exposed individuals. The genetic and epigenetic alterations respond to environmental carcinogens have significant contribution for biomarker development in assessment of health risk.

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Polyphenols and Cancer

A solid and useful connection exists among eating regimen and malignancy. An inaccurate diet may increase the incidence of all types of cancer from 10% to 70%. Polyphenols are found in more than 700 foods, particularly foods grown on the ground (such as herbs), flavorings, and even nuts and cocoa items. Many food items considered superfoods; top superfoods include blueberries, apricots, grapes, olives and olive oil, artichoke, herbs (e.g., oregano, peppermint, and cloves), nuts and seeds (e.g., walnuts, almonds and flaxseeds), and green tea. Polyphenolic compounds can lead to epigenetic modification of chromatin and modulation of membrane organization; they can also interfere with interaction of the various macromolecules and regulation of the telomerase activity. They play crucial roles in modulating the multiple cellular pathways individually. Pure polyphenolic agents may be used as therapeutic agents, in combination with conventional therapy for improved cancer treatment. This chapter summarizes the anticancer efficacy of major polyphenolic compounds and discusses the potential mechanisms of action based on epidemiological studies.

In-vitro Anti-Proliferative Assays and Techniques Used in Pre-Clinical Anti-Cancer Drug Discovery

The hallmark features of cancer emphasize essential biological characteristics associated with malignant transformation. Anti-cancer drug discovery is a strenuous task, requiring a number of pre-clinical and clinical investigations. Preclinical investigations offer a foundation for anti-cancer drug discovery. A number of cell based in-vitro assays have been introduced to investigate each major hallmark feature of cancer. Selection of the most suitable in-vitro assay for pre-clinical investigations mainly depends on the researcher’s objective(s) to be investigated. A wide range of cell based in-vitro anti-proliferative assays/techniques have been developed based on different assay principles and chemistries to evaluate the effects of testing agent (s) on cancer cell proliferation. In this chapter, we have outlined commonly utilized cell based anti-proliferative assays in pre-clinical anti-cancer drug discovery approaches.

Pro-Apoptotic and Anti-Telomerase Activity of Naturally Occurring Compounds

A common hallmark of human cancers is the over expression of telomerase, a ribonucleoprotein complex that is responsible for maintaining the length and integrity of chromosome ends and often directly correlated with the uncontrolled growth of cancer cells. Telomerase activity is present in 85-90% of all cancers, but absent in normal cells, which makes telomerase a good marker for cancer diagnosis and prognosis. Also, telomerase inhibition can be used as a novel anticancer therapy with reduced probability of toxicity than present antimalignancy drugs. However, current treatments used for cancer such as radiation, anti-hormonal therapy, surgery and chemotherapy using synthetic drugs, have been reported to produce various side effects. Therefore, it is crucial to reveal the beneficial effects of natural compounds with lesser side effects on normal cells and potential anticancer activity. In recent years, several natural molecules have been discovered so far that arrest proliferation of cancer cells by inhibiting telomerase. In this book chapter, we highlighted the effect of natural compounds on cancer cell proliferation, telomerase activity and their mechanism of action.

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Combination Therapy of Hypothermia for Hypoxic Encephalopathy in Neonates

Perinatal brain injury remains a leading cause of mortality and morbidity in children. Neonatal encephalopathy (NE), which is primarily caused by hypoxicischemic (HI) events known as hypoxic-ischemic encephalopathy (HIE), is the predominant form of brain injury in term infants. NIE leads to high mortality and high incidence of sustained childhood disabilities among survivors. The past three decades witnessed significant progress towards a deep understanding of cellular and molecular mechanisms underlying HI-induced brain injury, yet basic research findings remain to be translated into clinical practice. Currently, the only available treatment option for HIE is therapeutic hypothermia, also known as targeted temperature management (TTM). Despite the successful translation from basic research into clinical use, TTM has several serious limitations including a narrow window of opportunity and a moderate efficacy leaving about 40-50% of treated infants still die or suffer from a significant neurologic disability. Hence, there is an urgent need to explore combined therapies which should broaden the therapeutic window and/or enhance therapeutic efficacy. In this chapter, we discussed several classes of neuroprotectants that showed promise in pre- and/or clinical settings. The first half of this chapter reviews advances in recent development of basic and clinical research in TTM, including major clinical trials. The second half focuses on potential candidate therapies to be combined with hypothermia.

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Alternative Models of Cancer Stem Cells: Implications for Translational Oncology

The classical cancer stem cell theory (CCSCT) proposes that tumors contain a subpopulation of rare cancer cells with stem-like properties (cancer stem cells, CSCs) that are organized hierarchically and are responsible for chemoresistance and tumor relapse. In this model, CSCs can generate non-CSCs, but this process is irreversible (unidirectional model). Experimental data provided evidence that cancer cells are extremely plastic in terms of stemness and that both CSCs and non-CSCs can interconvert into each other. As a result, alternative models of cancer stem cell biology such as the Stemness Phenotype Model, the Complex System Model, the Dynamic CSC Model and the Reprogramming Model have been proposed to reconcile experimental data with the working models of CSCs. These alternative models have profound implications for the development of new therapeutic strategies for cancer treatment. The aim of this chapter is to provide an overview of each of these alternative models of CSCs, their clinical implications and to discuss potential strategies to develop more effective therapeutic regimens for cancer treatment.

Sexually Transmitted Co-infections in Persons Living with HIV

Sexually transmitted co-infections increase HIV infectiousness through local inflammatory processes. The risk factors in acquiring genital co-infections associated with HIV infection still present many questions. There is some evidence that there is an association between certain sexually transmitted infections and HIV, but for others, there is only a marginal correlation, as will be discussed in this chapter. The most prevalent co-infections found in HIV carriers and their epidemiology, clinical features and evidence-based treatments will also be analyzed.

Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Systemic lupus erythematosus (SLE) is an inflammatory disease involving many systems, with different clinical features and laboratory findings. The etiology of SLE is unknown. The pathogenesis of SLE may derive from genetic as well as environmental factors. Overproduction of autoantibodies causes cytotoxic damage and takes part in immune complex formation causing inflammation. Clinical features may be general or result from inflammation in different organ systems including skin and mucous membranes, joints, kidneys, brain, serous membranes, lungs, heart and occasionally the gastrointestinal tract. The morbidity and mortality is associated with the involvement of vital organs, especially the kidneys and central nervous system, and is due to direct tissue damage or as a result of therapy. Lupus management is based on disease activity. Antimalarial drugs are effective for acute and chronic lupus rashes. Most clinical symptoms of SLE respond to GCS, however the adverse effects of GCS cause an increase in morbidity and must be tapered and withdrawn. Severe lupus (e.g. proliferative lupus nephritis, CNS involvement or severe thrombocytopenia) is treated by pulse IV methylprednisolone (MP) followed by oral GCS (0.5 mg/kg/day) and MMF or IV CYC, followed by less toxic AZA, MMF. To diagnose antiphospholipid syndrome (APS), a patient must have both a clinical event (thrombosis or pregnancy loss) and an antiphospholipid antibody (aPL), documented by a solid-phase serum assay (anticardiolipin – aCL), an inhibitor of phospholipid-dependent clotting (lupus anticoagulant – LA), or both. APS is treated by anticoagulation such as warfarin, heparin, and low-molecular-weight heparin and often in association with low-dose aspirin.

Bariatric and Metabolic Surgery

Obesity is a complex condition, one with serious social and psychological dimensions, that affects virtually all age and socioeconomic groups. It is a consequence of abundance, convenience and underlying biology. Preventing obesity requires changes in the environment and organisational behaviour, as well as changes in groups, family and individual behaviour. Treatment strategies vary in different centres and treatment sectors. Non-surgical management consists of diet, exercise, psychology and pharmacology. Non-surgical management can achieve weight loss. Anti-obesity drugs may be effective as adjunctive therapy to diet and physical activity in those subjects who struggle to lose weight despite following an appropriate weight loss programme. The problem with non-surgical treatment is of long-term sustainability. Bariatric surgery is the only management, which has long-term sustainability of weight loss and reversal of comorbidities. However, it is not applicable to all obese patients. Both restrictive and malabsorptive procedures have a relatively high success rate in weight loss and improvement of blood sugar control. However, these procedures have many pitfalls and complications. Experienced bariatric surgeons in high-volume centres have achieved minimal morbidity and mortality after weight loss surgery. Patient selection and preparation is key to success. Special anaesthetic considerations and modifications must be adhered to. The choice of procedure for any individual patient is a complex process and depends on many factors. Follow-up after bariatric surgery must be rigorous to monitor and correct micronutrient deficiency and provide psychological support to patients who have had to change their life style albeit to a healthier existence.

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Pediatric Hematological Malignancies – Clinical Manifestation, Treatment and Follow-Up

Hematological malignancies are the forms of cancer that begin in the cells of the blood- forming tissue, such as the bone marrow. Childhood blood cancers are relatively rare but are still found to be the major cause of death in children aged 1-14. Early detection increases the chances of successful treatment which paves the way to reduce the rate of mortality. Leukemias and lymphomas account for more than one half of new cancer cases in children. Despite major advances – from an overall survival rate of 10 percent to nearly 90 percent today, for many rare cancers, the survival rate is much lower. Enhancement of anti-leukemic efficacy and reduction of treatment related morbidity or mortality can be achieved by targeted therapy, but requires detailed understanding of pathways and genetic defects involved in leukemogenesis.

Types of Benign or Malignant Diseases Associated with HPV Infections

During the last years, several researchers have properly focused on classifying variants of human papillomaviruses (HPVs). HPV variants are different in their biological, molecular and chemical properties. Thus, this genomic diversity can represent differences in the natural history and pathogenicity of HPVs. For instance, high-risk HPV variants such as HPVs 16 and 18 can confer various risks of viral persistence in the human cervix and cause cervical cancer. Moreover, low-risk HPV variants including HPVs 6 and 11 can play an important role in the development of anogenital and cutaneous warts, and recurrent respiratory papillomatosis (RRP). Herein, we will discuss main and novel types of HPVs and their correlation with intensity of diseases.

Cancer Chemo-Immunotherapeutics

Cancer chemo-immunotherapeutics has evolved with a strategic slogan - ‘marrying chemotherapy with immunotherapy’ - in order to optimize the chance for cure. The ultimate goal is to execute a ‘two hit’ impact, able on the one hand to mount a robust anti-tumour immune response, and on the other hand, selectively eradicate tumour growth and progression. Tremendous progress has been, and being, made in this regard by testing various ‘chemotherapy-immunotherapy’ drug combinations in the clinic, and also implementing multiple pharmacological and biological interventions against fundamental regulatory pathways involved in tumour development, progression, and tumour immune escape mechanisms. This chapter discusses the current ‘chemotherapy-immunotherapy’ combinations in clinical studies/trials, as well as the pharmacological manipulation of host-tumour cell interactions mapping the road ahead to a novel trend/concept of ‘two hit’ chemo-immunotherapeutics. At the end, we also discuss the patents issued and recent patent applications stating the novel chemoimmunotherapy methods with diverse interventional combinations, some of which produce synergistic anti-tumour effects, to treat multiple advanced cancers.

Foods and Nutrients as Adjuvants in Cancer Chemo-prevention and Treatment

Foods and nutrients may be useful sources in preventing and treating cancer. Substances like resveratrol, curcumin, pomegranate and honey have turned out to be much promising agents for combating tumor cells, especially for overcoming chemoresistance. Compounds like resveratrol, which is abundant in red wine, red grapes, blueberries, peanuts and pistachios seem to induce p53-dependent apoptosis. Identification of a receptor of resveratrol in tumor cells, supports the potential of this substance as an anti-cancer agent. This receptor could serve in studies of future resveratrol analogues. Resveratrol is documented to surpass chemo-resistance through inhibition of NF- κB as well as the STAT3 pathway. Resveratrol has shown much promise in preclinical trials and because of its good safety profile it may be an ideal chemo-preventive and chemotherapeutic agent. Curcumin, a yellow component which belongs to the superfamily of polyphenols, is the most potent substance of turmeric, an Indian spice derived from the Curcuma longa plant. Curcumin and its analogues deploy their anti-tumor effects by inhibiting the STAT3 and the NF-κB, which play pivotalroles in the evolution of tumor cells. Furthermore, it has been demonstrated to inhibit focal adhesion kinase (FAK) phosphorylation and enhance the expressions of several extracellular matrix components, which play a pivotal role in invasion and metastasis. Curcumin has been shown to enhance cell adhesion ability, through induction of extracellular matrix substance collagen, fibronectin, and laminin. Taken together, it is suggested that curcumin suppresses FAK activity by means of inhibition of its phosphorylation sites and also induces extra-cellular matrix components to enhance cell adhesion ability, thus, preventing detachment of cancer cells and cell migration. Honey comprises of vitamins, including ascorbic acid, pantothenic acid, niacin and riboflavin and minerals like calcium, copper, iron, magnesium, manganese, and phosphorus. Also, honey is suggested to exhibit anti-cancerous features, while its antiproliferative and apoptotic effects vary according to the “floral origin and the phenolic content”. Finally, the role of pomegranate juice and/or pomegranate extracts in preventing and treating various tumors, especially prostate cancer will be discussed in this review. The pomegranate fruit is derived from the tree Punica granatum and is cultivated in Mediterranean countries, Russia, India, China, Japan, and the United States. The anti-oxidant properties of pomegranates have been demonstrated to be better compared to red wine or green tea, two dietary compounds which have been promising in preclinical prostate cancer cell lines for reducing metastasis, mainly through inhibiting matrix substances. The roles of resveratrol, pomegranate, honey as well as curcumin as weapons in our battle against cancer will be further elucidated in this review. Many more studies are needed in order to determine the exact dosage of each of the above-mentioned compounds for the prevention and treatment of various types of cancers, respectively. In this view, bioavailability of those substances has to be improved, whilst the maximum dosage that does not cause any serious adverse effects in humans has to be established. In particular, future studies should focus on ameliorating formulas of the above-mentioned compounds, by improving their absorption and kinetics as well as by minimizing adverse side effects, which are estimated to be often in doses that are really helpful for humans in the clinical setting.