Heart Valve Diseases

Cyber-Physical Systems in HealthCare

Cyber-Physical Systems (CPS) are being developed with the integration of computational capabilities and communication with physical systems. Recent technologies like WSN (Wireless Sensor Networks), Communication Networks, Cloud Computing, Big Data, and many more use CPS. Applications include Smart Grid, Healthcare, Transportation, and Smart Buildings. CPS has made a huge impact on increasing the efficiency of medicines and life span in many developed countries. This has drawn researchers and the government's interest in Medical Cyber-Physical Systems (MCPS), especially during Covid times. Many models were developed during the pandemic. One of them is a Machine Learning (ML) integrated X-ray device called Covilearn. In this chapter, an introduction to CPS in health care, its current trends, and a device called e-stocking has been discussed. It is being used to treat leg venous insufficiency. The motive of the application of CPS is to reduce power consumption for long-term usage. This system is based on a model-driven energy-aware approach. There are three approaches - Mechanical, Software, and Communication. False alarm is one of the major issues as it is a pressure on both patients and caretakers. A model aimed at resolving this problem is proposed and discussed here. Also, the existing challenges and prospective opportunities in the domain of CPS have been explored.

Common Surgical Procedures in Geriatric Patients

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

Anesthetic Considerations in Patients After Valve Replacements and Cardiac Stents, with Associated Anticoagulation Concerns

Geriatric patients are a significant proportion of the patients seen in the perioperative setting. Oftentimes, these patients are presenting for non-cardiac surgery after undergoing a cardiac procedure previously. Management of these patients starts with understanding the pathophysiology, surgical intervention, and anesthetic considerations. This management starts from risk assessment and perioperative management. In this chapter, risk assessment stemming from a patient’s co-morbid conditions is taken into account to form an overall risk profile. These conditions help the anesthesiologist establish a framework to model an anesthetic plan. Notably, a prior cardiac history, including a history of coronary artery disease (CAD), hypertension (HTN), and a history of valve disease and possible repair, is prudent. Also discussed is the need for appropriate intra-operative monitoring in specific situations as well as anticoagulation guidelines in the pre and post-operative settings.

Postoperative Cognitive Dysfunction (POCD) in Geriatric Patients

As the world population ages, the number of older patients undergoing surgery will increase significantly. Postoperative cognitive dysfunction (POCD) and other perioperative neurocognitive disorders (PND) affecting patients after surgery have long been recognized in older patients and are considered some of the most common postoperative complications. POCD has been correlated with significant morbidity and mortality, and greater healthcare costs. Historically, the lack of standardized nomenclature used to describe cognitive change after surgery and anesthesia has made it challenging to conduct systematic reviews or analyze the results of similar studies to further understand the clinical implications of this disorder. This has led to minimal recognition of this disorder outside of the specialty of anesthesiology. Patient and surgery-related risk factors include old age, preexisting cognitive changes, and emergency surgery amongst others. Proposed etiologies include postsurgical neuroinflammation, impairment of neurotransmitter systems, and cerebral vascular events in the perioperative period. The medical literature offers little guidance to recommend a particular anesthetic to decrease the risk of POCD in the postoperative patient. Most studies found similar risks of POCD after general and regional anesthesia techniques. While there is no standardized test for diagnosing preoperative cognitive impairment, it is critical to identify high-risk patients so that timely interventions can be made to minimize POCD.

Modulatory Mechanism of NLRP3 Inflammasome in Heart Diseases: “An Enigma Wrapped in a Riddle”

Despite breakthroughs in therapy over the prior two decades, heart failure is considered the foremost cause of mortality globally. The inflammasome plays a pivotal role in the advancement of heart failure, abdominal aortic aneurysm, atherosclerosis, diabetic cardiomyopathy, hypertension, dilated cardiomyopathy, cardiac remodeling and calcific aortic valve disease. The NLRP3 inflammasome is a crucial multi-protein signaling platform that tightly regulates inflammatory responses. It regulates antimicrobial host defense, which causes pyroptosis through caspase-1 activation by the eventual production of pro-inflammatory cytokines. The investigation of the NLRP3 inflammasome in various cardiovascular diseases may reveal critical disease triggers and endogenous modulators, leading to the development of new therapeutic interventions in the future. The target of this chapter is to summarise the recent literature describing the activation mechanism of the NLRP3 inflammasome by implicating different inflammatory pathways in the pathophysiology of heart failure.

Preface

Cardiovascular Examination

The Cardiovascular examination is typically focused in cardiac and blood vessels. Cardiovascular disease may present with a number of diverse symptoms; non-cardiac causes must also be considered. It allows for an initial assessment of symptoms and is crucial for determining the differential diagnoses and further steps in cardiac diseases. The present chapter gives students details in manual cardiac examination and makes it easy for medical students and junior doctors.

General Physical Examination

Physical examination is a fundamental aspect of medical practice that involves a systematic evaluation of a patient's body to assess their overall health status and identify any signs of illness or abnormalities. It is typically performed by healthcare professionals, such as physicians, nurses, or other trained medical personnel. The physical examination can provide valuable information that aids in the diagnosis, treatment, and monitoring of various medical conditions. The physical examination, thoughtfully performed, should yield 20% of the data necessary for patient diagnosis and management. The present chapter is mainly focused on how to apply physical general examination

Application of Nanomaterials in the Medical Field: A Review

Nanomaterials are particles in sizes from 1-100 nm. Nanomaterials have a wide field of applications in aviation and aerospace, chemical industries, optics, solar hydrogen, fuel cell, batteries, sensors, power generation, aeronautic industry, buildingconstruction industry, automotive engineering, consumer electronics, thermoelectric devices, pharmaceuticals, paints, and cosmetics. Also, efforts are being made to develop friendly alternate energy sources using nanomaterials. In this chapter, the main focus will be on the application of nanomaterials in various aspects of the medical field. Nanomaterials are used in various medical devices. Some of the nanomaterials used in the area of optical imaging are quantum dots, and in MRI are superparamagnetic iron oxide nanoparticles. Also, nanomaterials are applied in ultrasound imaging and radionuclide imaging. Due to the small size of batteries (e.g., for pacemakers) or electronic circuits and sensors utilized in medical devices presently made using nanomaterials. New ceramics consisting of materials derived from sintered nanopowders (comparable to 3D-printing) or having a specially designed surface are made from so-called nanostructures for teeth filling or screws for dental implants. For bio-detection of pathogens, detection of proteins, and phagokinetic studies, nanomaterials are also used. For fluorescent biological labels, drug and gene delivery, probing of DNA structure, tissue engineering, tumour destruction via heating (hyperthermia), separation and purification of biological molecules and cells, MRI contrast enhancement, osteoporosis treatment, infection prevention, bone regeneration are some of the applications of nanomaterials used in medicines. Cancer therapy, neurodegenerative disease therapy, HIV/AIDS therapy, ocular disease therapy, respiratory disease therapy, sight-restoring therapy, and gene therapy are various therapies nanomaterials are used Nanomaterials used in various surgeries are surgical oncology, thoracic surgery, replacement of heart with an artificial heart, vascular surgery, neurosurgery, radiosurgery, ophthalmic surgery, plastic and reconstructive surgery, maxillofacial surgery, orthopedic surgery, intracellular surgery by nanorobots. Although all applications of nanomaterials have pros and cons, care should be taken so that the cons can be minimized.

Drug Therapies against Acute Respiratory Distress: A Critical Endpoint of COVID-19

Pulmonary diseases have been increasing for decades, which are responsible for the high incidence of morbidity and mortality all over the world. Since the year 2019, the world suffers from coronavirus disease 2019 (COVID-19) which is caused by SARS-CoV-2 and it was classified as a pandemic respiratory disease by the World Health Organization (WHO). The problem of this virus is the lack of a medicine or a specific antivirus drug to combat it, so many approaches have been designed to protect the patients from its symptoms and side effect and also to raise the human innate immunity. Consequently, this chapter will provide an overview of herbs and their derived natural products which have anti-inflammatory, immunomodulatory, and anti-microbial activities which might be beneficial for the discovery of structurally-related compounds that can be candidate therapeutics alleviating the symptoms associated with acute respiratory diseases.

Meconium Stained Newborn

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

Management of Children with Systemic Diseases

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

Hepatoprotective Phytochemicals: Isolation and Characterization from Plant Extracts

The liver is the body's primary organ responsible for metabolism and excretion. Oxidation, reduction, hydration, condensation, hydrolysis, conjugation, and isomerization are some of the metabolic routes used by the human liver to metabolise chemicals. Any of the aforementioned processes can be disrupted, resulting in liver cell damage or hepatotoxicity, which can lead to a variety of disorders. These disorders are linked to increased death rates over the world. Medicines, chemicals, dietary changes, and herb-induced liver injury via hepatotoxins can all cause hepatotoxicity. A number of herbal and herbomineral preparations are available in Ayurveda, the traditional Indian Medicine, which has been investigated for their hepatoprotective potential to treat different types of liver disorders. The present review is focused on different herbal plants that have the potential to cure hepatotoxicity.

Likes and Dislikes: Cell Preference in the Context of Biomaterials

Cell adhesion is a complex mechanism that involves a dynamic interaction between the cell surface protein and specific ligands. It has become a crucial part to be understood when it comes to cell adhesion to biomaterial, especially in the tissue engineering field. In this chapter, we narratively discussed the basic principle of cell adhesion and the factors that affect this process. The characterisation of cells on biomaterials has also been discussed, as well as their application in the tissue engineering context.

Oxidative Stress and Leukocytes Activation - The Two Keystones of Ischemia/Reperfusion Injury during Myocardial Infarction, Valve Disease, and Atrial Fibrillation

Oxidative stress is a major contributor to ischaemia reperfusion injurymediated myocardial infarction. Coronary ischemia deprives the heart muscles of nutrients and oxygen in the areas away from the site of arterial blockage, rendering cardiomyocytes unable to utilise aerobic metabolism to support their energy requirements. Homeostatic intracellular signalling systems, such as the hypoxiainducible factor (HIF) transcription factor cascade, sense the low oxygen environment. This in turn stimulates the upregulation of numerous compensatory mechanisms which are ultimately involved in elevating anaerobic glycolysis and promoting angiogenesis and vascularization. The increased anaerobic metabolism increases the production of lactic acid hence metabolic acidosis. This leads to myocyte death and the expansion of the size of the original area of the infarct. Under normal aerobic conditions, the myocardium generally metabolises relatively high levels of adenosine triphosphates (ATP). In contrast, during ischemia, the shift in energy production to glycolysis results in the inefficient production of ATP and constitutes a pathological feature, and if not reversed early, it may lead to complications such as heart failure and ischemia-induced atrial or ventricular fibrillation. Despite the widespread use of fibrinolytic agents and new types of angioplasty procedures for the treatment of myocardial infarction, often new sets of complications persist. These include the occurrence of extensive tissue injury caused by myocardial reperfusion through the reintroduction of oxygen to the previous ischemic tissues because of the excessive generation of reactive oxygen species (ROSs) and depletion of antioxidants. Widespread production of ROS damages the plasma membrane and stimulates the release of various proinflammatory agents. Several proteins become denatured for example receptors, ionic channels, transporters, or components of transduction pathways through oxidation by ROS. Altered protein structure inhibits their functions leading to the disruption of vital cellular processes. The onset of reperfusion injury is further exacerbated by the activation and infiltration of the infarcted area by polymorphonuclear leukocytes (PMNs). Several studies have identified the release of different leukocyte intracellular factors during PMN activation such as selectins and b2-integrins to be related to the magnitude of tissue damage. Some studies have shown that antagonists for leukocytes intracellular factors such as selectins abrogate PMN activation and reduce the infarct size.

More recent publications have shown that PMN activation is closely linked to the activation of other cells involved in the inflammatory response. For example, during myocardial ischemia–reperfusion injury, it has been shown that the activity of neutrophils is also modulated by lymphocytes and macrophages. This chapter summarises the interaction between oxidative stress, activation of different leukocytes and the release of factors involved in the generation of reperfusion injury.

Chromosome 5

Chromosome 5 presents an extensive collection of genes, and includes several cancer-associated ones. The contribution of chromosome 5 in abnormalities is evident through somatic translocations, germline, somatic, and, in some instances, expression of genes. Various syndromes are associated with chromosome 5, such as 5q minus syndrome, leading to the development of acute myeloid leukemia, PDGFRBassociated chronic eosinophilic leukemia contributing to acute myeloid leukemia, and myelodysplastic syndromes. Studies propose that a few genes on chromosome 5 play important roles withinside the increase and department of cells. When chromosome segments are deleted, as in a few instances of AML and MDS, those crucial genes are missing. Without those genes, cells can develop and divide too speedy and in an out-o- -control way. Researchers are trying to perceive the genes on chromosome five that might be associated with AML and MDS.

Activity Methods for Cardiovascular System Diseases

This chapter provides a collection of methods generally used in experimental pharmacology to test compounds with different activities in the cardiovascular system. There are many models in vitro and in vivo and we have highlighted those used in the field of natural compounds research. For the in vitro procedures, the focus was on the inhibition of enzymes, such as an angiotensin-converting enzyme or nitric oxide synthase, which plays a pivotal role in maintaining vascular control and overall blood pressure. Moreover, test procedures on isolated vessels were also considered for compounds whose activity is exerted on specific targets expressed in the vasculature. Regarding the in vivo methods, heart failure and hypertension models were highlighted for their high incidence of overall deaths cause. In particular, we have analyzed models of heart failure in rats and mice, animals generally used in preclinical studies. In addition, it also evaluated useful models of hypertension involving mainly rats; however, in many cases, the procedure could be translated to different animal species.

Hydrops Fetalis and Fetal Alloimmune Thrombocytopenia

Urogenital Abnormalities

Congenital Heart Disease

Material Synthesis, Structures and Characterization

Polymers have been employed for the development of medical devices and implants as some of them are biocompatible. Synthetic procedures and extraction techniques have allowed the obtention of different polymers, classified in this chapter as synthetic and natural polymers. In the process of synthesis of the polymer, its properties can be modulated to obtain more flexible or thermostable materials, nontoxic or transparent, depending on the desired properties of the final product. A wide range of polymers have been used for the manufacturing of catheters, valves, tubes, and other medical devices; therefore, in this chapter, there is a brief description of some of them, their chemical structure and properties, and finally, their application in medicine is shown.

Repurposed Drugs/Potential Pharmacological Agents Targeting Cytokine Release and Induction of Coagulation in COVID-19

Global public health has been challenged by the coronavirus 2019 (COVID- 19) and has been a threat to clinical management to fight this viral infection. Due to the lack of specific therapies, there is a race among the scientific fraternity to find its specific cure to date. COVID-19 symptoms range from mild fatigue to potentially fatal pneumonia, cytokine storm (CS), and multi-organ failure. Hence, investigating the repurposing of current medications for use in the management of COVID-19 patients is a realistic approach. It is prudent to investigate using repurposed medications in the management of COVID-19 patients. In the meantime, researchers are testing a number of antiviral and immunomodulatory medicines to combat the infection. Although antiviral as well as supportive medications are undoubtedly vital in the treatment of COVID-19 patients, anti-inflammatory agents play an essential part in COVID-19 patient care due to their potential to prevent additional injury and organ damage and/or failure. Moreover, COVID-19-mediated infection can be linked with coagulopathy. The most common thrombotic events in COVID-19 are venous thromboembolic (VTE), which are linked with increased severity of disease and poor clinical outcomes. Here, we evaluated medicines that potentially modulate pro-inflammatory cytokines and assist in COVID-19 management. We emphasized various pro-inflammatory cytokines as targets of repurposed drugs and targeted induction coagulation in COVID- 19 patients using the available literature and studies.

Taurine and the Mitochondrion

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

Nanocarriers For Drug Targeting

Drug targeting specific cells/tissues of the body without their becoming a part of the systemic circulation is a prominent area of research in drug delivery, with the main emphasis on improvement in formulation and development. Drug-targeting can improve the viability, lower/minimize the adverse/side effects, and can become cost-effective. Certain limitations like short circulating half-life, bioavailability issues, rapid metabolism and degradation, poor tissue distribution and penetration in the blood-brain barrier, intestinal absorption barriers, etc., are associated with the delivery of various therapeutic agents. Nanocarriers have arisen in the field of drug targeting with valuable delivery of drugs to site-specific/desired areas which is a significant therapeutic advantage since it keeps drugs from being conveyed to some unacceptable spots. Nanocarriers prevent the obstacles in clinical utilization of the therapeutic agents as they decrease the serious and critical side/adverse effects by targeted drug delivery and provide slow and sustained drug release. Nanocarriers bring new trust to drug targeting by upgrading the efficacy, defeating resistance, and minimizing toxicity. This chapter mainly focuses on the role and benefits of nanocarriers in drug-targeting and nanocarriers as prominent systems for targeting and delivering drugs to achieve maximum effects with improved therapeutic response.

An Overview on Nanoparticulate Drug Delivery System for its Specific and Targeted Effects in Various Diseases

In modern-day medicine, nanoparticles and nanocarriers are rapidly evolving fields in therapeutics and are the building blocks of nanomedicine, which emphasize the use of nanoscale particles that have a wide array of functions from working as a diagnostic tool to the screening, monitoring, and controlling of various diseases to the delivery of drugs at specific targets in a controlled manner. With the advancement in technologies, it is proven that nanoparticles have a greater potential in wide biomedical applications. Due to their ability to bind with both hydrophobic and lyophilic substances, lower particle size, higher carrier capacity, nanoparticles serve as a favorable platform for specific and targeted drug delivery in disease treatment. Nanoformulations can improve the safety, pharmacokinetic characteristics, and bioavailability of administered drugs, and can improve the therapeutic effect when compared with conventional therapies. Besides, nanoparticles may also be effective in delivering nucleotides, vaccines, and recombinant proteins. Several varieties of nanoparticles are available: different metal and polymeric nanoparticles like gold/silver nanoparticles and micelles, dendrimers. Carbon-derived nanoparticles like quantum dots, carbon tubes, and many other nano assemblies. Numerous nanocarriers, nanoparticle-based drug delivery systems, and drug targeting systems are either developed or under development. In this chapter, we will emphasize mainly the specific and targeted nanoparticles and the use of various nanocarriers for the targeted delivery of drugs in various diseases. The opportunities and challenges of using nanoparticles/nanocarriers in targeted delivery along with its clinical applications are also discussed here.

Air and Amniotic Fluid Embolism

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

Hypertensive Disorders in Pregnancy

Due to the high risk of morbidity and mortality in pregnant women with unrecognised and untreated preeclampsia, a high index of suspicion for signs of preeclampsia should be used to evaluate, treat and monitor patients. Early blood pressure control and seizure prophylaxis during labour are essential to ensure maternal safety. However, a limited proportion of pregnancies and deliveries may present a wide range of complications that may require admission to a critical care unit (CCU). Hypertensive disorders of pregnancy and massive hemorrhage are among the most common causes of admission to the CCU in pregnant and post-partum women.

Anesthesia for Fetal Surgery

Fetal surgery has evolved in the last decades, mostly because of the technical advances in therapeutic and monitoring devices. The timing and mode of surgery depend on the disease to be treated. Local, neuraxial or general anesthesia can be used on the mother. In some cases, fetal analgesia and paralysis are needed. The idea of treating the fetus as a patient has evolved in recent years, as a consequence of improvements in diagnostic imaging and surgical devices. In fetuses with congenital airway obstruction, intrapartum surgical correction or airway management can be performed while maintaining perfusion via the umbilical cord. In 1980, maternal laparotomy and hysterotomy were proposed to treat fetuses with congenital and developmental abnormalities, and the prerequisites for maternal-fetal surgery were first formulated in 1982. They are still in use with some minor modifications. A multidisciplinary approach to fetal intervention is essential. Both obstetric and pediatric anesthesia is involved and it a close collaboration with surgical teams is necessary.

Subject Index

Medicine and Engineering “Engineering is Supportive to Medical Instruments and Software”

The main theme of this chapter is to supplement medical examinations with biomedical means, which is only possible with mutual collaboration between doctors and engineers. The principles of science and technology-based tools are explained by engineering design concepts and software possibilities, which are supportive aids for medical diagnosis. Various sections of this chapter provide a linguistic explanation of the engineering related medical issues followed by a logical explanation of mathematical expression derivations through various models based on a set of assumptions. In the explanations, bivalent and fuzzy logic principles are used according to the problem at hand. Population growth, food sharing, injection, diabetics, dialysis, epidemics, sensitive hearing intake, blood circulation, etc. problems are modeled using a set of convenient mathematical methodologies. Human engineering concepts are discussed from the medical point of view. Finally, a set of recommendations are given for possible future directions to arrive at better innovation.

Applications of Internet of Things in Telemedicine

The term ‘telemedicine’ is referred to as healing remotely with the help of digital technologies by healthcare providers to detect and treat sufferers. Due to necessary physical distancing and lack of appropriate treatments during the Covid-19 pandemic times, telemedicine has proven to be a secure interactive mechanism between patients and medical professionals. The telemedicine framework is part of the Internet of Medical Things (IoMT) since it allows many medical devices to connect and share data. IoT has a lot of benefits in Telemedicine. It aids doctors in gaining access to vital data from medical devices, real-time monitoring of patients, assisting sick and elderly people, and distant medical support. Apart from benefits for patients, it also benefits hospitals and insurance companies. Moreover, distant monitoring of a patient's condition tends to shorten hospital stays. It has a huge effect on lowering healthcare costs and enhancing treatment methods. Many wearable devices, like heart rate monitoring devices, blood pressure monitoring devices, glucometers, etc., provide a way to access the patient’s health information. The proposed study revealed different applications of IoT in healthcare for various diseases and disorders, various medical sensors, and notable wearable devices in healthcare.

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

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

Rodent and Non-Rodent Animal Models for CardioVascular Diseases

Cardiovascular diseases (CVD) come under non-communicable disease (NCD) that are responsible for the leading cause of death, globally. They involve a range of pathologies viz. coronary artery disease, cerebro-vascular disease, venous thrombo-embolism, peripheral vascular disease, myocardial infarction, cardiac arrhythmias and stroke. Each pathology is the result of the complex interplay of many factors which determine the prognosis of the condition. Animal experimentation has played an important role in the fundamental understanding of pathologies of cardiac diseases and discovered improved methods of diagnosis and treatment. Researchers have used a number of lab animals that involve rodents (mice, rats, hamsters, and rabbits) and non-rodent animal models (dogs, pigs, sheep, primates) as a biological system to mimic cardiovascular diseases for translational research. An ideal animalmodel system should be cheap, readily manipulable, reproducible, ethically sound and reflect the complexity of cardiovascular diseases. Rodent animal models are considered the prime model for human research. Common rodent models include mice, rats and hamsters; rabbits are used for studies on cardiac hypertrophy, heart failure, aortic constriction, pulmonary vein constriction, atherosclerosis and cholesterol regulation studies. With the advancement in genetic engineering, several transgenic/humanized rodent models are available which can mimic better human systems for translational application. Among non-rodent animal models, pigs, dogs, sheep, and non-human primates serve as an excellent model in cardiovascular research; owing to the similarity in heart structure, atrio-ventricular valves, lipid metabolism and vasculature with humans. In the current chapter, we will deal with the importance of the models and their characteristic features, advantages and limitations.

Congestive Heart Failure: Insight on Pharmacotherapy

Congestive Heart Failure (CHF) is the inability of the heart to supply blood to other organs and tissues to meet its need for metabolism. Over 64.3 million people around the world live with heart failure. Some of the common causes of CHF include myocardial infarction, increase in blood pressure, atrial fibrillation and cardiomyopathy. The complete etiology of CHF is complex. Patients with HF often experience fatigue, dyspnea, and pain, lack of energy, cognitive impairment and depression. Left ventricular ejection fraction (LVEF) is a measure of the amount of blood pumped from the heart's left ventricle during each contraction. It is used as a phenotypic marker in the indication of the pathophysiological mechanism and sensitivity to therapy. The pathogenesis of HF with low ejection fraction is that of a progressive state. The various classes of drugs used clinically for the treatment of congestive heart failure are diuretics, beta blockers, ACE inhibitors and vasopressin receptor antagonists. The management of Heart failure includes acute decompensation, chronic management and palliative care. Cardiac glycosides are a varied group of naturally obtained compounds used in the treatment of CHF. They exhibit their action by binding to and inhibiting Na+/K+-ATPase. Then, they consequently increase the force of myocardial contraction. The primary structure of these drugs is a steroidal framework, which is the pharmacophoric component that is responsible for their activity. The most familiar cardiac glycosides are digitoxin, digoxin, oleandrin, bufalin, ouabain, marinobufagenin, telocinobufagin and aerobufagenin. Among other cardiac glycosides, digoxin has been proven to improve symptom alleviation, functional capacity, quality of life and exercise tolerance in patients with mild to moderate HF in clinical trials. Early detection and prevention interventions, as well as lifestyle changes, are essential.

Polymers in Localized Controlled Drug Delivery Systems (LCDDSs)

Polymeric and biopolymeric materials and nanostructures have been extensively used in drug delivery, and especially in the development of localized controlled drug delivery systems (LCDDS). Stimuli-sensitive biopolymeric materials are achieving remarkable consideration as smart multipurpose systems that exhibit superb potential in several applications. LCDDS allow high delivery levels at the target area, low cytotoxicity, excellent biocompatibility and prolonged drug exposure that can be helpful for targeted cellular therapeutic molecules. This chapter focuses on synthetic and natural degradable biopolymeric materials for LCDDS, focusing on their advantages, challenges, and clinical applicability. Recent progress in typical and stimuli-sensitive biopolymeric materials has also been reviewed. The features of biodegradable polymers and biopolymers for various purposes are discussed, and the advantages of these materials and biomaterials are highlighted. Moreover, different emerging functions of these polymers in a drug delivery system are discussed.

Subject Index

Nanotechnology and Health

Nanomedicine is a reality nowadays. The first generation nanomedical capabilities, in the form of functionalized nanoparticles, comprising a wide range of organic and inorganic materials at various nanoscale dimensions, initially emerged in the early 1990s, and have since undergone dramatically rapid expansion. Nanomedicine is one of the important applications of nanotechnology. The development of smaller, less invasive, smarter, more precise, and more efficient medical devices is a fast-expanding global trend. The creation of specialized nanoparticles for use in medicine, such as magnetic nanoparticles and gold nanoshells, is advancing daily. This development is happening while nanomedicine is still in its early stages. As reported, superparamagnetic iron oxide nanoparticles are being used to specifically target and thermally destroy cancer cells without causing collateral damage to surrounding healthy cells and tissues.

Role of Artificial Intelligence in Medicine and Health Care

With the passing decades, Artificial Intelligence (AI) is gaining high popularity in various domains. In this chapter, we aim to present the current scenario of the application of AI in the field of medical science. Firstly, we will introduce the early and basic role of AI in the medical field. We preceded the chapter with a summary of the most current applications of AI in various areas of medicine and health care. In this review, we have discussed the latest developments of applications of AI in biomedicine while predicting the risk of disease. Estimating the success ratio of the therapy also manages or reduces the severity of complications, taking care of ongoing patients, living assistance, biomedical information processing, biomedical research, and medical imagining. We also present a survey on AI techniques, which were used by many authors with different objectives in medical science. Furthermore, we showcase the effects of the usage of AI by highlighting the reduction in the rate of mortality, and fast and accurate diagnostics which help in decreasing errors related to human fatigue and lessening medical costs. Finally, we draw attention to some of the possible weaknesses, apprehensions, and uncertainties in using AI in medical science. We briefly review the efforts being made to improve the healthcare industry by offering various AI-based healthcare products.

Absolute Images Reconstruction in Heart and Lungs for COVID-19 Patients using Multifrequencial Electrical Impedance Tomography System and D-Bar Method

Brazil is one of the countries most affected by the COVID-19 pandemic.

Since the beginning of November 2020, Brazil has been experiencing an acute crisis of

the disease, with an increase in cases, hospitalizations and deaths, including among the

youngest. During the month of April 2021, as intensive care units they were working

almost at full capacity throughout the country. Since the beginning of the pandemic, in

March 2020, without total, Brazil has reported more than 14 million cases of COVID-

19 and more than 400 thousand deaths. Due to the rapid spread of the virus and due to

the fact that the health systems of different countries are not prepared to serve the large

number of patients affected by this disease, we have proposed the use of

multifrequency electrical impedance tomography (MfEIT) in the management of

pulmonary disease in ICU beds. There are several other forms of tomographic imaging

that deliver better image resolution, however, MfEIT has some advantages over CT

Scan and X-rays, which are: the absence of ionizing radiation, the portability of the

equipment, the possibility of access remote control of the patient's clinical data by the

medical team, the visualization of dynamic pulmonary and cardiac parameters that are

not seen in computed tomography images, nor in ultrasound images. However, an

application of the D-Bar algorithms developed by Siltanen and his team, from 2012 to

2020, at the University of Helsinki, Finland, for viewing images in patients with

COVID-19 was evaluated. Various scenarios and criteria were proposed in the text and

the results obtained promising evidence for imaging internal organs in the radio

frequency range. As expected, codes cannot be considered in extremely low frequency

situations, as reconstructions are not considered. In the future, we seek to work with

deep neural networks to speed up the simulation of images and to compare results.

Muscular Dystrophies and Mitochondrial Myopathies

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

Updates on Childhood-Onset Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune, and multisystem disease. Childhood-onset SLE (cSLE) contributes up to 20% of all cases of SLE and refers to patients who develop the disease before their 18th anniversary. Impressive discoveries in all aspects of the disease emerge every day; one of the most interesting is whether cSLE is a single or a group of diseases, with diverse physiopathologic processes but sharing a rough phenotype. Patients with early onset disease (<5 years), with associated infections and severe disease manifestations, should urge the possibility of monogenic SLE, which represents a small proportion of all cSLE cases, but often with a more complicated clinical course. Despite its being considered a rare disease, the clinical outcomes could be devastating. Patients with cSLE had higher disease activity indexes than adults. Although the survival has improved, it also implies that patients remain a longer period under the effects of the disease. Enormous advances in the understanding of the physiopathological processes are helping to better diagnose children with lupus; still, we are distant to have a perfectly fitted therapy for all our patients. The outstanding efforts of clinicians and researchers to find new therapeutic strategies are encouraging. In this chapter, you will find a concise description of the novel advancements concerning the disease pathogenesis, classification, assessment of disease activity, treatment, and outcomes.

Introduction of Common Pediatric Diseases

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

New Approaches in P2Y12 Receptor Blocker Drugs Use

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

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

Hibernation or Transformation? Challenges in Cardiovascular Drug Development

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

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

Recent Advances in the Diagnosis and Management of Pulmonary Embolism

Acute pulmonary embolism (PE) is a form of venous thromboembolism

(VTE) and has varied clinical manifestations with significant morbidity and mortality.

The general population's overall incidence is on the rise due to the increasing

availability of D-dimer and computed tomographic pulmonary angiography. The

incidence is higher in males than females (58 versus 48 per 100,000, respectively),

increasing with age. In the United States, PE accounts for approximately 100,000

deaths annually. Specific populations, including patients with malignancy, pregnant

females, hospitalized medical and surgical patients, or patients with total joint

replacement, or arthroplasty, are at a higher risk for PE. Patients presenting with

hemodynamic compromise due to PE need to be treated with intravenous thrombolytic

therapy unless contraindicated, followed by anticoagulation. For over six decades,

traditional anticoagulants like unfractionated heparin (UFH) are used for short-term

anticoagulation. For patients who require long-term anticoagulation, low molecular

weight heparin (LMWH) like enoxaparin and a vitamin K antagonist like warfarin are

used to achieve therapeutic anticoagulation. Options for anticoagulation have been

expanding steadily over the last decade with the introduction of the first direct oral

anticoagulant (DOAC). Since their introduction, DOACs have changed the landscape

of anticoagulation. This narrative review aims to summarize for clinicians managing

pulmonary embolism (PE) the main recent advances in patient care, including risk

stratification, current data regarding the use of thrombolytic treatment, and direct oral

anticoagulants.

Cardiovascular and Renal Diseases in Systemic Lupus Erythematosus

Cardiovascular disease occurs in systemic lupus erythematosus (SLE).

Cardiovascular diseases are important in SLE. Cardiovascular diseases involve the

myocardium, pericardium, cardiac valves, and coronary arteries. Pericarditis is often

accompanied by pleurisy, tachycardia, and cardiac enlargement. Verrucae on the valve

leaflets cause a heart murmur. Myocarditis, coronary artery inflammation, and

pulmonary arterial hypertension may be seen. Lupus nephritis is the main cause of

renal damage in SLE. The kidney is the most important organ that determines the

prognosis of SLE. In this section, cardiovascular involvement in SLE is illustrated.

Developmental Toxicity of Aluminium and other Metals: Areas Unexplored

Reproduction and developmental damage has irreversible consequences compared to other body functions and may have adverse effects throughout life. In some circumstances, the damage passes from generation to generation. Many environmental agents contribute to developmental toxicities such as toxic metals, insecticides or pesticides, commercial or industrial pollutants, and air pollutants. Increased urbanization and industrialization have led to the accumulation of toxic metals in the environment. Widespread use of heavy metals in different fields such as agriculture, domestic, medical, industrial, and technological applications have resulted in increased exposure of heavy metals to the human population. Environmental exposure to heavy metals is extensively linked to toxic effects on mammalian embryos. Metals such as lead, cadmium, mercury and arsenic are known developmental toxicants that intensely affect fetal and embryonic development and cause certain malformations in developing embryo even at low concentrations. Other metals such as uranium, cobalt, lithium, Aluminium, manganese, and copper are also reported to induce developmental consequences, including neurobehavioral abnormalities, neural tube defects, fetal growth retardation, skeletal deformation, preterm or delayed birth, and still birth or postnatal death. Heavy metal developmental toxicity depends on different factors, including dose, duration, and route of exposure. Hence, heavy metals are known to be toxic to fetal and embryonic tissues and can produce serious teratogenicity in mammals; however, not much attention has been given to this topic. This chapter, therefore, summarizes the developmental toxicity of heavy metals on the mammalian system and their teratogenic mechanism in growing embryos.

Abdomen

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

Thoracic Surgery

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

Subject Index

Agents Used in the Treatment of Arrhythmias and Advanced Cardiovascular Life Support

Advanced Cardiovascular Life Support (ACLS) guidelines recommend certain drugs for hemodynamic stabilization, prevention of collapse, stabilization of a perfusing rhythm, improving peripheral resistance and cardiac output, and restoration of organ perfusion. It is known that no antiarrhythmic agent increases the percentage of patients discharged with good neurological status. For this reason, the commencement of medications and establishing vascular access should not delay high-quality CPR.

ACLS guidelines recommend drug adrenaline in the asystole algorithm and in those with cardiac arrest due to ventricular fibrillation (VF). For pulseless electrical activity (PEA)-related cardiac arrest, adrenaline and, in some cases, sodium bicarbonate is recommended. The drugs used in VF and pulseless VT (PVT) apart from adrenaline are vasopressin, amiodarone, lidocaine, esmolol, magnesium, and procainamide in selected situations. This chapter provides a brief outline of arrhythmias commonly encountered in routine clinical practice, together with principles of ACLS and indications and usage of resuscitative agents employed in these situations.

Supraventricular Arrhythmias and Their Management in the Emergency Setting: PSVT and AF

Supraventricular tachycardia (SVT) is a type of tachyarrhythmia with a narrow QRS complex and regular rhythm (heart rate >100 bpm). These patients are often symptomatic and present to the emergency department (ED) in acute attacks called paroxysmal SVT (PSVT). Most SVTs are regular rhythms. It starts suddenly with the reentry mechanism in the majority of patients. 60% of the patients have reentry with Atrioventricular (AV) node, and 20% have reentry via bypass pathways. Coronary artery disease, anginal chest pain and dyspnea occur in patients due to tachycardia. Heart failure and pulmonary edema may occur with left ventricular dysfunction. Vagal maneuvers and adenosine appear to be the treatments of choice for termination of stable SVT.

Aortic Diseases: Abdominal Aortic Aneurysm (AAA) and Dissecting Aortic Aneurysm (DAA)

Aneurysmal dilation is most common in the aorta, distal to the kidney vessels and proximal the iliac artery bifurcation. It is much more frequent in males than in females. It most commonly develops in middle aged and geriatric patients, patients with chronic HT, atherosclerosis, smoking history, and those with a genetic propensity for AAA, although none of this is an absolute rule.

The width of the aorta varies depending on the race, body area, gender and age, and the average aortic diameter is between 2.5 and 3.7 cm in general. Aortic diameter measuring 50% more (1.5 times) than expected is considered an aneurysm. If the diameter of the aorta is > 5 cm, the possibility of rupture increases and requires surgical intervention. In the abdominal aorta, which is generally located infrarenal,> 30 mm for both sexes is described as AAA.

In recent years, the term “Acute Aortic Syndrome” has also been used for all aortic emergencies. Signs and symptoms of AAA varies with the patient’s physiologic reserves, age and the extent of the disease with resultant organ damage (Table 1).

Heart Failure and Acute Pulmonary Edema (APEd)

Heart failure (HF) is a complex syndrome in which the cardiac output cannot meet the demand, i.e., metabolic needs of the tissues and reflect the impairment of the heart's pump function. This condition is also referred to as congestive heart failure (CHF) as it is mostly associated with fluid retention.

The four main factors that determine the pump function of the left ventricle, which are contractility (contractility), preload, afterload and heart rate.

Accepted guidelines divided patients with HF into three groups according to their left ventricular ejection fraction (EF). The group with a EF below 40% continues to be known as a “low/reduced EF” (HF-REF), and a group of 50% and above remains “preserved EF” (HF-PEF), while a group of 40–49% is at the border (mid-range), thus it was named mildly reduced EF” (HF-MREF). The incidence of HF-PEF increases with age. The majority of cases in the elderly is due to HF-PEF. Acute decompensated HF is a deadly cause of cardiac dysfunction that can present with acute respiratory distress. There are many different causes of APEd, though cardiogenic pulmonary edema is usually a result of acutely elevated cardiac filling pressures. Clinical findings develop as a result of impaired perfusion and/or venous distension, with resultant surge in pressure. The patient mostly present with progressive symptoms of HF or acutely appeared signs of left-sided decompensation.

Patients who are diagnosed with HF for the first time and who is admitted with APEd should be hospitalized and treated accordingly. HF develops in 10 to 20% of AMI cases. Since this group has a high mortality, it must be identified and treated. The main objective of the treatment in the Acute Left HF is to provide the respiratory and cardiovascular stability as soon as possible. The main goal is to “dry” the lungs, not just throwing off water.

COVID-19 pneumonia and respiratory distress can masquerade APEd in the pandemic period. Most “typical” radiological findings including ground-glass opacities are common in both entities. It is very frequent that a clinician mixes up the two entities, especially misinterpret APEd as COVID-19, because the outbreak affects so many people that every physician is conditioned to see the viral pneumonia. Therefore, educational resources should stress on how to implement correct differential diagnosis of cardiopulmonary entities including AHF/APEd in the pandemics in both hospital and outpatient conditions. This chapter provides a general overview of the diagnosis and management of HF and APEd with a special emphasis on the acute presentation in the pandemic era.

Chest Pain and Acute Coronary Syndromes (ACS)

Acute coronary syndromes (ACS), especially acute myocardial infarction (AMI), is the leading cause of death in the world. These represent damage to the cardiac myocytes in the setting of acute cessation of blood supply. Chest pain is a common presentation in patients with AMI; however, there are multiple non-cardiac causes of chest pain. The diagnosis cannot always be made based on the initial presentation. The emergent evaluation of a patient with probable ACS includes a careful assessment of history, risk factors and presenting signs and symptoms, de novo ECG abnormalities, and workup of cardiac troponins. Validated risk scores, such as HEART, TIMI, and GRACE, can be helpful in predicting outcomes and the likelihood of ACS in a patient with chest pain. ECG should be performed within 10 minutes of presentation. ST elevation MI (STEMI) is diagnosed with elevated ST segments in two consecutive leads on ECG. Likewise, elevated levels of cardiac troponins in the first hours of presentation are mostly a prerequisite for diagnosis.

Although cardiac catheterization is viewed as the standard diagnostic modality for coronary artery disease, exercise testing, stress studies, echocardiography, and coronary computed tomography angiography (CCTA) may be important adjuncts. Cardiac catheterization laboratory (CCL), coronary care units, EDs, EMS, and primary care institutions need to cooperate in unison to produce the best results for public health.

This chapter gives a brief outline of the diagnosis and management of ACS in the pandemic period.

Smart Nanomaterials for Cardiac Regeneration Therapy

Cardiovascular disease (CVDs) have been observed as the major cause of death worldwide. During the cardiac attack, the blood flow slows down, by which the pumping gets affected. For getting the heart functional, sometimes several surgeries are done that weakens the heart. In ultima cases, loss of heart cells led to a heart attack. The therapeutic options that are adapted for preventing CVDs patients are often being treated with invasive cardiac surgery. Lack of solution to heart troubles and its underlying mechanism led towards the drive of regeneration therapy. Tissue engineering and regenerative strategies goal serves a dual purpose, firstly to stop disease progression and secondly to reverse disease effects to regain and restore heart function. Nanotechnology has been a revolutionary step towards cardiac therapy. Through nanotechnology, there has been a great paradigm shift in the treatment of coronary heart diseases, heart injury, muscle cells improvement, normal functioning of the heart after massive injuries. Tissue-engineered therapeutics are basically delivered to the heart by two approaches, such as cardiac injections and cardiac patches. Engineered nanoparticles for the specific purpose of cardiac ailment play a vital role in heart cure and biomedical application.

Biomimetic Materials Design for Cardiac Tissue Regeneration

Globally, heart failure is among the principal cause of death. Heart transplantation is the only way out to replace the diseased or damaged heart. Since this technique has several disadvantages, newer therapeutic approaches are required for cardiac repair. One such approach is cardiac tissue engineering, which helps in designing and developing biomimetic materials that mimic the microenvironment of the myocardium. Approaches for cardiac tissue engineering consists of cell injection, tissue patch implantation, replacement of the valve, and injection of acellular materials. Biomaterials are designed to support stem cell expansion, protection, and differentiation. They also facilitate cell retention, cell survival and provide mechanical support. Advances in nanotechnology have made the biomimetic material design more advanced as it can deliver bioactive factors, manipulate surface topography, control cell behavior, and align cells and tissues properly. Furthermore, electrical conductivity and mechanical stiffness can be modulated as well. Overall, biomimetic materials are the new therapeutic approaches in the field of cardiac regenerative medicine, demonstrating their potential in treating heart disease.

Biomaterials for Cardiac Regeneration

Globally, cardiovascular disease is one of the predominant clinical conditions, which accounts for about 50% of human mortality and morbidity. No doubt pharmacological and surgical interventions have dramatically improved the quality of life of patients with cardiovascular diseases. However, the demand for new therapeutic interventions as well as regenerative strategies is currently increasing. Biomaterials, both natural and synthetic, have exhibited great potential in cardiac regenerative therapy. Therefore, the development of biomaterials based extracellular matrix, grafts or stents, etc. would be highly beneficial for supporting the natural function and physiology of heart tissues.

Role of Nanomedicine in the Diagnosis of Cardiovascular Diseases

Various lifestyle related factors are primarily responsible for the increase of cardiovascular diseases. The development of numerous diseases such as acute myocardial infarction, stroke and thrombosis need multiple therapies. These therapies are based on synthetic active ingredients, which in long-term usage, give adverse side effects. Currently, a lot of attention has been focused on nanotechnology based drug formulation, which can provide sustained drug release, increased half-life, and in turn, can circumvent limitations of conventional therapies. With the advent of the nanomedical approach, the survival length of the patients can be prolonged. This chapter mostly focuses on widely used nanomedicines in therapy and imaging of cardiovascular diseases.

Subject Index

Direct-acting Oral Anticoagulants in Liver Cirrhosis: What is the Current Status?

In the last few years, the coagulation abnormalities associated with liver cirrhosis were better characterized, concluding that the patients with liver cirrhosis are predisposed to thrombotic or bleeding complications. Portal vein thrombosis is the most frequent thrombotic event, associated with liver cirrhosis. Atrial fibrillation is also a frequent comorbidity in patients with liver cirrhosis associated with higher risks of embolic complications, needing an anticoagulant prophylactic treatment. Direct-acting oral anticoagulants (DOACs), warfarin, unfractionated heparin or low weight molecular heparin are not always efficient in liver cirrhosis. According to recent studies, DOACs are relatively safe in Child-Pugh class A or B liver cirrhosis for the treatment of acute portal vein thrombosis or prevention of embolic events in patients associating atrial fibrillation. All DOACs are contraindicated in patients with ChildPugh class C liver cirrhosis.

Clinical Biochemistry, Physiology & Genetic Disorders

A Final Thought

This final chapter in this book provides an overview of what is happening at the cutting edge of stem cell and regenerative medicine technology. It describes the research currently underway and how these technologies may have an impact on future clinical practice for all of us. Some of the ideas mentioned here will not be in the public domain, but they are all valid research projects.

The Outbreak of the Pandemic of Coronavirus Disease 2019 and its Impact on Medical Waste Management

Today, the global outbreak of the pandemic of coronavirus disease 2019 has the potential to wreak a serious impact on human health and to further trigger a global crisis. A great repercussion of this pandemic is occurring on sustainable medical waste management practices with a profound impact. On the one hand, medical waste management companies need to be ready to assist countries worldwide as they seek to manage the great volumes of infectious material; on the other hand, the use of gloves and face masks is increasing among population to stop the spread of the novel coronavirus. In addition to potentially being a biohazard, face masks and gloves can increase the plastic pollution if the disposal directions are not proper. Therefore, the current pandemic of the novel coronavirus poses new challenges regarding the management of medical waste practices above all for health measures for employees, proper waste treatment requirements.

The aim of this review is to collect data on the different systems and solutions implemented worldwide to manage municipal waste in the current situation.

Point-of-Care Portable In-vitro Diagnostics: Smartphones, Imaging, Sensing, Connectivity, and AI

Microfluidic-based (“lab-on-a-chip”) bioassays and sensors enable automated or simply-operated medical diagnostic testing in near real-time at almost any location. These diagnostic devices can be connected to networks, especially using smartphones, where the smartphone camera serves as an optical detector or means of image capture. In addition, the smartphone provides connected sensors, GPS, visual displays, user-friendly interfaces, and limited electrical power. The added communications, control, and computational capabilities foster a synergism that will widen the applications of POC devices in healthcare and facilitate data acquisition for machine learning and artificial intelligence to enhance diagnostics accuracy and expand medical knowledge. Here the technological developments for microfluidic devices in combination with consumer devices, such as smartphones, for integration into the Internet of Medical Things (IoMT), are reviewed.

Effects of Microenvironment Factors on Angiogenesis

Angiogenesis is a vital step for complete organ engineering, and the microenvironment is one of the four basic elements of tissue engineering. Microenvironment factors such as oxygen content and stress are key dynamic factors that can trigger the variations of angiogenesis. We may induce the formation of beneficial blood vessels and prevent the formation of pathological blood vessels by precisely regulating the microenvironment. In this chapter, we will elaborate the interaction between vascular endothelial cells and the extracellular microenvironment and summarize the influence of various microenvironment factors on angiogenesis. The finding that microenvironment factors play such a concerted role in angiogenesis suggests that incorporating microenvironment factors into tissue engineering might accelerate the development of novel therapeutics.

Traditional Medicine Based Cardiovascular Therapeutics

Cardiovascular diseases continue being the major cause of death worldwide, despite the constant and consistent efforts made towards the management and control of coronary artery diseases. These diseases are resulted by the metabolic imbalance involving elevated energy requirements and deficient oxygen supply to the cardiac myocytes, ultimately leading to myocardial necrosis. These diseases are closely associated with several changes in metabolic and signaling pathways that involve increased oxidative stress, excessive cytoplasmic and mitochondrial calcification, elevated lipid peroxidation, disturbed antioxidant homeostasis, dynamic cellular metabolism, irreversible DNA damage, and other pathophysiological alterations. The mechanism of pharmacological action demonstrated by modern western medicines usually adopt the lock-and-key model that involves the action of a principle therapeutic agent onto a specific and selective target to regulate a prime metabolic and signaling pathway, therefore becoming unsuitable to treat the disorders mediated by multiple molecular pathways. The side-effects associated with the use of such synthetic drugs are also an alarming health concern. The traditional system of medicine applies multiple natural ingredients that contain several active metabolites, therefore imparting a holistic pharmacological effect on multiple targets that orchestrate multiple pathways, without eliciting significant side-effects. This book chapter reviews various Indian and Chinese polyherbal formulations designed and developed according to the traditional system of medicine, which have been appropriately formulated and adequately characterized in-vitro, in-vivo, and in-silico following the stipulated scientific standards and medical regulations. Significant emphasis is also laid to review the informatic branches and cellular models available to evaluate and assess the pharmacology and toxicology of such polyherbal formulations.

Parkinson Disease and Antiparkinsonian Drugs

This chapter is a comprehensive account of Parkinson's disease and the medicinal chemistry of antiparkinsonian drugs. It provides the mechanism of disease progression and drug action and detail structure-activity relationships of the antiparkinsonian drugs to give the knowledge base for pharmacists. After a study of this chapter, students will be able to:

• Discuss the epidemiology and etiology of Parkinson disease (PD)

• Describe the clinical features of idiopathic PD and differentiate between cardinal motor features and non-motor symptoms

• Discuss various risk factors and corresponding mechanisms responsible for the development of PD symptoms

• Review biosynthesis of dopamine, its metabolic outcomes, dopaminergic pathways, receptor distribution and corresponding signal transduction mechanisms

• Explain in detail the pathophysiologic mechanisms responsible for the clinical features of idiopathic PD

• Evaluate the clinical role of L-DOPA and discuss its mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications and precautions

• For each medication class listed below, discuss their mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications and precautions

o Dopamine agonists

▪ ropinirole (Requip®, Requip® XL); pramipexole Mirapex®, Mirapex® ER); rotigotine transdermal patch (Neupro®), and apomorphine (Apokyn®)

o Catechol-O-methyltransferase (COMT) inhibitors

▪ entacapone (Comtan®) and tolcapone (Tasmar®)

o Selective monoamine oxidase-B (MAO- B) inhibitors

▪ selegiline (Eldepryl® and Zelapar® ODT) and rasagiline (Azilect®)

▪ amantadine (Symmetrel®)

o Anticholinergic agents (benztropine (Cogentin®) and trihexyphenidyl)

Subject Index

Newer Technologies in Cardiovascular Disease Detection and Management

Cardiovascular diseases cause mortality and morbidity worldwide. The progression of cardiovascular disease is associated with several risk factors which include hypertension, diabetes mellitus, obesity, stress, kidney disease, smoking and alcohol increase the risk of developing cardiovascular complications. The newer health care technologies in the cardiovascular disease prevention include sensor devices, webbased strategies, smart phone applications, telemedicine; text message based mobile applications, stem cell therapy, robotic sleeve, artificial intelligence algorithms, big data technology, voice technologies, block chain technology, bioresorbable stents, leadless pacemaker, chatbots technology are used to prevent the progression of cardiovascular disease. The cardiovascular diseases are imposing huge health care expenditure burden on patients and their families. Health care innovations deal with the application of ideas, procedures, and novel concepts designed to promotes benefits to society. Advance health care information technologies are useful for the detection of cardiovascular disease risk at the earlier stages to provide better health care interventions to improve their quality of life. The innovative technologies are boosting the advances in cardiovascular health care. The novel health care technologies should focus on developing new innovations for improving the quality of patient care services in hospitals.

Rheumatic Heart Disease

The cardiovascular disease affects the heart, blood vessels and blood circulation cause death in adult patients. The cardiovascular diseases include ischemic heart disease, congestive heart failure, hypertension, angina pectoris, stroke, peripheral vascular disease can develop due to a low level of blood flow to the heart can increase the risk of cardiovascular complications. Rheumatic fever is an autoimmune inflammatory disease which can develop with infectious species like bacteria, fungi, virus creates inflammatory conditions and results in the origin of inflammatory mechanisms in the body. It occurs, when the immune system responds abnormally to the inflammation with slow deposition of the calcium crystals in the heart valves increase the risk of developing rheumatic heart disease. Currently, the high prevalence of rheumatic heart disease occurred from low and middle-income countries. Ineffective control of rheumatic fever damages several vital organs such as the heart, brain, kidney, and lungs. The blood test, electrocardiogram, chest x-ray, echocardiogram, cardiac MRI scan, treadmill test, coronary angiogram test can determine the cardiovascular risk. The clinical management of rheumatic heart disease with prescribing antibiotics, anti-inflammatory drugs, and corticosteroids are used to reduce the inflammation and also minimizes the progression of cardiovascular damage.

Cardiomyopathy

Dilated cardiomyopathy is a heart muscle disease that occurs due to dilation and dysfunction of ventricles. The proper understanding of etiology, pathogenesis can help with determining better therapeutic options for the management of disease complications. The various types of cardiomyopathy include restrictive cardiomyopathy, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy. Diabetes mellitus, genetic conditions, high blood pressure, heart attack, palpitations, heart valve defects, and pregnancy, smoking, alcohol, and connective tissue disorders are well known risk factors for the development of cardiomyopathy. The clinical manifestations of cardiomyopathy include palpitations, dizziness, headache, chest pain, shortness of breath and edema. The electrocardiogram, chest x-ray, echocardiogram, treadmill test, coronary angiogram test can determine the cardiovascular risk. The clinical management of cardiomyopathy with the prescribing pattern of beta blockers, angiotensin-converting enzyme inhibitors, diuretics, digoxin, angiotensin II receptor blockers, anti-platelet medications can minimize the development of cardiomyopathy complications.

Inflammatory Heart Disease

The inflammation of the heart muscles is caused by the virus, fungi, bacteria, food, smoke, air, and parasites that increase the inflammatory conditions in the heart muscles known as inflammatory heart disease. Endocarditis is an infection that occurs in the inner lining of the heart valves. Endocarditis commonly occurs by the bacteria, fungi or other microbial species present in the body, reaches the blood stream and leads to damaging the heart. Myocarditis is an inflammation of the myocardium which is present in the middle layer of the heart. It is caused by a viral species infection. The clinical manifestations of the myocarditis include chest pain, fatigue, edema, breathlessness, joint pain, fever, weakness, palpitations and abnormal heart rhythms. Pericarditis is a clinical condition in which the cell membrane around the heart is inflamed. The more amount of fluid deposit around the heart may increase the risk of inflammation and causes pericarditis. The electrocardiogram, chest x-ray, echocardiogram, treadmill test; coronary angiogram test can determine the severity of cardiovascular disease. The management of inflammatory heart disease includes antibiotics, corticosteroids, antiplatelets, diuretics, angiotensin converting enzyme inhibitors, and beta blockers control the progression of inflammatory situations associated with the heart.

Congenital Heart Defects

Congenital heart disease is congenital anomalies that having heart defects origin form the birth. The structural abnormality of the heart, great vessels is diagnosed at the time of birth. It affects childbirth during pregnancy. Congenital heart defects change the blood flow to the heart. The defect ranges from mild to severe clinical symptoms that can lead to developing life-threatening conditions. The progression of congenital heart disease associated with genetic and non-genetic factors. The risk factors for include diabetes mellitus, viral infections, medications like ACE inhibitors, drinking alcohol and smoking during pregnancy, genetics may increase the more health care burden to diagnosed patients. The improper treatment of congenital heart defects can lead to the development of heart failure, cyanosis, stroke, and arrhythmia. The clinical symptoms of congenital heart defects include shortness of breath, chest pain, cyanosis, rapid heartbeat, cardiac murmur, edema can elevate the risk of heart defects. Physical examination of the patient, echocardiographic investigations are useful for the detection of heart defects. Effective prescribing pattern of ace inhibitors, arrhythmias, beta blockers, antiplatelet, and diuretics is used to enhance health condition of the patients.

Cardiac Arrhythmia

The heart conduction and contraction provide the driving force for the pumping of blood to the heart. The abnormalities in the conduction properties of the heart can lead to arrhythmias. The action potential helps the opening and closing of the ion channels that cause conduction of the cardiac muscles. Atrial fibrillation is most commonly occurs in the cardiac arrhythmia. The arrhythmia prevalence has an incidence of 1%, it is an aging dependent factor and the incidence was raise to ≥2.5- fold by the year 2050. Elderly patients the progression of the atrial flutter is related to cardiac disorders. The clinical symptoms of atrial flutter include anxiety, palpitations, dizziness, headache, irregular heartbeat that can impair the quality of life of the patients. The defects in cardiac rhythm are associated with a significant rise in health care cost and also mortality among the affected population. Ventricular arrhythmias are causing about 75% to 80% of the cardiac deaths annually in the world. The ECG devices, echocardiogram, doppler studies, stress test, holter monitoring test are used to identify the risk of developing cardiac arrhythmias among arrhythmias patients. Currently, one third of the patient’s exhibit an absence of arrhythmia symptoms and patients were not aware of abnormal heart rhythm. Therefore timely detection of clinical symptoms and prescribing better therapeutic approaches may improve the quality of the patients.

Aortic Aneurysm

The weakening of the artery causes abnormal bulging and rupture of the artery with bleeding results in the development of an aneurysm. An aneurysm occurs in the various vital organs in the body which include the brain, aorta, legs, and spleen. Patients with age more than 60 years, hypertension, smoking, can drastically increase the risk of the aortic aneurysm. The development of aneurysm rupture is influenced by the aneurysm size, expansion rate, and uncontrolled hypertension increases the risk of more bleeding in the arteries. The arteries of brain cells and heart are the most common sites of developing serious aneurysm complications. The incidence of abdominal aortic aneurysms has been increasing from the past few decades. The aortic aneurysm has an incidence of 5-10 cases per 100,000 was seen in more than the age of 60 years. An aneurysm is detected with a computed tomography scan, magnetic resonance image scan, ultrasonography, angiography examinations helpful for detecting the abnormalities in the arteries. The prevention and management of aneurysm through lifestyle modification practices, eating a healthy diet, stress management, regular medication adherence and maintaining controlled levels of risk factors could minimize the future complications of an aneurysm in primary care settings.

Deep Vein Thrombosis

Deep vein thrombosis is a serious health problem due to thrombosis in the systemic circulation. Ineffective treatment of deep vein thrombosis increases the risk of pulmonary embolism. Venous thrombosis condition decreases the blood flow to the veins in the legs. Valves help to promote the blood flow to the veins, during the hypoxia condition the low level of the blood flow to the veins can manifest the symptoms of venous thrombosis. The incidence of deep vein thrombosis is estimated to one patient per 1000 cases annually. The clinical manifestations of venous thromboembolism include swelling; redness can increase the progression of venous thromboembolism. The blood test, doppler ultra sound, venogram and magnetic resonance imaging test are helpful for the detection of deep vein thrombosis. The pharmacological and non-pharmacological treatment modalities are encouraged in the inpatient and outpatient wards could useful for reducing the progression of disease complications.

Heart Valve Disease

Valvular heart disease occurs by the defects in tricuspid, aortic, mitral, pulmonary artery leads to develop heart valve abnormalities. Gender, age, hypertension, diabetes mellitus, alcohol, smoking and hypercholesterolemia can contribute to the progression of valvular heart disease. Previous research studies stated that one-third of elderly patients echocardiographic examination showed that the evidence of calcific aortic valve sclerosis. Patients with age more than 60 years suffer from the calcific aortic stenosis. It is more prevalent in western countries as compared with other cardiovascular diseases such as coronary artery disease, angina pectoris, myocardial infarction, and hypertension. Previous research studies demonstrated that 40 million people are affected by the age group of 65 years in the 2010 year and expected to rise 55 million in 2020 and 72 million in 2030. Patients with clinical signs of aortic stenosis during the physical examination should undergo various other examinations like chest x-ray, electrocardiogram, and echocardiogram useful for the detection of valvular heart disease risk at the early stages. Aortic valve replacement is used to lower the progression of aortic stenosis among high-risk patients.

Diagnostic Investigations for Detection of Cardiovascular Diseases

Cardiovascular diseases are a group of disorders of the cardiovascular system which include coronary heart disease, hypertension, myocardial infarction, angina pectoris, rheumatic heart disease, and stroke etc. Currently, cardiovascular diseases are causing 21.9 percent of total deaths globally and that will rise to 26.3 percent by 2030. The risk factors for cardiovascular disease include hypertension, stress, alcohol, diabetes mellitus, smoking, and obesity which highly impact the development of cardiovascular disease. The cardiovascular disease diagnostic test includes electrocardiogram, echocardiography, MRI scan, CT scan, treadmill test, Doppler studies and coronary angiography tests which are vital for determining the severity of cardiovascular disease among diagnosed patients. Early detection of cardiovascular disease risk factors and regular cardiovascular disease risk screening modalities can lower the alarming incidences of cardiovascular diseases in health care settings.

Introduction to Heart Anatomy and Physiology

The cardiac system represents the heart and blood vessels. The blood is distributed to multiple organs present in the body. Capillaries are minute blood vessels, allow the gas exchange processes. Veins send blood to the heart from the capillaries. The heart is situated in the thorax, posterior to the sternum and superior surface of the diaphragm. The heart has four chambers, and two atria above and two ventricles below. The oxygenated blood moves to left portion of the heart and enters into the left atria and ventricle. The deoxygenated blood pumped into the right side of the heart and moves into the right ventricle and flows towards the lungs. The heart is covered with three protective layers which include an epicardium, myocardium, and endocardium. The cardiac physiological functions are controlled by a group of electrical impulses. The electrical impulse origin from the sinoatrial node and located on the top side of the right atrium. It causes atria muscle contractions and thereby sends blood into the ventricles. A cardiac cell demonstrated the electrical activity and transmits the cardiac impulses to the heart to maintain the normal heart beating and initiation of the cardiac cycle. The cardiac event causes the opening and closing of valves results in contraction and relaxation of cardiac chambers. The cardiac cycle consists of systole and diastole events, during the systole, ventricles contract and send blood to arteries and during diastole, the ventricle relaxes and collects blood from atria. The electrical activity of the heart originates from SA node and causes atria to initiate contraction of cardiac muscles and supply of blood into the ventricles.

Meat Curing and Preservation Methods

Salting is one of the oldest food preserving methods. New salting methods for meat products are currently being studied aiming at reducing process time and labour costs, increasing process yield, and producing safe, low-salt content foods with acceptable sensory characteristics. In this context, ultrasound, high hydrostatic pressure and microwave technologies have been highlighted. Several manuscripts have addressed this theme and the results were satisfactory, urging the need for further studies in order to improve and enable the use of such methods. This chapter will cover traditional salting methods and new ones, currently being discussed aiming at improving the quality and yield of products.

Transmission Electron Microscopy: Theory and Applications

Transmission Electron Microscopy (TEM) is a useful technique to explore the molecular structure, interactions and processes including structure-function relationships at cellular level using a variety of TEM techniques with resolution of one angstrom (Ǻ) 1 to 1000 Ǻ. Developments in modern science and technology, especially in the material science, depend significantly on microstructure characterization. In this context, novel characterization techniques are crucial to understand the properties of materials. The quality of TEM results is dependent on preparation of TEM grid. Experts are constantly working on optimization of milling parameters to reduce the potential artifacts. The resolution power of TEM makes it possible to visualize different objects with high quality images to study complex structures and tissue morphology. Thus, TEM has made a milestone towards the understating of cellular structure. This chapter includes introduction and theory of TEM including its instrumentation, sample preparation, and working applications.

Antimicrobial Materials and Devices for Biomedical Applications

Bioaccumulation in sanitary devices, caused by opportunistic pathogens, intervenes negatively in the recovery of a patient since these are able to provoke a mild or life-threatening infection. Thus, surfaces of certain materials such as gauzes, catheters, sutures, etc., which are adjacent or directly exposed to a healing zone, are prone to become sites for the growth, proliferation, and spread of pathogenic microorganisms. Although in surgical or healing processes, sterile materials are usually applied, the time of contact with biological interfaces is long enough to make the sterilization but not enough to control and prevent an infection since pathogens abound in the surroundings. Air, water, and soil can be potential vectors, without considering those factors related to iatrogenesis that also play a role in the opportunities for the patient's recovery. Within this context, engineered materials are currently being developed and explored towards devices and biomaterials with improved design, performance, duration, biocompatibility aiming to be safer for the user. The surface functionalization of materials with antimicrobial agents is a highlighted alternative to overcome this issue. This chapter addresses current antimicrobial materials, as well as strategies for obtaining antimicrobial surfaces and coating as well as their properties. In addition, the safety assessment of biomedical applications and international standards are discussed.

Necropsy in Reptiles

In this chapter, we describe the method of necropsy in wild reptiles, offering some information regarding the different orders and anatomic characteristics of determined species.

Necropsy in Wild Mammals

In this chapter, we describe the method of necropsy in wild mammals, offering some information regarding the different orders and anatomic characteristics of the determined species.

Necropsy in Wild Birds

In this chapter, we describe the method of necropsy in wild birds, offering some information regarding the different orders and anatomic characteristics of determining species.

Subject Index

Postnatal Surgical Approach of Congenital Heart Disease

The advances in neonatal care and pediatric cardiac surgery have allowed repairing of complex congenital heart disease in the newborn and young infants with excellent results. The most common congenital heart defects that may need early surgical treatment are tetralogy of Fallot (TOF), transposition of the great arteries (TGA), univentricular heart, total anomalous pulmonary veins connection, hypoplastic left heart syndrome, critical aortic stenosis, and truncus arteriosus. TGA, characterized by atrioventricular concordance with ventriculoarterial discordance, is the most common cyanogenic cardiopathy, which requires treatment in the neonatal period. Atrioseptostomy with Raskind balloon must be performed in the newborn with TGA, who presents significant hypoxia and restrictive atrial septal defect. Surgical treatment of TGA depends on the gestational age diagnosis, associated defects and evaluation of the left ventricle anatomy and function. TOF is the cyanogenic cardiopathy that requires therapy more frequently within the first year of life. Those newborns with TOF who present severe cyanoses and or hypoxic crises may become ductus dependent, requiring surgical shunting procedure, percutaneous ductal stenting or total repair. Currently, there is a trend to perform neonatal total surgical repair in the centers of excellence, based in the low surgical risk. In univentricular hearts, medical decision depends on some anatomical aspects. While in case of significant pulmonary flow obstruction, it will require shunting procedure, in case of pulmonary overflow, it may need pulmonary banding. Total anomalous pulmonary venous return, critical aortic valve stenosis, and pulmonary atresia patients will require surgical or interventional heart catheterization procedures as a newborn. While, newborns with Ebstein’s anomaly have about 60% chance of requiring early surgical intervention.

Clinical Management of Congenital Heart Diseases in Neonates

Management strategies for congenital heart disease (CHD) in the neonate have evolved significantly. Advances in surgical technique, medical technology, and perioperative care have resulted in excellent post-repair survival, even for complex types of CHD. Furthermore, with the increased availability and accuracy of prenatal diagnosis by fetal echocardiography, the postnatal management of these newborns can often be anticipated and planned. The prenatal diagnosis of CHD has been associated with decreased morbidity and mortality for some forms of major CHD. As most cases of major CHD are not identified prenatally, clinical examination of the newborn and pulse oximetry are also important means of identifying additional cases. In summary, to improve the outcomes of a neonate with CHD, surgical repair or catheter intervention may be offered. For this purpose, early recognition of a neonate with CHD is necessary for stabilization and timely intervention.

Fetal Cardiac Intervention

Fetal heart interventions have been developed for select cardiac defects in order to alter the natural history of disease and improve patients´ outcomes. Intervention rationale and patient selection criteria, as well as associated risks and procedural technical considerations have been reviewed. Fetal aortic valvuloplasty is performed in fetuses with severe aortic stenosis with evolving hypoplastic left heart syndrome, with improving rates of biventricular outcome and early survival; and in rare cases of fetuses with aortic stenosis with severe mitral insufficiency and restrictive foramen ovale. Fetal atrial septoplasty with atrial septal stent placement in patients with hypoplastic left heart syndrome with intact or highly restrictive atrial septum has not yet demonstrated a decrease in the disease´s associated mortality. There is limited data regarding the results of fetal pulmonary valvuloplasty in fetuses with pulmonary atresia with intact ventricular septum with evolving hypoplastic right ventricle. Pericardiocentesis for severe pericardial effusion secondary to heart tumors or a cardiac diverticulum or aneurysm continues to be a rare procedure in an exceptional condition. Key aspects regarding selection criteria for intervention and technical and clinical results, require further study in a multicenter collaborative approach.

Labor Management of Pregnant Women with Fetuses with Congenital Heart Diseases

Congenital heart defects (CHDs) are the most common defects at birth. Thus, their prenatal diagnosis is extremely important, since early intervention, when required, dramatically reduces newborn mortality. CHDs, that occur both at the intrauterine phase and during the first hours of life, are well tolerated and do not require specialized care during delivery. However, some severe CHDs have an increased risk of hemodynamic instability and may require maintenance of fetal shunts after birth. In these cases, planning the time of delivery and selecting a tertiary hospital are necessary. In some cases, there may be maternal or fetal indications to anticipate delivery, including a variety of obstetric ones. Thus, the birth of a newborn with CHD is a multidisciplinary event, involving obstetricians, neonatologists, and cardiologists.

Environmental Factors Associated with Congenital Heart Diseases

Congenital heart diseases (CHD) are common, of largely unknown etiology, with high mortality. This chapter presents the available information on environmental factors that may alter the risk for CHD. Information regarding parental characteristics and conditions, maternal therapeutic drug exposures, parental nontherapeutic drug exposures, and environmental exposures are presented. Aside from some cardiac teratogens and prenatal maternal conditions or exposures associated with an increased risk for CHD, such as thalidomide, and retinoids, smoking, maternal rubella infection, phenylketonuria, hypertension, and diabetes, studies investigating most of environmental risk factors have yielded conflicting results. Associations were found for febrile illness, in vitro fertilization, stressful life events, hyperhomocysteinemia, obesity, hypertension, antihypertensives, bronchodilators, anticonvulsant drugs, nontherapeutic drugs, alcohol, air pollution, disinfectant products, pesticides, solvents, metals and landfill/hazardous waste sites. Some principles for prevention can be useful, as preconception and prenatal care with specific attention to the intake of folic acid, vaccination for rubella, detection and effective management of phenylketonuria, hypertension, and diabetes, discussion of any medicine use, avoidance of infections and chemical exposures, alcohol, smoking, and non-therapeutic drugs. Women receiving therapeutic drugs should be regularly monitored. In addition, screening for CHD should be performed when environmental risk factors are present. Further investigations for the development of prevention and intervention are needed.

Genetics and Congenital Heart Disease

Congenital defects are frequent, occurring in 2-3% of live births, with high morbidity and mortality. Congenital heart defects are the most frequent, occurring in 1% of all live births. Most occur as isolated malformations, but approximately 1/3 are part of a syndrome, usually of genetic etiology. The correct etiological diagnosis is important for useful clinical follow-up and genetic counseling. Children born with congenital heart defects should be carefully examined for other malformations and dysmorphia.

Extra Cardiac Defects in Fetuses with Congenital Heart Diseases

Extracardiac malformations (ECMs) and chromosomal abnormalities are common in fetuses with some congenital heart defects (CHD). The frequency and type of ECMs and chromosomal abnormalities vary according to the type of CHD and the studied population. The detection rate of CHD and ECMs depends on the first-trimester screening through nuchal translucence (NT) measurement, second trimester anomaly scan, and fetal echocardiography. The CHDs most frequently associated with ECMs are atrioventricular septal defect (AVSD), ventricular septal defect (VSD), tetralogy of Fallot (TOF), hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA), aortic arch, coarctation of the aorta (CoA) and interruption of the aortic arch (IAA). Conversely, the association of ECMs and chromosomal abnormalities with the transposition of the great arteries (TGA) is low. CHD such as: Ebstein's anomaly, left ventricular outflow tract obstruction (aortic stenosis) and obstruction of the right ventricular outflow tract (atresia and pulmonary stenosis) are associated with extremely low ECMs and chromosomal abnormalities, and are limited to a few sporadic cases.

Heart Failure in Fetuses

Fetal echocardiography began in the late 1970’s with the development of ultrasound imaging and has progressed to be able to make the diagnosis of many forms of structural and functional congenital heart disease. Coupled with the pulsed and color Doppler technique, echocardiography has made advances in determining the prognosis of individual fetuses in utero. The assessment of fetal cardiac function in fetuses continues to evolve including many markers of poor prognosis in the fetus. A tool for this clinical diagnosis is the Cardiovascular Profile Score. This score has become the “heart failure score” and combines echo markers of fetal cardiovascular functional deficits that have been correlated with perinatal mortality. The goal of this score is to detect signs of heart failure before they progress to non-immune-hydrops fetalis. The fetus with hydrops from noncardiac causes may improve spontaneously, or progress to develop heart failure and the score can be used in the early assessment of this fetal clinical picture development. This chapter presents the CVP score for use in fetuses who appear to have heart failure.

Fetal Cardiac Dysfunction Related to Extracardiac Conditions

The main function of the heart is to provide an adequate perfusion to the different organs. This function is achieved through an adequate filling of the ventricles from the atria (diastole) and the subsequent contraction of the muscular walls in order to generate a sufficient pressure to eject blood from the ventricles into the aorta and pulmonary artery (systole). The inability of the heart to provide sufficient perfusion the body tissues is defined as “heart failure”. In the fetus, heart failure is usually a late event characterized by cardiomegaly, atrioventricular regurgitation and fetal hydrops that occur after a subclinical period of cardiac dysfunction when the heart tries to adapt to the initial stages of an insult through cardiac remodelling. Different cardiac and extra-cardiac conditions can lead to fetal cardiac dysfunction and cardiac failure in utero. Intrinsic cardiac conditions potentially leading to heart failures include cardiomyopathies, structural abnormalities and persistent arrhythmias, while extrinsic causes comprise extra-cardiac lesions that contribute to heart failure through high output states, increased afterload, or cardiac compression resulting in low cardiac output and increased central venous pressures. The aim of this chapter is to provide an up-to-date on the causes, physiopathology, prenatal diagnosis and clinical implications of the most common extra-cardiac conditions potentially leading to fetal heart dysfunction.

Premature Closure of the Foramen Ovale and the Ductus Arteriosus

The foramen ovale and the ductus arteriosus are fetal circulation shunt sites, and the appropriate flow profile in these shunts allows the maintenance of fetal hemodynamic stability. The presence of restrictive or closed foramen ovale and/or ductus arteriosus may lead to poor fetal outcomes, such as right ventricular failure, neonatal pulmonary hypertension, or even death. Fetal echocardiography is the main tool for the diagnosis and assessment of premature closure of the foramen ovale and/or ductus arteriosus, and its intrauterine and/or postnatal management. In some cases, fetal intervention or soon after birth may be required in the presence of fetal hemodynamic instability.

Fetal Cardiac Tumors

Fetal cardiac tumors (FCT) are rare anomalies (about 1% among prenatal cardiac problems). There are more frequent multiple FCT and less frequent single FCT. The FCT occur in the population of healthy young mothers and risk factors are not easily detectable, but environmental factors (benzapirin?) could play a role. Basic ultrasound (US) anatomy in the 1st and 2nd trimester usually is normal and FCT are usually detected in the second half of pregnancy. In the majority of cases the fetus’s growth is normal. In each case, targeted fetal echocardiography should be performed in a fetal cardiology center. The very first problem is to discriminate between normal heart anatomy and congenital heart defect. The second goal of fetal echocardiography in FCT is to make an assessment of the hemodynamic status of the fetus. Extracardiac and additional anomalies coexisting in cases of FTC can be divided into two types i.e., frequent and rare. An experienced fetal cardiologist can not only make a proper diagnosis but also should counsel parents about the short-term prognosis for the fetus (about his future during prenatal life) as well as long term prognosis (after birth and later on). In cases of maternal decision to continue the pregnancy, fetal echocardiography monitoring should be offered to evaluate possible hemodynamic changes, to prepare both fetus and pregnant woman for optimal time for delivery and perinatal care. The main goal would be to avoid prematurity and to confirm fetal wellbeing, despite the cardiac abnormality. Details of echocardiography and postnatal outcome are presented in rhabdomyoma, teratoma, fibroma, myxoma and hemangioma. The way of delivery in surgical resection of cardiac tumors in newborns is discussed. In differential diagnosis, “bright spot” is discussed. Suggested management – algorithm of perinatal care in cases of FCT is presented with emphasis on cooperation of a perinatal team. FCT can be diagnosed at 20 weeks of pregnancy, which allows to start echocardiographic monitoring, taking into consideration the potential risk of hemodynamic progression. FCT (both multiple and single) can be the first sign of tuberous sclerosis complex in later prenatal or postnatal life. Single FCT other than rhabdomyoma can be asymptomatic in newborns, but may require an early surgical resection, therefore delivery in tertiary centers is recommended. FCT are a good example of the practical value of prenatal cardiology development.

Fetal Myocardial and Pericardial Diseases

This chapter provides an overview of the most frequent pathologies of the myocardium and pericardium during fetal life. Considering that some of these pathologies constitute a group of uncommon conditions, they are of interest from the point of view of their prognostic and therapeutic value. Besides, they are also within the most striking pathologies found in the screening of the fetal heart, and the ones which cause greater anxiety in the family and professional environment. Progress has been made in different diagnostic techniques, outlining some therapeutic advancements, as well as in the importance of new technologies that allow to deepen our knowledge of the functional defects of the cardiac muscle during fetal life.

Fetal Ventricular Inflow Anomalies

Congenital heart diseases (CHDs) are largely known as an important cause of fetal perinatal mortality. Currently, the accuracy of fetal echocardiography enables the detailed diagnosis of a significant variety of congenital cardiac anomalies, and it has also been demonstrated that prenatal outcomes may improve in critical CHDs. Accordingly, this chapter provides a detailed overview of the important anatomic aspects of some of the ventricular inflow anomalies, focusing on currently available information, to enable the prenatal diagnosis of such CHDs by ultrasound or echocardiography. Information regarding prenatal management, delivery plan strategies, and differential diagnosis of such anomalies is presented. The chapter also discusses the parental counseling and fetal and neonatal therapeutic management of such congenital cardiac anomalies. Univentricular atrioventricular (AV) connections, straddling and overriding of AV valves, and crisscross hearts are described in the current chapter. The concept of “functionally single ventricle” encompasses a group of CHDs in which the dominant ventricular chamber is responsible for maintaining the systemic and pulmonary circulations and not suitable for a biventricular repair. The central feature of such hearts is the univentricular AV connection. Regarding the type of the straddling of an inlet valve, it is based on the insertion of the tension apparatus of the AV valve into the crest of the ventricular septum or in the contralateral ventricle. Meanwhile, overriding of an inlet valve is related to the annulus of the AV valve and may interfere in the AV connection. Depending on the degree of the overriding of the straddled valve, the ventricles are in a dominant and rudimentary relationship, and a double-inlet AV connection, primarily the double-inlet left ventricle is the most frequent type of AV connection. In general, straddling and overriding of an AV valve requires a ventricular septal defect, and straddling may occur alone or in the presence of an overriding. In “crisscross” hearts, the ventricular inlet flows are in a cross shape and the ventricles are arranged in a superoinferior relationship. During an ultrasound examination, the crossed AV valves produce false images of the mitral valve or tricuspid atresia in a standard 4-chamber view, which makes the diagnosis difficult. In fact, the knowledge about the detailed anatomy, the assessment of the ventricular outflow tracts, and the identification of other possible associated cardiac anomalies are important for improving In Utero and postnatal management in ventricular inlet anomalies described in the current chapter.