bluuebunny/crossref_metadata_2025 huggingface dataset:
Networks in the Lamprey Optic Tectum
Authors: Kardamakis Andreas A. , Pérez-Fernández Juan , Grillner Sten
Published: May 2019

Critical to survival is the rapid detection and processing of events, registered by our senses, for the selection of an appropriate motor action. One essential task is to select or prioritize which of the many stimuli is most important for gaze reorientation. In vertebrates, parts of this sensorimotor task are solved by a dorsal mesencephalic region called the optic tectum (OT), also known as the superior colliculus (SC) in mammals. This structure receives direct afferent multisensory inputs, but also indirect cognitive and other nonsensory modulatory inputs from forebrain areas used to bias tectal activity. These inputs interact with the intrinsic tectal circuitry to select orientin or evasive behavior. This chapter explores the phylogenetic conservation of the OT and its connectivity pattern in an accessible and reductionist vertebrate animal model, the lamprey, to develop preparations that allow for isolating components of this sensorimotor process while evaluating their impact on goal-directed behavior.
The Crustacean Stomatogastric Nervous System
Authors: Marder Eve
Published: May 2019

The crustacean stomatogastric nervous system has become one of the premier preparations used for the study of the mechanisms underlying the generation of rhythmic motor patterns. The stomatogastric ganglion (STG) contains about 30 neurons, most of which are motor neurons that innervate more than 40 sets of striated muscles that move the animal’s stomach. Descending projection neurons from the two commissural ganglia (CoGs) and the single oesophageal ganglion (OG) are important for the generation of the motor patterns produced by the STG. Identified sensory neurons project either into the CoGs to activate descending modulatory neurons, or directly into the STG.
The Mauthner Cell Microcircuits: Sensory Integration, Decision-Making, and Motor Functions
Authors: Faber Donald S. , Korn Henri
Published: May 2019

The teleost and amphibian Mauthner (M) cell is the critical decision-making element in a brainstem microcircuit that decides whether unimodal or multimodal stimuli are sufficiently threatening to the animal’s survival to warrant a massive motor response. This behavior, called the startle response or C-start, was initially characterized as a reflex, when in fact its governing process involves computations that can occur over a period as short as a few milliseconds or as long as 0.5 s. Because much of what is known about this system was derived from studies in goldfish of the C-start evoked by loud, abrupt sounds and from the associated basic electrophysiology, this behavior is discussed first. Then the chapter addresses M-cell-initiated escapes triggered by more complex stimuli and the notion that the behavior can be voluntary. Finally, it describes insights from studying the M-cell system that provide a model for the construction of brainstem decision-making microcircuits.
The Lamprey Locomotor Central Pattern Generator
Authors: Grillner Sten , Jalalvand Elham , Wallén Peter
Published: May 2019

The lamprey network coordinating locomotion has been studied extensively. As in all other vertebrates investigated, the pattern generation is provided at the spinal-cord level, whereas the decision to activate the network is controlled primarily by the locomotor command centers in the brainstem (i.e., the mesencephalic locomotor region and diencephalic locomotor region), which in turn are controlled from the basal ganglia in the forebrain. The core of the segmental locomotor network is formed by pools of excitatory interneurons that can excite each other and generate burst activity . Inhibitory glycinergic or GABAergic neurons are not required in this process. Therefore, there is a core unit CPG on each side of the spinal cord that can operate without inhibitory mechanisms. The latter do, however, play a critical role for left–right coordination between the two sides. This chapter will discuss the segmental rhythm-generating circuits and the mechanism underlying intersegmental coordination.
Modularity and Modulation of Locomotor Circuits in Adult Vertebrates
Authors: Manira Abdeljabbar El
Published: May 2019

The compartmentalized organization of the nervous system entails that specific functions are localized in different brain areas and regions of the spinal cord. Dedicated microcircuits in each region/area generate relevant motor behaviors by virtue of their connectivity and dynamic computations, combined with their ability to integrate internal and external cues. The patterns of motor actions are often versatile, with continuous change in speed and coordination as circumstances demand. How this versatility is encoded within microcircuits in the brain and spinal cord is a question that has been difficult to address. Although many mechanisms can contribute, two important tenets underlying this versatility are the modularity and modulation of microcircuits.
Acute Pain Medicine Services
Authors: Warlick Alicia Lopez , Bullock W. Michael , Gulur Padma
Published: May 2019

This chapter discusses how defining the structure and procedures of an acute pain service (APS) is essential to its success. The regional anesthesiologist will lead the efforts, choosing specific peripheral nerve blocks and multimodal analgesic techniques in the preoperative block area and continuing care in the operating room and later in the postoperative area. The APS extends to the patient floors, where a pain management plan is established by the acute pain specialist and augmented by knowledgeable practitioners in this area. Measuring outcomes such as pain scores and functional status is important; such data should be collected and reported to keep the goals of the APS patient centered and to demonstrate value for the hospital. Finally, the goals of the APS should align with the clinical and financial goals of the hospital it serves.
Pain Management for Whipple Surgery
Authors: Nguyen Linh T. , Soliz Jose M.
Published: May 2019

This chapter addresses pain management in pancreatic cancer patients undergoing a Whipple procedure, in whom controlling pain is challenging in the presence of patient comorbidities such as liver cirrhosis, chronic kidney disease, and atrial fibrillation on anticoagulants. Most drugs are metabolized by the liver and excreted by the kidneys. A multimodal pain management approach can most effectively minimize the undesirable side effects of opioids. Peripheral nerve blocks and neuraxial blocks are excellent options. Traditionally, epidurals were commonly used for pain management for Whipple surgeries. However, transversus abdominis plane blocks have gained popularity partly with the increasing availability of portable ultrasounds, the lack of sympathectomy and resultant hypotension with the transversus abdominis plane (TAP) block, and the presence of contraindications to neuraxial anesthesia. The World Health Organization devised a 3-step ladder to guide physicians worldwide in the management of cancer pain, and this guide serves as an important conceptual framework for the treatment of chronic somatic, visceral, and neuropathic pain. The ladder is also useful for “step-down” analgesia in the perioperative period.
Colorectal Surgery
Authors: Persinger Aaron , Gonzales Jeffrey
Published: May 2019

Over the past 30 years, the average length of stay after colorectal surgery has decreased from 8 to 10 days in the mid-1990s to 1 to 2 days with a laparoscopic approach in the setting of an enhanced recovery program. The time it takes a patient to return to his or her baseline functional status has also been reduced. This has been achieved by comprehensively addressing the negative physiologic effects of the stress response associated with surgery. Properly timed interventions such as preoperative preparation of the patient, various regional anesthesia techniques, avoidance of medication side effects, and avoidance of postoperative complications seem to work synergistically to speed recovery. This chapter outlines preoperative, intraoperative, and postoperative considerations that may help patients make it through their perioperative journey with increased safety, comfort, and efficiency.
Polytrauma
Authors: Shields Cynthia H. , Bleckner Lisa
Published: May 2019

Pain management of the polytrauma patient requires thorough understanding of the patient’s history, complete examination, and consideration of the trajectory of care. Multimodal options for treatment include medications, regional anesthesia, and nonmedication treatments. Rapid management of pain is critical to prevent development of chronic pain and possibly for the prevention phantom limb pain. This chapter reviews the important features of the history and physical exam of a polytrauma patient. Treatment options for pain are discussed. The risks of multimodal analgesia, including oversedation and prolonged high dose opioid use are discussed. Compartment syndrome is an important concern in this population and is reviewed considering the potential for masking its detection with regional anesthesia.
Family Travel
Authors: Brunette Gary W. , Nemhauser Jeffrey B.
Published: May 2019

Pregnant Travelers

Diane F. Morof, I. Dale Carroll

Travel & Breastfeeding

Erica H. Anstey, Katherine R. Shealy

Traveling Safely with Infants & Children

Michelle S. Weinberg, Nicholas Weinberg, Susan A. Maloney

Vaccine Recommendations for Infants & Children

Michelle S. Weinberg

International Adoption

Mary Allen Staat...
Instant Neurological Diagnosis
Authors: Hawkes Christopher H. , Sethi Kapil D. , Swift Thomas R.
Published: May 2019

Experienced neurologists work fast. They ask few questions, maybe perform a brief examination, and they come up with the right answer. Sometimes they do neither and their conclusions are accurate—but how do they do it? This book holds the answers.
The book is divided into 14 chapters which, for the most part, focus on a particular neurologic condition, namely: demyelination, headache, epilepsy and sleep, myopathy and motor neuron disorders, movement disorders, stroke, peripheral neuropathy, cerebellar ataxia, and dementia. The remaining chapters are concerned with the clinician’s initial impressions (first encounters), cranial nerves, limbs and trunk, spinal lesions, and cerebrospinal fluid. At the end of each chapter is a summary of the salient points and a few key references. The final chapter relates to the fast neurological examination. Most diagnostic clues or “Handles” are illustrated by a table, figure, or video clip to reinforce a particular message, and the text is marked with Red Flags that the clinician must be alert for.
Cerebellar Ataxia
Authors: Hawkes Christopher H. , Sethi Kapil D. , Swift Thomas R.
Published: May 2019

This chapter deals with disorders of the cerebellum and its connections. These conditions may be identified by the pattern of onset—whether acute, chronic, or episodic. The chronic ataxias are inherited in various patterns: autosomal dominant, autosomal recessive, X-linked. Some episodic ataxias have variable inheritance. Other episodic ataxias without a clear genetic basis are detailed.
Insight from National Experts: From the Community-Based Organization Sector
Authors: Foreman Kim , Chappelle Sandra Byrd
Published: May 2019

Chapter 4 looks at the growing understanding of the relationship (intersectionality) between human health and other leading indicators of well-being that has come as a consequence of an increase in understanding of the social determinants of health. These indicators include full employment, educational attainment, and fair mortgage lending. It looks at examples of the work of nongovernment organizations (NGOs) together with public health officials and hospitals.
Overview—Collaboration: The Role of Multiple Sectors in Improving Health
Authors: Bradley Don W. , Castrucci Brian C.
Published: May 2019

This chapter introduces the chapters that encompass the second section of the book. It looks at the influence of American culture on the history of public health and community partnerships. There has been a dual shift throughout time in the United States: a strong work ethic and individualism and a desire of multiple stakeholders to work together to produce health outcomes to sustain the strong work ethic. This part of the book looks at some of the critical components of a successful collaboration. The aim is to identify how various community sectors can and do contribute to collaborations. It asks how these can be scaled up and sustained.
Engaging Residents for Health Transformation
Authors: Stojicic Pedja
Published: May 2019

This chapter presents a typology for engaging communities (residents) on three levels: firstly, awareness and participation; secondly, feedback and input; and, thirdly, active resident leadership. It offers lessons, tools, and practices to facilitate true engagement. It start by looking at what is actually meant by the word “engagement,” in order to unpack the actual practices associated with the word “engagement,” and learn more about the outcomes that partnerships can expect to achieve by implementing any one of those practices. Finally, it looks at how important feelings of power, trust, and belonging are to a community.
How to Draft Successful Memorandums of Understanding and Data-Sharing Agreements
Authors: Penn Matthew , Hulkower Rachel
Published: May 2019

This chapter offers tips on crafting data-sharing agreements. Improving and increasing cross-sector collaboration in public health can be facilitated through the use of a memorandum of understanding (MOU). The chapter looks at the benefits of MOUs, and also drawbacks. It provides some case studies of successful MOUs. Cross-sector collaboration is an increasingly critical component of the public health system, the chapter concludes. Community partnerships can involve complex arrangements, with reciprocal promises to exchange goods and services, and MOUs can help organizations negotiate, organize, and maintain those relationships. For partnerships that need health care or public health data to function, a data use agreements (DUA) can provide a mechanism to define the data needed and the parameters around the intended release and use of the data.
Is the Perfect the Enemy of the Good?: Using the Data You Have
Authors: Chapple-McGruder Theresa , Slaughter-Acey Jaime , Kmet Jennifer , Ruddock Tonia
Published: May 2019

This chapter offers instructions on how to find the data needed for a particular public health improvement program. The chapter starts by defining two systems of data collection: primary and secondary. However, it is important to remember that all data has limitations. There is no such thing as perfect data. The use of primary data in practice or policy decision-making is often constrained by resources and time, as collecting robust data typically takes years. Although secondary data poses limits, such that it might be data not collected specifically for a particular health question, or not being representative of the population of interest, or perhaps there is a lag in data availability. However, the chapter concludes, things can always be improved even if perfection is never reached.
The Role of Innovation in Improving Population Health
Authors: Fisher Jessica Solomon , Teter Kellie L.
Published: May 2019

Innovation can come in many forms, this chapter states: changes in current processes that make them more efficient or effective; shifts toward different processes to achieve the same goal; or larger changes that may include rethinking the task itself. While innovation can be part of the normal work flow, innovation is disruptive when it changes established roles and relationships. The chapter looks at the role of innovation in aims at improving public health. Innovation is hard to define, and means different things to different people. Innovation is occurring in population health care practice. We should embrace the characteristics of innovation, the chapter concludes.
Building an Agenda for Population Health from the Grassroots Up
Authors: Norris Tyler , Hill Ashley
Published: May 2019

This chapter looks at the path forward to building an agenda for population health improvements. It looks at the roles of the various agents such as health care providers, health care payers, health care policymakers, health care investors, academic institutions, community organizations, and the business community. No matter what the role being played within the health system, that person or body can take the leadership role in crafting and spreading the main agenda. The role of the leader is to ask the following questions: Is there an understanding of the outcomes from current efforts? Is there clarity about what is coming out of current efforts? And if current efforts aren't generating the outcomes, then what is it going to take to do so, and how is that going to be achieved?
Case Study—The Alliance for Health Equity: Hospitals, Health Departments, and Community Partners Working Together for Health Equity in Chicago and Suburban Cook County
Authors: Lynch Jess , Cunningham Megan , Morita Julie
Published: May 2019

This chapter provides case studies from Chicago and Cook County. Chicago and suburban Cook County epitomize a complex health care and public health landscape, which the chapter outlines in detail. It lists factors that converged in 2015 to provide opportunities for a collective community health project in the area. This alchemy of factors in 2015 resulted in the launch of two hospital collaboratives with similar goals. In 2017, the two collaboratives merged to form the Alliance for Health Equity. The success of this merger is a testament to the commitment of the hospital and public health leaders to a common vision of health equity and their opposition to letting competition or individual interests undermine the collective potential.
The Role of Community Development as a Partner in Health
Authors: Jutte Douglas
Published: May 2019

This chapter introduces the community development sector, an extensive network of financially skilled institutions and members that work collectively to reduce poverty in underserved and under-resourced communities by addressing social and structural determinants of health. Offering innovative and sizeable financial opportunities to invest and improve vulnerable communities, this sector shares a common mission to improve health, generates economic growth, and catalyzes and sustains multi-sector partnerships for population health improvements. The chapter adds some narrative on personal expertise as a funder at the Robert Wood Johnson Foundation and describes how they have gotten involved with Community Development Financial Institutions.
Fighting Big Soda at the Local Level
Authors: Vernick Nikki Highsmith , Schneider Glenn E.
Published: May 2019

This chapter provides an example of focused work at the local level to achieve policy goals related to food and nutrition and discusses the role of philanthropy in leading a multi-sector partnership. Public health professionals, researchers, and advocates are calling for a comprehensive national strategy to fight the ongoing epidemics in the Western world related to the over consumption of sugar. The chapter uses the case of taking on what it calls Big Soda (sugary drinks) as an example of a success story so far.
Risk and Reason in Clinical Diagnosis
Authors: Ryle Cym Anthony
Published: May 2019

This book provides, without the use of specialist language, a description of diagnostic reasoning and error and a discussion of steps that could improve diagnostic accuracy. Drawing on work in cognitive psychology, it presents the key characteristics of human reasoning. It notes that complex cognitive tasks such as medical diagnosis require a synergy of intuition and analytical thinking and introduces the concept of bias. The book considers the value of current classifications of disease, the meaning of diagnostic thresholds, and the potential for overdiagnosis. It examines the role of the patient-centred approach in this context. It develops a description of the diagnostic process, provides illustrative examples and metaphors, and refers to the dual-process model. It suggests that medical training does not consistently provide a coherent account of diagnostic thinking and the associated risks of error. It considers the role of probability in diagnostic reasoning, noting the contribution and the limitations of both informal and mathematical estimates. It refers to clear evidence that error in medical diagnosis is a prevalent and potent cause of harm and may result from systems factors or cognitive glitches such as bias and logical fallacy. It presents cases with commentaries, highlighting the cognitive processes in diagnostic successes, near misses, and disasters. It concludes with proposals for change, notably in institutional culture; in professional culture, education, and training; and in the structure of medical records. The book advocates the development and deployment of computerized diagnostic decision support. It argues that these changes could significantly enhance patient safety.
Diagnosis Terms
Authors: Ryle Cym Anthony
Published: May 2019

This chapter considers diagnosis in its sense as a term within formal classifications. It argues that classifications are indispensable and work best for conditions that can be described precisely and objectively using the biomedical model of disease. It argues that diagnostic terms may have hidden layers of meaning, reflecting individual or cultural beliefs. It suggests that these unspoken meanings influence the outcome of treatment, and that harmful misunderstandings are not unusual. It argues that classifications are less clear when disease is defined by a threshold value on a spectrum consisting of phenomena that are also experienced by people who feel well, and that this difficulty can contribute to overdiagnosis. It argues that, in these circumstances, it is of paramount importance that doctors should inform and involve patients in decisions about treatment. It recognizes the value of the patient-centred approach but argues that this does not resolve all the dilemmas.
Diagnostic Reasoning
Authors: Ryle Cym Anthony
Published: May 2019

This chapter describes the diagnostic process and provides illustrations from the author’s experience. It notes that the clinical encounter has parallels in hypothetico-deductive reasoning, sharing key elements but not the sequential structure. It refers to the consensus that the thinking of experienced clinicians seldom follows a simple sequence and is driven by intuition, augmented by analytical approaches. Suggested is that success depends on their synergistic function. It argues that the greatest challenge in diagnostic reasoning is the need to integrate imperfect information to synthesize a coherent conclusion. It notes that the cognitive mechanisms are complex, obscure, and prone to error. It describes common biases and argues that both cognitive and affective bias are potent sources of error. The chapter proposes that the model of diagnostic reasoning implicit in traditional medical education should be replaced by a more explicit and complex description incorporating these insights.
Dyslipidaemia
Authors: Drexel Heinz
Published: May 2019

Lipid metabolism has gained cardiological interest only after statins were demonstrated to reduce cardiovascular disease in secondary and primary prevention. Therefore, this chapter first introduces the physiological and atherogenic properties of lipoproteins, before focusing on interventions. Both the efficacy and safety of statins have been proven in numerous randomized clinical trials. Because there is a considerable residual risk in statin-treated patients, additional approaches have been investigated. The focus is now on further reductions in low-density lipoprotein (LDL) cholesterol levels. First, high-intensity statin regimens were shown to reduce residual risk. Subsequently, ezetimibe was demonstrated, for the first time, to have a beneficial effect as a non-statin lipid intervention. More recently, inhibitors of the enzyme PCSK9 have demonstrated a very high efficacy in reducing LDL cholesterol levels. Although the causality of LDL for atherosclerotic cardiovascular disease has been proven in epidemiological studies, including Mendelian randomization studies, as well as interventional trials, adherence to statins and other therapies is far from optimal. In contrast, interventions to increase high-density lipoprotein (HDL) cholesterol levels could not proven to have further benefits when combined with statins.
Metabolic syndrome and diabetes
Authors: Saely Christoph H.
Published: May 2019

The metabolic syndrome (MetS) and even more so diabetes confer a significantly increased risk of cardiovascular disease. A multifactorial approach is required to improve the prognosis of patients with the MetS or diabetes. Glucose control is essential to reduce microvascular diabetes complications and, over long periods of time, may also lower the risk of cardiovascular events in patients with diabetes. As in other patient populations, lowering low-density lipoprotein (LDL) cholesterol and treating arterial hypertension are paramount interventions to reduce cardiovascular event risk in patients with the MetS and diabetes. Most patients with diabetes must be considered at a very high risk of cardiovascular events, which qualifies them for low LDL cholesterol targets. An-tiplatelet therapy is recommended for patients with the MetS or diabetes who already have established cardiovascular disease. Because the MetS or diabetes confers an extremely high risk of cardiovascular events once cardiovascular disease is established, it is extremely important to intervene early to prevent these patients from developing cardiovascular disease.
Coronary artery spasm and microvascular angina
Authors: Ong Peter , Sechtem Udo
Published: May 2019

Ischaemic heart disease comprises a variety of coronary abnormalities, ranging from obstructive atherosclerotic stenoses to functional coronary vasomotor disorders. The latter comprise coronary spasm, as well as coronary microvascular dysfunction. Importantly, structural and functional abnormalities can coexist in a given patient, making it sometimes difficult to determine the underlying cause of angina. Thus, diagnostic algorithms should not only consider the evaluation of atherosclerotic epicardial disease, but also look for the presence of functional coronary disorders. This holds especially true for patients in whom obstructive coronary disease has been excluded, as many of these patients are labelled as having ‘non-cardiac chest pain’. Such an approach may enable the treating physician to adjust the pharmacological therapy more appropriately, in order to improve symptoms and prognosis. Often drug classes such as calcium channel blockers and nitrates are beneficial in these patients. This chapter gives an overview on the current pharmacological management of patients with coronary artery spasm and those suffering from microvascular angina.
Heart transplantation
Authors: Gustafsson Finn , Rossing Kasper
Published: May 2019

Heart transplantation remains the treatment of choice for end-stage heart failure refractory to conventional treatment. Long-term outcome is excellent, and median survival currently exceeds 13 years. The main causes of death late after transplantation are cardiac allograft vasculopathy and cancer. Medical therapy after transplantation is complex, including immunosuppressive therapy to reduce the risk of graft rejection and prophylaxis against viral and protozoal infections, as well as adjunctive therapy to treat common comorbidities, for instance hypertension. Pharmacological therapy of comorbid conditions requires specific consideration to clinically important interactions with immunosuppressive drugs.
Supraventricular (narrow complex) tachycardias
Authors: Martí-Almor Julio
Published: May 2019

Supraventricular tachycardia (SVT) includes all tachycardia rhythms (more than 100 bpm), of which the mechanism involves the His Bundle or tissues above it. Usually, these tachyarrhythmias present a narrow QRS complex (except in the presence of a bundle branch block or a manifest accessory pathway which conducts anterogradely to cause a ventricular pre-excitation pattern on the electrocardiogram). This chapter only focuses on narrow QRS complex SVT involving the atrial tissue, the atrioventricular node, and accessory pathways. Atrial fibrillation and atrial flutter are excluded because they are specifically covered in other chapters. The role of antiarrhythmic drugs in SVTs is mainly restricted to acute situations because ablative therapy has surrogate pharmacotherapy and ablation is considered the best long-term treatment for most cases. Nevertheless, it is very important to know how to deal with antiarrhythmic drugs in emergency situations.
Bradyarrhythmias
Authors: Burri Haran
Published: May 2019

This chapter overviews the types of bradycardia and their acute management, including the use of rate-accelerating drugs, and overviews the indications for pacemaker therapy. Focus is on pharmacotherapy with atropine, adrenaline, isoprenaline, isoproterenol, dobutamine, dopamine, theophylline, and aminophylline.
Valvular heart disease
Authors: Mantovani Francesca
Published: May 2019

Valvular heart disease is common, and any of the four valves of the heart can be affected, although left-sided valvular disease is far commoner than right-sided disease. Treatment depends on the valvular disease type and severity but, when severe and symptomatic, usually involves mechanical intervention. Asymptomatic patients without objective parameters suggesting high morbid or lethal risk are closely observed clinically, until surgical indications develop. Although often prescribed, no rigorous evidence supports pharmacological therapy in most chronic valve diseases, although drugs may be useful in acute valvular diseases or as a bridge to surgery in severely decompensated patients. Moreover, given the rising proportion of frail older people with symptomatic degenerative valve disease, in whom the risks of mechanical intervention are prohibitive, medical treatment could be the only option.
Major drug interactions
Authors: Poulsen Maja Hellfritzsch , Krogh Marlene Lunddal
Published: May 2019

Drug interactions are commonly present in our daily clinical work and have the ability to either enhance or reduce the effects of a drug, but also, just as importantly, decrease or increase the risk of side effects, thereby increasing the risk of toxicity. This chapter will focus on the clinically important drug–drug interactions with some of the most often used cardiovascular drugs and especially where there is a risk of causing harm to patients due to serious side effects. Both pharmacokinetic and pharmacodynamic interactions will be discussed, with focus on the most vulnerable patients. In some cases, drug combinations are contraindicated, whereas in other cases, the combinations can be used with, for example, close monitoring or dose reductions, but most importantly, the risk of interactions should be considered in order to take appropriate precautions upfront.
Non-cardiac drugs affecting the heart—from A to Z
Authors: Delpón Eva , Tamargo Juan
Published: May 2019

Non-cardiac drugs affecting the heart.
Evolution and cancer
Authors: Donnem Tom , Micklem Kingsley , Pezzella Francesco
Published: May 2019

Evolution is the process by which living organisms change through time, and natural selection is the process which leads some organisms to thrive and others to die out. Evolutionary medicine tries to explain why traits leading to susceptibility to disease get maintained or even positively selected. Cancer, being a genetic disease, can be analysed as an example of evolution by natural selection. The observation that humans in developed societies have much higher rates of cancer can be analysed and explained by an evolutionary approach. At a cellular level, tumours are made up by a population of cells continuously growing and mutating while interacting with the microenvironment of the body. Thus, the mechanism of changes in individual tumours is the process of natural selection. Evolutionary biology is now increasingly used to better understand tumour growth and therefore to improve treatments.
Epigenetics
Authors: Hookway Edward , Athanasou Nicholas , Oppermann Udo
Published: May 2019

Epigenetics is a term that refers to a collection of diverse mechanisms that are important in both the control of gene expression and the transmission of this information during cell division. Epigenetic processes are deranged in many cancers, leading to a combination of inappropriate silencing of tumour suppressor genes and overexpression of oncogenes. In this chapter, the molecular mechanisms that underpin the major epigenetic processes of DNA methylation, histone modification, and non-coding RNAs will be described in both their normal physiological roles and in the context of cancer. The challenge of understanding the complexity of the interactions between different epigenetic mechanisms and the limitations of our current knowledge will be highlighted. Therapeutic approaches towards targeting deranged epigenetic processes will also be described, such as the use of small molecule inhibitors of histone deacetylases.
Chemical carcinogens
Authors: Phillips David H.
Published: May 2019

Large geographical and temporal differences in cancer incidence indicate that the causes of the majority of cases are a consequence of environmental and lifestyle factors. While many of these remain unknown, around half have known causes, and these include chemicals in air, water, and food, as well as products of industrial processes and of combustion. The major classes of chemical carcinogens and how they were discovered are described. A property shared by many of them is that they, or one or more of their metabolites, are electrophiles that can damage DNA in mammalian cells, leading to cellular responses including DNA repair, cytotoxicity, apoptosis, mutagenesis, and malignant transformation. Methods for predicting the carcinogenicity of new chemicals are part of the regulatory processes for safety assessment, and sensitive methods for monitoring human exposure to carcinogens provide insight into the aetiology of cancer. The mutational signatures that genotoxic carcinogens leave in the tumours they induce provide evidence of the chemicals that have caused them, and the approach has promise for shedding light on the many as-yet-unidentified cases of cancer worldwide.
Cell cycle control
Authors: Carr Simon , La Thangue Nicholas
Published: May 2019

The cell cycle constitutes a series of events that lead to the duplication of the cell’s DNA and the generation of two new daughter cells. During the initial stages, the cell grows and expresses numerous genes in preparation for DNA replication, while during the final stages, this newly synthesized DNA is segregated to opposite poles of the cell and the cytoplasm is divided to generate two new daughters. To ensure proper progression from one cell cycle stage to another, the cell employs a number of control mechanisms (known as checkpoints), which constitute a complex set of signalling pathways that respond to both external and internal cues. When these checkpoints function incorrectly, as may occur in response to genetic mutation, the cell cycle control system begins to break down, and this can result in the onset of many human diseases including cancer. Our understanding of the molecular details of cell cycle control is therefore intimately linked with our ability to develop novel cancer therapy and has been a burgeoning area of scientific research for several decades. The molecular details of how the cellular checkpoints function will be summarized within this chapter, with specific examples given of genetic aberrations that compromise this control system, and how such mutations contribute to the onset of tumorigenesis.
Cancer and cell death
Authors: Bullenkamp Jessica , Tavassoli Mahvash
Published: May 2019

Programmed cell death is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. Regulated programmed cell death is one of the mechanisms by which multicellular organisms limit the growth and replication of cells. Cell death is essential to control cell growth and tissue homeostasis; it occurs in normal tissues to allow the removal of damaged cells or to maintain a constant number of cells in regenerating tissues and plays an important part in embryogenesis. In an average human adult 50–70 billion cells undergo programmed cell death every day. The abundance of literature suggests that defects in programmed cell death play a crucial role in carcinogenesis. The genetic alterations in the cancer cell not only lead to increased cellular proliferation, as discussed in other chapters of this book, but also lead to loss of programmed cell death, thus increasing tumour growth. Despite being part of the problem, cell death plays an important role in the treatment of cancer as it is an important target of many treatment strategies. Unquestionably, apoptosis is the best-characterized and the most evolutionary conserved form of programmed cell death. Recently, many studies have demonstrated the existence of several other forms of programmed cell death including autophagy, necroptosis, and pyroptosis. In this chapter we discuss several regulated forms of cell death; we outline what we know about their mechanisms and how we can exploit this knowledge to reactivate programmed cell death in tumour cells for the treatment of cancer.
Cancer metabolism
Authors: Schulze Almut , Bensaad Karim , Harris Adrian L.
Published: May 2019

Abnormalities in cancer metabolism have been noted since Warburg first described the phenomenon of glycolysis in normoxic conditions. This chapter reviews the major pathways in metabolism known to be modified in cancer, including glycolysis and the Krebs cycle, the pentose shunt, and new data implicating the role of different metabolic adaptations, including oncometabolism. It highlights the genetic changes that effect metabolism including many of the commonly occurring oncogenes but also rare mutations that specifically target metabolism. Nutrient and oxygen limitation and proliferation create the microenvironmental selective stress for modifications in hypoxic metabolism, but also affect other cell types such as endothelial cells and macrophages. This range of changes provides many new therapeutic approaches. It also describes the potential value of targeting these adaptations and approaches to monitoring in vivo effects in patients to monitor therapeutic activity.
Benign tumours: The forgotten neoplasms
Authors: Pezzella Francesco , Harris Adrian L. , Tavassoli Mahvash
Published: May 2019

Benign tumours are exceedingly common neoplastic growth which, similar to malignant tumours, recognize genetic basis. However, benign tumours differ in one essential characteristic: by definition, these neoplasms do not produce metastases. Only some types are at risk of progression into a malignant lesion. Complete surgical removal is always curative. Because of their non-aggressive ‘benign’ nature and, in many cases, easy, straightforward possibility of surgical treatment, the biology of these tumours has not received much attention as compared to that of the malignant neoplasms. However, several studies have recently started to unveil the involvement of mechanisms overlapping with those of the malignant lesions, raising the issue that, by ignoring the biology of benign tumours, we are perhaps missing information vital for understanding malignancies. Only a few types have been subjects of studies comparable to that we can found in malignancy and therefore their biology is still largely unknown.
The Medical Model in Mental Health
Authors: Huda Ahmed Samei
Published: May 2019

The medical model is a biopsychosocial model assessing a patient’s problems and matching them to the diagnostic construct using pattern recognition of clinical features. Diagnostic constructs allow for researching, communicating, teaching, and learning useful clinical information to influence clinical decision-making. They also have social and administrative functions such as access to benefits. They may also help explain why problems occur. Diagnostic constructs are used to describe diseases/syndromes and also other types of conditions such as spectrums of conditions. Treatments in medicine and psychiatry have several treatment objectives including cure or reducing distress and a variety of mechanisms of action apart from reversing disease/cure. Causation of conditions in medicine and psychiatry are often complex. The medical model allows doctors to assess and offer effective treatments to large numbers of patients and provide emergency cover. Diagnostic constructs in psychiatry and general medicine overlap for attributes such as clinical utility (e.g. predicting likely outcomes) and validity (e.g. lack of boundaries between different diagnostic constructs) and importance of social factors. There is an overlap in effectiveness between psychiatric and general medicine treatments and many general medicine medications do not reverse disease processes. Different mental health classifications have particular strengths and weaknesses for clinical, research, and social functions. Mental health research into understanding causes and mechanisms may need other classifications than diagnosis. As doctors in all specialties encounter mental health problems, there will always be psychiatric diagnostic constructs compatible with their training. Mental health research and service provision will always need to address psychosocial issues.
The role of diagnosis in medical practice and society
Authors: Huda Ahmed Samei
Published: May 2019

Organization of knowledge is needed to help doctors learn and recall information in their clinical practice. Diagnostic constructs help, providing prototypes against which doctors can diagnose patient conditions. They then seek to confirm or disprove this diagnosis by searching for relevant information. Attached to these diagnostic constructs are information such as causes, prognosis, and treatment. Diagnostic constructs are provisional and should be changed if information suggests they are incorrect. They also aid communication between professionals for teaching and research, and have important social functions such as providing access to healthcare, determining eligibility for welfare, offering administrative and payment functions, and collecting health statistics. Some social effects of diagnostic constructs can be harmful, such as stigma. Diagnostic constructs are included in broad diagnostic formulations including relevant clinical information.
Criticism of psychiatric diagnosis
Authors: Huda Ahmed Samei
Published: May 2019

Criticisms of psychiatric diagnostic constructs from a clinical/scientific view have been made on several points: reliability, such as how often two clinicians agree on the same diagnosis; validity, such as clear separation between diagnostic constructs or presence of objective validators; utility, such as predicting outcomes and treatment responses; implying an inaccurate conception of mental health problems as diseases that also minimizes the influence of social causative factors, high rates of co-occurrence, and association with negative consequences such as stigma. Many psychiatric diagnostic constructs lack validity but often have clinical utility. This clinical utility depends on how the clinician works therefore psychiatric diagnostic constructs are well suited to the medical model but may have little utility for other mental health professionals who work differently or for researchers testing hypotheses. Diagnostic constructs have utility for administrative purposes. The criticisms can be used to generate a set of questions to evaluate psychiatric diagnostic constructs. Psychiatric diagnostic constructs are best compared with general medical diagnostic constructs because they are used for similar purposes in clinical decision-making. A comparison will be made to see if there is no overlap, some overlap, or near total overlap between general medical and psychiatric diagnostic constructs.
Reliability of diagnosis
Authors: Huda Ahmed Samei
Published: May 2019

Reliability of a diagnosis can be measured as either agreement with a reference criterion or agreement between clinicians as to a diagnosis. Most psychiatric and some general medical diagnostic constructs are identified on the basis of a clinical picture, not using a reference criterion such as laboratory tests. Most psychiatric diagnostic constructs have moderate to substantial reliability in research studies. They are likely to be less reliable in clinical practice. Measures such as standardizing interviews can improve reliability. General medical diagnostic constructs have similar reliability to psychiatric diagnostic constructs in research studies and are also likely to be less reliable in clinical practice. Even with laboratory tests, some medical conditions are hard to distinguish due to similarities in their clinical pictures. For alternative mental health classifications, psychological formulation—except psychodynamic formulation—is less reliable than psychiatric diagnosis. Symptom-based classification has at least equal reliability to psychiatric diagnosis. Dimension-based classification has equivalent reliability to psychiatric diagnosis. These may be combined with diagnosis but may have less usefulness on their own for other functions, e.g. administrative.
Social factors and health
Authors: Huda Ahmed Samei
Published: May 2019

There is increased risk caused by social difficulties and/or childhood trauma for developing both general medical and mental health conditions, with overlap in similarity of magnitude of some increased risks, although intermediary mechanisms may differ. Social factors are the most important determinants of health status. Reducing social adversity and childhood trauma would improve the physical and mental health of the population. Life events and stresses/hassles are a more specific risk factor for mental health problems. Social factors are often inadequate to explain the nature and severity of people’s mental health problems without taking into account psychobiological factors. Given the greater effect of culture on how mental health conditions are expressed, there is some overlap between psychiatric and general medical diagnostic constructs rather than near total overlap. Mental health conditions do seem associated with greater stigma (some of this seems related to the categorical nature of diagnostic constructs) and also with greater use of coercion than for general medical conditions, but this also occurs for general medical conditions hence the conclusion of some overlap.