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Interest in processes at the nexus of host–microbe–metal interactions has risen as a result of advancements in the study of metallomics, proteomics, and genomics. These emerging fields have given rise to new developments in powerful analytical methods and technology for studying the identity, distribution, quantity, trafficking, fate, and effects of trace metals in biological systems. Applications of these advanced techniques to the study of metabolic cycles are yielding results and have placed scientists at the threshold of major paradigm shifts in our understanding of the relationships between homeostatic mechanisms of trace metals and pathogenesis of infectious diseases. Fields present at this Forum included chemistry, biology/biochemistry, toxicology, nutrition, immunology, microbiology, epidemiology, environmental and occupational health, as well as environmental and veterinary medicine. Participants were tasked with using their knowledge to discuss how the metabolic cycles of trace metals relate to the pathogenesis of disease during infection. The stimulating dialog that ensued covered a wide range of views, insights, and perspectives on current knowledge and raised important open questions that should be addressed by future research initiatives.

Individuals with autism demonstrate marked impairments in the perception, processing, and interpretation of social information. Recent findings suggest that abnormal social orienting may serve as a persistent and developmentally critical mechanism underlying deficits in this domain, and may help differentiate autism from other neurodevelopmental disorders sharing similar social cognitive impairments. This chapter uses social orienting as an example of the significant benefit that can be gained by integrating the fields of cognitive neuroscience and developmental psychopathology through the identification of neuropsychological mechanisms contributing to the development of abnormal brain–behavior relationships. Social orienting may represent a potentially fruitful mechanism for disentangling the pathogenesis of social deficits in autism.

Multiple sclerosis (MS) is considered an autoimmune chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal damage. The view of MS as a “two-stage disease”, with a predominant inflammatory demyelination in the early phase (relapsing-remitting MS form) and a subsequent secondary neurodegeneration in the early phase (secondary or primary progressive MS) of the disease, is now challenged by the demonstration that axonal destruction may occur independently of inflammation and may also produce it. Therefore, as CNS inflammation and degeneration can coexist throughout the course of the disease, MS may be a “simultaneous two-component disease”, in which the combination of neuroinflammation and neurodegeneration promotes irreversible disability. This chapter discusses factors that contribute to the pathogenesis of MS, immune surveillance in the CNS, regulation of immune responses in the inflamed CNS, initiation of T helper 1 (Th1)-mediated immune reactions in the inflamed CNS, amplification of Th1-mediated immune responses in inflamed CNS and tissue damage, and development of autoimmunity in MS.

This chapter looks at a case study to show the desired skills, attitudes, and knowledge needed to diagnose and manage delirium in palliative care patients. It considers several issues such as: How common is cognitive impairment in patients with advanced cancer? What are the core criteria for a diagnosis of delirium? What are the additional associated clinical features? How might the history and physical assessment help to clarify the diagnosis? What are the major aetiological factors associated with delirium in the palliative care setting? What is the pathogenesis of delirium?

This chapter examines the pathogenesis of venous thromboembolism (VTE) in patients with cancer. It explains that patients with cancer are more likely to develop VTE than those without. This is because the coagulation cascade is activated by factors related both directly and indirectly to the tumour, and all parts of Virchow's triad may be involved with the development of thrombosis. Despite the progress in thrombosis research, many questions remain unanswered including the role of primary thromboprophylaxis and the possibility of adjuvant anticoagulation as an anticancer therapy.

It has been estimated that about 10% of hospitalized patients require urinary catheterization. Urinary tract infections (UTIs) following catheterization are the most common infections, accounting for up to 40% of all health care associated infections. This chapter discusses risk factors, pathogenesis, microbiology, diagnosis, prevention strategies, and management of patients with bacteriuria and infections.

Health care-associated pneumonia in hospitalized patients has a mortality rate of up to 40%. Although pneumonia may occur in patients throughout the hospital stay, the patients at greatest risk are those who are intubated to enable them to be managed on mechanical ventilatory support. This chapter discusses the definition and microbiology of hospital-acquired pneumonia and ventilator-associated pneumonia (VAP), pathogenesis of VAP, and prevention strategies.

This chapter concentrates on the pathophysiology of cardiac cachexia. It also discusses the possible clinical implications, and outlines the potential future development of therapeutic strategies. In particular, it explores the epidemiology and aetiology of cardiac cachexia. It then evaluates the alterations of body composition and the pathogenesis of cardiac cachexia. The therapeutic options include pharmacological treatment, nutritional support, and physical training. With improved knowledge of the underlying pathophysiology, a number of emerging treatment strategies for prevention and treatment are being developed and tested. Although no specific treatment is currently available, several approaches with the use of neurohormonal drugs, nutritional support, ghrelin, and physical training appear to show potential benefits and the results of ongoing clinical trials in cardiac cachexia are awaited.

Asbestosis can be considered either a clinical disease, which is manifest functionally, and readily demonstrable by radiological means, or a pathological entity of variable degrees of severity, but often as scattered localized lesions in the lungs in the absence of clinically evident respiratory insufficiency. This chapter considers the pathogenesis and pathological features of asbestosis from the perspective of its epidemiology.

Cancer of the pancreas remains a serious medical and public health problem because of difficulties in early diagnosis, aggressive behavior, resistance to therapy, and limited opportunities for prevention. This chapter reviews the epidemiology of pancreatic cancer. Topics covered include classification, diagnosis, incidence, mortality, survival, time trends in the United States, risk factors, host factors, molecular pathogenesis, and prevention.

The hereditary nature of migraine has been reported consistently since it was first noted by S. A. Tissot in the 18th century. Indeed, the association between migraine and family history was believed to be so strong that it was included as a criterion for diagnosing migraine in the definition adopted by the Ad Hoc Committee on the classification of headache in 1962. The most recent catalogue of Mendelian diseases in humans lists migraine as an autosomal dominant condition. Nevertheless, both the role of genetic factors in the pathogenesis of migraine and its mode of inheritance continue to be elusive.

There have been many attempts to explain the pathophysiological mechanism of migraine — for example, the platelet theory, the biogenic amine theory, or the vascular, vaso-neurogenic, and neural theories. There is still general agreement that the migraine aura is associated with a regional vasoconstriction, whilst the headache phase is accompanied by a localized vasodilatation of the cranial arteries. It is also a generally held concept that 5-hydroxytryptamine (5-HT, serotonin) is somehow involved in the pathogenesis of the disease. This chapter hypothesizes that the vasodilator phase of migraine is mediated by two powerful vasorelaxants, which are generated by the endothelium, namely prostacyclin and the ‘endothelium-derived relaxing factor’ which has been identified as nitric oxide (NO).

Progress in the understanding of migraine pathogenesis has been hampered by the unavailability of animal models for this disorder. Thus, there has been limited study of the human condition itself. Until recently, direct examination of brain function could not be performed without hazard to the patient. Now, with techniques such as positron emission tomography, nuclear magnetic resonance spectroscopy, 133Xe-inhalation cerebral blood flow (CBF), and magnetoencephalography we can derive insights into central mechanisms of the attack. This chapter reviews the evidence obtained by these non-invasive techniques in the context of a conceptual mechanism for migraine — that is, that the attack is due to an abnormality of the normally finely tuned interaction between neuronal and vascular elements of the central nervous system (CNS).

Although the CNS has conventionally been viewed as an immunologically privileged site, the importance of immunological responses in the pathogenesis of CNS disease has become increasingly apparent over the last few decades. Indeed, the concept of CNS isolation from the immune system is hard to reconcile with the favourable outcome of encephalitides commonly complicating some exanthemata, such as mumps, and with the brisk cerebrospinal fluid pleocytosis, which almost invariably accompanies brain infection; neither observation suggests that CNS invasion by infective agents proceeds unhindered by immune response. However, whilst absolute immune privilege can no longer be sustained, is has become clear that there are fundamental differences between the mechanisms of immunity in the CNS and those elsewhere in the body. In order to understand the part inflammation plays in both pathogenesis and repair, it is necessary to consider briefly both the principles of the systemic immune response and the blood–brain barrier, which protects nervous tissues from the systemic circulation.

Regardless of the many considerations, GR43175 has been shown to be effective when administered subcutaneously and orally as well as when administered intravenously in the treatment of acute migraine. It is now in phase III clinical trials and promises to provide a major breakthrough in migraine therapy. Importantly, further studies on its clinical mechanism of action are in progress and they will, it is hoped, be invaluable in elucidating the pathogenesis of migraine and vascular headache.

This chapter presents a personal view on the role of platelets in migraine. The chapter states a belief that much of the pathogenesis of each feature of migraine must relate to feedback loops. There must be two of these to account for the fact that the side affected by aura symptoms is not always the side affected by the headache. Each feedback loop must be able to enhance responses on one side at the expense of the other, and a loop eliminates the need to advance a single cause of migraine.

This chapter discusses pruritus, which is a symptom of chronic cholestatic liver disease. Cholestasis is defined as a syndrome that arises as a consequence of impaired bile secretion and/or flow, which leads to the regurgitation of components of bile into plasma. A pathogenesis of pruritus of cholestasis is unknown. The chapter introduces the concept of pruritus of central origin, and then discusses the opioid neurotransmitter system. The next sections focus on the opioid system and the opioid antagonists.

This chapter discusses uraemic pruritus, which can be either generalized or localized. It is sometimes referred to as dialysis pruritus. This symptom occurs in 15% of patients with chronic renal insufficiency, and its pathogenesis shows mast cells, dry skin, and skin innervation, among others. The chapter concludes with a list of the possible methods that can be used to treat uraemic pruritus.