Multimodal technology is poised to revolutionize clinical practice by integrating artificial intelligence with traditional diagnostic modalities. This evolution traces its roots from Hippocrates' humoral theory to the use of sophisticated AI-driven platforms that synthesize data across multiple sensory channels. The interplay between historical medical practices and modern technology challenges conventional patient-clinician interactions and redefines diagnostic accuracy. Highlighting applications from neurology to radiology, the potential of multimodal technology emerges, suggesting a future where AI not only supports but enhances human sensory inputs in medical diagnostics. This shift invites the medical community to navigate the ethical, practical, and technological changes reshaping the landscape of clinical medicine.

Hormones play a crucial role in maintaining the normal human physiology. By acting as chemical messengers that facilitate the communication between different organs, tissues and cells of the body hormones assist in responding appropriately to external and internal stimuli that trigger growth, development and metabolic activities of the body. Any abnormalities in the hormonal composition and balance can lead to devastating health consequences. Hormones have been important therapeutic agents since the early 20th century, when it was realized that their exogenous supply could serve as a functional substitution for those hormones which are not produced enough or are completely lacking, endogenously. Insulin, the pivotal anabolic hormone in the body, was used for the treatment of diabetes mellitus, a metabolic disorder due to the absence or intolerance towards insulin, since 1921 and is the trailblazer in hormone therapeutics. At present the largest market share for therapeutic hormones is held by insulin. Many other hormones were introduced into clinical practice following the success with insulin. However, for the six decades following the introduction the first therapeutic hormone, there was no reliable method for producing human hormones. The most common source for hormones were animals, although semisynthetic and synthetic hormones were also developed. However, none of these were optimal because of their allergenicity, immunogenicity, lack of consistency in purity and most importantly, scalability. The advent of recombinant DNA technology was a game changer for hormone therapeutics. This revolutionary molecular biology tool made it possible to synthesize human hormones in microbial cell factories. The approach allowed for the synthesis of highly pure hormones which were structurally and biochemically identical to the human hormones. Further, the fermentation techniques utilized to produce recombinant hormones were highly scalable. Moreover, by employing tools such as site directed mutagenesis along with recombinant DNA technology, it became possible to amend the molecular structure of the hormones to achieve better efficacy and mimic the exact physiology of the endogenous hormone. The first recombinant hormone to be deployed in clinical practice was insulin. It was called biosynthetic human insulin to reflect the biological route of production. Subsequently, the biochemistry of recombinant insulin was modified using the possibilities of recombinant DNA technology and genetic engineering to produce analogues that better mimic physiological insulin. These analogues were tailored to exhibit pharmacokinetic and pharmacodynamic properties of the prandial and basal human insulins to achieve better glycemic control. The present chapter explores the principles of genetic engineering applied to therapeutic hormones by reviewing the evolution of therapeutic insulin and its analogues. It also focuses on how recombinant analogues account for the better management of diabetes mellitus.

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel beta coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) crippled the whole world and has resulted in large number of morbidity and mortality. The origin of the SARS-CoV-2 is still disputed. The risk of infection with SARS-CoV-2 is dependent on several risk factors as observed in many studies. The severity of the disease depends on many factors including the viral strain, host immunogenetics, environmental factors, host genetics, host nutritional status and presence of comorbidities like hypertension, diabetes, Chronic Obstructive Pulmonary Disease, cardiovascular disease, renal impairment. Diabetes is a metabolic disorder mainly characterized by hyperglycemia. Diabetic individuals are intrinsically prone to infections. SARS-CoV-2 infection in patients with diabetes result in β-cell damage and cytokine storm. Damage to the cells impairs the equilibrium of glucose, leading to hyperglycemia. The ensuing cytokine storm causes insulin resistance, especially in the muscles and liver, which also causes a hyperglycemic state. All of these increase the severity of COVID-19. Genetics also play pivotal role in disease pathogenesis. This review article focuses from the probable sources of coronaviruses and SARS-CoV-2 to its impacts on individuals with diabetes and host genetics in pre- and post-pandemic era.

Diabetic neuropathy is the most common microvascular complication of diabetes mellitus and a major risk factor for diabetes-related lower-extremity complications. Diffuse neuropathy is the most frequently encountered pattern of neurological dysfunction and presents clinically as distal symmetrical sensorimotor polyneuropathy. Due to the increasing public health significance of diabetes mellitus and its complications, screening for diabetic peripheral neuropathy is essential. Consequently, a review of the principles that guide screening practices, especially in resource-limited clinical settings, is urgently needed.

Numerous evidence-based assessments are used to detect diabetic peripheral neuropathy. In accordance with current guideline recommendations from the American Diabetes Association, International Diabetes Federation, International Working Group on the Diabetic Foot, and National Institute for Health and Care Excellence, a screening algorithm for diabetic peripheral neuropathy based on multiphasic clinical assessment, stratification according to risk of developing diabetic foot syndrome, individualized treatment, and scheduled follow-up is suggested for use in resource-limited settings.

Screening for diabetic peripheral neuropathy in resource-limited settings requires a practical and comprehensive approach in order to promptly identify affected individuals. The principles of screening for diabetic peripheral neuropathy are: multiphasic approach, risk stratification, individualized treatment, and scheduled follow-up. Regular screening for diabetes-related foot disease using simple clinical assessments may improve patient outcomes.

Complex diseases often present as a diagnosis riddle, further complicated by the combination of multiple phenotypes and diseases as features of other diseases. With the aim of enhancing the determination of key etiological factors, we developed and tested a complex disease model that encompasses diverse factors that in combination result in complex diseases. This model was developed to address the challenges of classifying complex diseases given the evolving nature of understanding of disease and interaction and contributions of genetic, environmental, and social factors.

Here we present a new approach for modeling complex diseases that integrates the multiple contributing genetic, epigenetic, environmental, host and social pathogenic effects causing disease. The model was developed to provide a guide for capturing diverse mechanisms of complex diseases. Assessment of disease drivers for asthma, diabetes and fetal alcohol syndrome tested the model.

We provide a detailed rationale for a model representing the classification of complex disease using three test conditions of asthma, diabetes and fetal alcohol syndrome. Model assessment resulted in the reassessment of the three complex disease classifications and identified driving factors, thus improving the model. The model is robust and flexible to capture new information as the understanding of complex disease improves.

The Human Disease Ontology's Complex Disease model offers a mechanism for defining more accurate disease classification as a tool for more precise clinical diagnosis. This broader representation of complex disease, therefore, has implications for clinicians and researchers who are tasked with creating evidence-based and consensus-based recommendations and for public health tracking of complex disease. The new model facilitates the comparison of etiological factors between complex, common and rare diseases and is available at the Human Disease Ontology website.

In this paper, we provide an overview of the evolution of the definition of hyperglycemia during the past century and the alterations in glucose dynamics that cause fasting and postprandial hyperglycemia. We discuss how extensive mechanistic, physiological research into the factors and pathways that regulate the appearance of glucose in the circulation and its uptake and metabolism by tissues and organs has contributed knowledge that has advanced our understanding of different types of hyperglycemia, namely prediabetes and diabetes and their subtypes (impaired fasting plasma glucose, impaired glucose tolerance, combined impaired fasting plasma glucose, impaired glucose tolerance, type 1 diabetes, type 2 diabetes, gestational diabetes mellitus), their relationships with medical complications, and how to prevent and treat hyperglycemia.

Over the last few decades, several definitions of gestational diabetes mellitus (GDM) have been described. There is currently not enough research to show which way is the best to diagnose GDM. Opinions differ in terms of the optimal screening and diagnostic measures, in part due to the differences in the population risks, the cost-effectiveness considerations, and the lack of an evidence base to support large national screening programs. The basic method for identifying the disease is the measurement of glucose plasma levels which may be determined when fasting, two hours after a meal, or simply at any random time. The currently increasing incidence of diabetes in the whole population, the altering demographics and the presence of lifestyle changes still require better methods of screening for hyperglycemia, especially during pregnancy. The main aim of this review is to focus on the prevalence and modifications to the screening criteria for GDM across all continents in the 21st century. We would like to show the differences in the above issues and correlate them with the geographical situation. Looking at the history of diabetes, we are sure that more than one evolution in GDM diagnosis will occur, due to the development of medicine, appearance of modern technologies, and the dynamic continuation of research.

Hyperglycemia in diabetic patients is associated with abnormally-elevated cellular glucose levels. It is hypothesized that increased cellular glucose will lead to increased formation of endogenous methanol and/or formaldehyde, both of which are then metabolically converted to formic acid. These one-carbon metabolites are known to be present naturally in humans, and their levels are increased under diabetic conditions. Mechanistically, while formaldehyde is a cross-linking agent capable of causing extensive cytotoxicity, formic acid is an inhibitor of mitochondrial cytochrome oxidase, capable of inducing histotoxic hypoxia, ATP deficiency and cytotoxicity. Chronic increase in the production and accumulation of these toxic one-carbon metabolites in diabetic patients can drive the pathogenesis of ocular as well as other diabetic complications. This hypothesis is supported by a large body of experimental and clinical observations scattered in the literature. For instance, methanol is known to have organ- and species-selective toxicities, including the characteristic ocular lesions commonly seen in humans and non-human primates, but not in rodents. Similarly, some of the diabetic complications (such as ocular lesions) also have a characteristic species-selective pattern, closely resembling methanol intoxication. Moreover, while alcohol consumption or combined use of folic acid plus vitamin B is beneficial for mitigating acute methanol toxicity in humans, their use also improves the outcomes of diabetic complications. In addition, there is also a large body of evidence from biochemical and cellular studies. Together, there is considerable experimental support for the proposed hypothesis that increased metabolic formation of toxic one-carbon metabolites in diabetic patients contributes importantly to the development of various clinical complications.

The formation of endocrinology as an independent medical discipline was preceded by the accumulation of medical experience during many centuries. The medicine of the ancient times was developing on the basis of continuity according to the basic principle «relata refero» (I tell what I have been told). Medicine and pharmacy in the countries of the ancient world had many similarities, but at the same time each civilization had its own geographical, cultural and historical particularities. The pathology of the thyroid was among the most studied pathologies in Ancient world. There are frequent mentions of the endemic goiter in the works of doctors from Ancient China, Ancient India and Ancient Greece.Although the link between iodine and the thyroid was not known, algae and dried sea sponges were using for treating swollen neck.There are many descriptions of neuroendocrine pathologies in historical sources, for example the Bible describes gigantism and the Talmud - hypoprolactinaemia.Special attention was paid to the study of diabetes mellitus, although the pathogenesis and treatment of the disease remained unknown until the 20th century.

Type 2 Diabetes Mellitus (T2DM) is one of the highly prevalence disorder and increasing day by day worldwidely. T2DM is a metabolic disorder, which is characterized by deficiency in insulin or resistance to insulin and thus increases the glucose levels in the blood. Various approaches are there to treat diabetes but still there is no cure for this disease. DPP-4 inhibitor is a privileged target in the field of drug discovery and provides various opportunities in exploring this target for development of molecules as antidiabetic agents. DPP-4 acts by inhibiting the incretin action and thus decreases the level of blood glucose by imparting minimal side effects. Sitagliptin, vildagliptin, linagliptin etc. are the different DPP-4 based drugs approved throughout the world for the treatment of diabetes mellitus. Cyanopyrrolidines, triazolopiperazine amide, pyrrolidines are basic core nucleus present in various DPP-4 inhibitors and has potential effects. In the past few years, researchers had applied various approaches to synthesize potent DPP-4 inhibitors as antidiabetic agent without side effects like weight gain, cardiovascular risks, retinopathy etc. This review will also emphasize the recent strategies and rationale utilized by researchers for the development of DPP-4 inhibitors. This review also reveals about the various other approaches like molecular modelling, ligand based drug designing, high throughput screening etc. are used by the various research group for the development of potential DPP-4 inhibitors.

Hippocratic doctrine of four humors and qualities is implicated to be a pioneer of modern endocrinology because of the concept of dyscrasia. Imbalance in humors causes disease. Unani scholars were aware of endocrinological disorders like endocrinologic syndrome (i.e., association of amenorrhea and galactorrhoea in a non-pregnant woman), castration, contraceptives techniques, infertility, obesity, diabetes etc., and also their mode of remedy, albeit with a phenomenological approach. Their understanding of the symptoms and signs related to endocrinologic syndromes, which were explained in detail in the recent account of the endocrine system, is presented here with historical chronology. The survey was carried out from the literature of the Unani system of medicine, and the same was analyzed from the observations reported in various indexed journals and reputed books. The paper details the account of endocrinologic syndrome from the Greek era to the end of the medieval ages. - Description of the endocrinal disorders is mentioned in Unani Medicine for centuries, albeit with a different name for the disease category.- According to Unani Medicine, this disease arises due to abnormal quality and quantity of humour.- Renowned Unani scholars like Hippocrates (370-460 BC), Aristotle (384-322 BC), Aretaeos of Kappadokia(81-96 AD), Galen (130-200 AD), Zakaria Razi (865-925 AD), Majusi (930-994 AD), Ibn-e-Sina (980-1037 AD), Albucasis (1013-1106 AD) and Ismail Jorjani (1042-1137 AD) also treated such ailments through Unani medicine (plant, mineral and animal origin drugs).-Majusi performed surgery of Goiter and mentioned in his treatise and recommended the method of surgery.-Albucasis performed the first successful thyroidectomy under opium (Papaver somniferum L.) sedation and simple ligatures and hot cautery in the name of 'elephantiasis' of the throat (goiter).- The principles of treatment in Unani medicine may provide a guide for better management of endocrinal disorders (e.g., hypothyroidism, hyperthyroidism, diabetes etc.).- The treatment in Unani medicine for various diseases/syndromes/signs, which are now likely associated with hormone dysfunction, can open up the new field of Unani therapeutics for these diseases for the exploration of better treatment options.

Diabetic Mellitus (DM) is a metabolic disorder that is concerning for people all over the world. DM is caused due to lack of insulin or ineffective production of insulin in the pancreas. A total of 463 million people were reported to have diabetes mellitus in 2019 and this number is predicted to rise up to 578 million by the year 2030 and 700 million by 2045. High blood sugar gives rise to many complications like diabetic retinopathy, diabetic nephropathy, atherosclerosis, hypercoagulability, cardiovascular disease, coronary heart disease, abdominal obesity, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease, foot damage, skin complications, Alzheimer's disease, hearing impairment, and depression. These life-threatening complications make diabetes more severe than other diseases. Many synthetic drugs have been developed, but still, a complete cure is not provided by any of the molecules. Continuous use of some synthetic agents causes severe side effects, and thus the demand for non-toxic, affordable drugs still persists. Traditional treatments have been an extremely valued source of medicine all over human history. These are extensively used throughout the world, indicating that herbs are a growing part of modern and high-tech medicines. The World Health Organization (WHO) has listed a total of 21,000 plants, which are used for medicinal purposes around the world. Among them, more than 400 plants are available for the treatment of diabetes. Despite the fact that there are many herbal drugs available for treating diabetes, only a small number of these plants have undergone scientific and medical evaluation to assess their efficacy. Trigonella foenum-graecum, Allium sativum, Caesalpinia bonduc, Ferula assafoetida,etc., are some of the medicinal plants used for antidiabetic therapy. The presence of phenolic compounds, flavonoids, terpenoids, and coumarins is responsible for the antidiabetic nature of the medicinal plants. These constituents have shown a reduction in blood glucose levels. Pycnogenol, acarbose, miglitol, and voglibose are some of the examples of marketed drugs, which are obtained from natural origin and used as antidiabetic drugs. The active principles derived from the plants work through many antidiabetic mechanisms, which include inhibition of α-glucosidase, α-amylase, and protein tyrosine phosphatase 1B activities. One of the major advantages of herbal drugs is the low level of side effects attributed to these medicines, and this attracted various researchers to develop new molecules for the treatment of diabetes. In this review, recent advances in the field of herbal drugs to treat diabetes, prevent secondary complications from arising due to diabetes, and various herbal molecules in different stages of clinical trials will be emphasized upon.

In this chapter we discuss the past, present and future of clinical biomarker development. We explore the advent of new technologies, paving the way in which health, medicine and disease is understood. This review includes the identification of physicochemical assays, current regulations, the development and reproducibility of clinical trials, as well as, the revolution of omics technologies and state-of-the-art integration and analysis approaches.

Type 2 diabetes mellitus (DM) is a lifelong metabolic disease, characterized by hyperglycaemia which gradually leads to the development and progression of vascular complications. It is recognized as a global burden disease, with substantial consequences on human health (fatality) as well as on health-care system costs. This review focuses on the topic of historical discovery and understanding the complexity of the disease in the field of pathophysiology, as well as development of the pharmacotherapy beyond insulin. The complex interplay of insulin secretion and insulin resistance developed from previously known "ominous triumvirate" to "ominous octet" indicate the implication of multiple organs in glucose metabolism. The pharmacological approach has progressed from biguanides to a wide spectrum of medications that seem to provide a beneficial effect on the cardiovascular system. Despite this, we are still not achieving the target treatment goals. Thus, the future should bring novel antidiabetic drug classes capable of acting on several levels simultaneously. In conclusion, given the raising burden of type 2 DM, the best present strategy that could contribute the most to the reduction of morbidity and mortality should be focused on primary prevention.

Giovanni Boccaccio's fatal disease(s) and cause of death have long remained a mystery. Now, for the first time, a thorough multidisciplinary reassessment has finally been carried out. By combining philological and clinical approaches, it is at last possible to suggest a solid retrospective diagnosis based upon a study of his correspondence, poetry and iconography, as well as references to his physical decay in coeval and later sources. It would appear that he suffered over the last three years of his life from hepatic and cardiac failure, conditions that resulted in edema and potentially even hepatic carcinoma. Focusing on an unusually well-documented case from the Middle Ages, this analysis of exceptionally high informative value reconstructs the symptoms of his medical conditions and finally permits us to clarify and explain the historical feaures, presentations and evolutionary history of the case at hand.

The field of personalized medicine that involves the use of measuring biomarkers in clinical samples is an area of high interest and one that has tremendous impact on drug development. With the emergence of more sensitive and specific technologies that are now able to be run in clinical settings and the ability to accurately measure biomarkers, there is a need to understand how biomarkers are defined, how they are used in clinical trials, and most importantly how they are used in conjunction with drug treatment. Biomarker approaches have entered into early clinical trials and are increasingly being used to develop new diagnostics that help to differentiate or stratify the likely outcomes of therapeutic intervention. Tremendous efforts have been made to date to discover novel biomarkers for use in clinical practice. Still, the number of markers that make it into clinical practice is rather low. In the next following chapters, we will explain the various classifications of biomarkers, how they are applied, measured, and used in personalized medicine specifically focusing on how they are used in de-risking the 10 plus years drug development process and lastly how they are validated and transformed into companion diagnostic assays.

This paper summarizes the impact that wars had on the history of nephrology, both worldwide and in the Ghent Medical Faculty notably on the definition, research and clinical aspects of acute kidney injury. The paper briefly describes the role of 'trench nephritis' as observed both during World War I and II, supporting the hypothesis that many of the clinical cases could have been due to Hantavirus nephropathy. The lessons learned from the experience with crush syndrome first observed in World War II and subsequently investigated over many decades form the basis for the creation of the Renal Disaster Relief Task Force of the International Society of Nephrology. Over the last 15 years, this Task Force has successfully intervened both in the prevention and management of crush syndrome in numerous disaster situations like major earthquakes.

Diabetes Mellitus is a common metabolic disorder presenting increased amounts of serum glucose and will cover 5.4% of population by year 2025. Accordingly, this review was performed to gather and discuss the stand points on diagnosis, pathophysiology, non-pharmacological therapy and drug management of diabetes this disorder as described in medieval Persian medicine. To this, reports on diabetes were collected and analyzed from selected medical and pharmaceutical textbooks of Traditional Persian Medicine. A search on databases as Pubmed, Sciencedirect, Scopus and Google scholar was also performed to reconfirm the Anti diabetic activities of reported herbs. The term, Ziabites, was used to describe what is now spoken as diabetes. It was reported that Ziabites, is highly associated with kidney function. Etiologically, Ziabites was characterized as kidney hot or cold dystemperament as well as diffusion of fluid from other organs such as liver and intestines into the kidneys. This disorder was categorized into main types as hot (Ziabites-e-har) and cold (Ziabites-e-barid) as well as sweet urine (Bole-e-shirin). Most medieval cite signs of Ziabites were remarked as unusual and excessive thirst, frequent urination and polydipsia. On the management, life style modification and observing the essential rules of prevention in Persian medicine as well as herbal therapy and special simple manipulations were recommended. Current investigation was done to clarify the knowledge of medieval scientists on diabetes and related interventions. Reported remedies which are based on centuries of experience might be of beneficial for- further studies to the management of diabetes.

The worldwide increase in the prevalence of Diabetes mellitus (DM) has highlighted the need for increased research efforts into treatment options for both the disease itself and its associated complications. In recent years, mesenchymal stromal cells (MSCs) have been highlighted as a new emerging regenerative therapy due to their multipotency but also due to their paracrine secretion of angiogenic factors, cytokines, and immunomodulatory substances. This review focuses on the potential use of MSCs as a regenerative medicine in microvascular and secondary complications of DM and will discuss the challenges and future prospects of MSCs as a regenerative therapy in this field. MSCs are believed to have an important role in tissue repair. Evidence in recent years has demonstrated that MSCs have potent immunomodulatory functions resulting in active suppression of various components of the host immune response. MSCs may also have glucose lowering properties providing another attractive and unique feature of this therapeutic approach. Through a combination of the above characteristics, MSCs have been shown to exert beneficial effects in pre-clinical models of diabetic complications prompting initial clinical studies in diabetic wound healing and nephropathy. Challenges that remain in the clinical translation of MSC therapy include issues of MSC heterogeneity, optimal mode of cell delivery, homing of these cells to tissues of interest with high efficiency, clinically meaningful engraftment, and challenges with cell manufacture. An issue of added importance is whether an autologous or allogeneic approach will be used. In summary, MSC administration has significant potential in the treatment of diabetic microvascular and secondary complications but challenges remain in terms of engraftment, persistence, tissue targeting, and cell manufacture.

It is increasingly apparent that not only is a cure for the current worldwide diabetes epidemic required, but also for its major complications, affecting both small and large blood vessels. These complications occur in the majority of individuals with both type 1 and type 2 diabetes. Among the most prevalent microvascular complications are kidney disease, blindness, and amputations, with current therapies only slowing disease progression. Impaired kidney function, exhibited as a reduced glomerular filtration rate, is also a major risk factor for macrovascular complications, such as heart attacks and strokes. There have been a large number of new therapies tested in clinical trials for diabetic complications, with, in general, rather disappointing results. Indeed, it remains to be fully defined as to which pathways in diabetic complications are essentially protective rather than pathological, in terms of their effects on the underlying disease process. Furthermore, seemingly independent pathways are also showing significant interactions with each other to exacerbate pathology. Interestingly, some of these pathways may not only play key roles in complications but also in the development of diabetes per se. This review aims to comprehensively discuss the well validated, as well as putative mechanisms involved in the development of diabetic complications. In addition, new fields of research, which warrant further investigation as potential therapeutic targets of the future, will be highlighted.

Historically, insulin is best known for its role in peripheral glucose homeostasis, and insulin signaling in the brain has received less attention. Insulin-independent brain glucose uptake has been the main reason for considering the brain as an insulin-insensitive organ. However, recent findings showing a high concentration of insulin in brain extracts, and expression of insulin receptors (IRs) in central nervous system tissues have gathered considerable attention over the sources, localization, and functions of insulin in the brain. This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation. This review also considers the neuromodulatory and neurotrophic effects of insulin, resulting in proliferation, differentiation, and neurite outgrowth, introducing insulin as an attractive tool for neuroprotection against apoptosis, oxidative stress, beta amyloid toxicity, and brain ischemia.

The assessment of kidney damage is a challenge and must incorporate assessment of the functional capacity of the kidney, as well as a comprehensive understanding of the kidney's role. Multiple parameters have been used for many years to measure renal functionality to assess renal damage. It is astonishing that, beside histopathology, the most common traditional parameters are serum based. However, urine is also used to obtain additional information regarding the health status of the kidneys. Since 2008, several novel urinary protein biomarkers have been qualified by the US FDA and the European Medicines Agency in conjunction with the Predictive Safety Testing Consortium in a specially developed qualification process. Subsequently, the Pharmaceuticals and Medical Devices Agency accepted the qualification of these seven urinary biomarkers. This review will give an overview of the state-of-the-art detection based on urinary biomarkers, which will enhance toxicological research in the future. In addition, the qualification process that leads to acceptance of these biomarkers will be described because of its uniqueness and importance for the field of biomarker research.

Laboratory medicine has evolved from basic scientific observation and good experimental practice, with a strong emphasis on establishing the mechanisms of disease processes, linked with biomarker discovery, and development of analytical technologies. That evolution is set to move on apace with the mapping of the human genome. However, laboratory medicine is not solely based on robust basic science, but also on the translation of that knowledge into establishing the clinical utility of a marker, translation into evidence of the impact on health outcomes, as well as transformational change to integrate this new knowledge into the delivery of better care for patients. This translational research and the focus on transformational change are crucial in demonstrating value-for-money in the laboratory medicine service.

Acute kidney injury (AKI), a recently defined clinical entity, is an ailment that has afflicted humans from time immemorial. Its emergence as a disease follows by 50 years that of acute renal failure (ARF) after the Second World War. The medical model of ARF emerged as studies of the kidney in traumatic shock unraveled the pathophysiology of the disease and focused on its treatment with hemodialysis. ARF was reframed as AKI, based on the model that had been developed for chronic kidney disease, to incorporate the accrued epidemiologic data and present it as a public health model of disease that is potentially preventable and treatable at earlier stages of the disease.

The search for biomarkers and their evaluation by scientists and clinicians is of paramount importance if we are going to improve health care. In this paper we discuss the history of the discovery of biomarkers for renal and cardiac injury. We also summarize the use of biomarkers in preclinical evaluation in experimental animals and in patients to help diagnose or monitor a disease, predict outcome or to evaluate a therapeutic intervention. The need for validated biomarkers of tissue injury or disease that must be easy to analyse rapidly, preferably at the bedside, is essential if clinical decision making is to be optimally affected by their use.

The science of looking at the urine for diagnostic purposes, uroscopy, is as ancient as disease. Throughout history, urine, the first bodily fluid to be examined, has continuously and persistently provided medicine with an increasing body of knowledge about the workings of the inner body. For most of its history, uroscopy was a visual science; this focus peaked in the Middle Ages, when the vessel used to examine urine, the matula, became a symbol of the medical profession. Over time, the practice of uroscopy spread into the hands of quacks and apothecaries, who prescribed and sold their potions by merely looking at the urine. The consequent reformation measures of the 16th and 17th centuries coincided with the first attempts at analyzing the contents of urine. As a result, many of the chemical components now reported in metabolic profiles were first analyzed and identified in urine during the first half of the 18th century. In the process, what started as a science that bordered on divination laid the foundations of chemical analysis and spawned the disciplines of urology, endocrinology, and, after the use of urine in clearance studies, nephrology. The analytical methods and remarkable achievements of each of these disciplines have increased the value of examining urine. A renaissance of this oldest diagnostic tool of medicine is now under way in the proteomic profiling and detection of biomarkers in the urine, an approach which promises to further extend the merits of the unbroken tradition of looking at the urine.

Chronic food shortage and malnutrition have been the scourge of humankind from the dawn of history. The current worldwide epidemic of obesity, now recognized as a public health crisis, is barely a few decades old. Only after the technological advances of the eighteenth century did a gradual increase in food supply became available. The initial effect of these advances in improved public health and amount, quality, and variety of food was increased longevity and body size. These early favorable outcomes of technological advances notwithstanding, their incremental effect since the Second World War has been an overabundance of easily accessible food, coupled with reduced physical activity, that accounts for the recent increased prevalence of obesity. Obesity as a chronic disease with well-defined pathologic consequences is less than a century old. The scarcity of food throughout most of history had led to connotations that being fat was good, and that corpulence and increased "flesh" were desirable as reflected in the arts, literature, and medical opinion of the times. Only in the latter half of the nineteenth century did being fat begin to be stigmatized for aesthetic reasons, and in the twentieth century, its association with increased mortality was recognized. Whereas early reports listed obesity as a risk factor for mortality from "chronic nephritis," the subsequent recognition of the more common association of obesity with diabetes, hypertension, and heart disease altered the listings and questioned its being a risk factor for kidney disease. An enlarging body of evidence, accrued over the past decade, now indicates a direct association of obesity with chronic kidney disease and its outcomes.