Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

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Central sensitization: implications for the diagnosis and treatment of pain.

Background
The Danish National Patient Registry (DNPR) is one of the world’s oldest nationwide hospital registries and is used extensively for research. Many studies have validated algorithms for identifying health events in the DNPR, but the reports are fragmented and no overview exists.

/pdf/the-danish-national-patient-registry-a-review-of-content-1tblzc3eff.pdf

The Danish National Patient Registry: a review of content, data quality, and research potential.

Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made with regard to the development of electrospinning methods and engineering of electrospun nanofibers to suit or enable various applications. We aim to provide a comprehensive overview of electrospinning, including the principle, methods, materials, and applications. We begin with a brief introduction to the early history of electrospinning, followed by discussion of its principle and typical apparatus. We then discuss its renaissance over the past two decades as a powerful technology for the production of nanofibers with diversified compositions, structures, and properties. Afterward, we discuss the applications of electrospun nanofibers, including their use as "smart" mats, filtration membranes, catalytic supports, energy harvesting/conversion/storage components, and photonic and electronic devices, as well as biomedical scaffolds. We highlight the most relevant and recent advances related to the applications of electrospun nanofibers by focusing on the most representative examples. We also offer perspectives on the challenges, opportunities, and new directions for future development. At the end, we discuss approaches to the scale-up production of electrospun nanofibers and briefly discuss various types of commercial products based on electrospun nanofibers that have found widespread use in our everyday life.

Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications

Irritable bowel syndrome

Abstract As the function of the gastrointestinal tract is to a large degree mechanical, it has become increasingly popular to acquire distensibility data in motility research based on various parameters. Hence it is important to know on which geometrical and mechanical assumptions the various parameters are based. Currently, compliance and tone derived from pressure‐volume curves are by far the most often used parameters. However, pressure‐volume relations obtained in tubular organs must be carefully interpreted as they provide no direct measure of luminal cross‐sectional area and other variables useful in plane stress and strain analysis. Thus, erroneous conclusions concerning tissue distensibility may be deduced. Other parameters, such as wall tension, stress and strain, give more useful information about mechanical behaviour. Distensibility data procure significance in fluid mechanics and in the study of tone, peristaltic reflexes, and mechanoreceptor kinematics. Such data are needed for the determination of the interaction between stimulus, electrical responses in neurons and the mechanical behaviour of the gut. Furthermore, from a clinical perspective, investigation of visco‐elastic properties is important because GI diseases are associated with growth and remodelling. For example, prestenotic dilatation, increased collagen synthesis, dysmotility and altered distensibility are common features of obstructive diseases. The purpose of this review is to discuss the physiological and clinical importance of acquiring biomechanical data, distensibility parameters and interpretation of these results and their associated errors. We will also discuss some aspects of the relationship between morphology, growth and biomechanics. Finally, we will outline a number of techniques to study the mechanical properties of the GI tract.

Biomechanics of the gastrointestinal tract

As the function of the gastrointestinal tract is to a large degree mechanical, it has become increasingly popular to acquire distensibility data in motility research based on various parameters. Hence it is important to know on which geometrical and mechanical assumptions the various parameters are based. Currently, compliance and tone derived from pressure-volume curves are by far the most often used parameters. However, pressure-volume relations obtained in tubular organs must be carefully interpreted as they provide no direct measure of luminal cross-sectional area and other variables useful in plane stress and strain analysis. Thus, erroneous conclusions concerning tissue distensibility may be deduced. Other parameters, such as wall tension, stress and strain, give more useful information about mechanical behaviour. Distensibility data procure significance in fluid mechanics and in the study of tone, peristaltic reflexes, and mechanoreceptor kinematics. Such data are needed for the determination of the interaction between stimulus, electrical responses in neurons and the mechanical behaviour of the gut. Furthermore, from a clinical perspective, investigation of visco-elastic properties is important because GI diseases are associated with growth and remodelling. For example, prestenotic dilatation, increased collagen synthesis, dysmotility and altered distensibility are common features of obstructive diseases. The purpose of this review is to discuss the physiological and clinical importance of acquiring biomechanical data, distensibility parameters and interpretation of these results and their associated errors. We will also discuss some aspects of the relationship between morphology, growth and biomechanics. Finally, we will outline a number of techniques to study the mechanical properties of the GI tract.

https://www.springer.com/productFlyer_978-1-85233-520-5.pdf?SGWID=0-0-1297-2180540-0

Biomechanics of the Gastrointestinal Tract

The invention comprises a system, catheter (20) and method for measuring the cross-sectional areas and pressure gradients in any hollow organ, such as, for example, blood vessels. One embodiment of such a system includes: an impedance catheter (20) capable of being introduced into a targeted site; a solution delivery source (106); a constant current source; a balloon inflation control device (105); and a data acquisition and processing system (100) that receives conductance and/or pressure gradient data from the catheter (20) and calculates the cross-sectional area of the targeted site. In one embodiment, the catheter (20) has an inflatable balloon along its longitudinal axis, thereby enabling the breakup of any materials causing stenosis at the targeted site and/or distention and delivery of an optional stent into the targeted site.

System and method for measuring cross-sectional areas and pressure gradients in luminal organs

Objective: To determine whether neuromuscular dysfunction of the esophagus causes chest pain in patients in whom no disease is found on cardiac work-up, upper gastrointestinal endoscopy, esophageal...

Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.

Abdominal pain is of frequent occurrence, even in the normal population (1), and pain is probably the most prevalent symptom in the gastroenterology clinic. Consequently, characterization of gut pain is one of the most important issues in the diagnosis and assessment of organ dysfunction, and research leading to a better insight into pain mechanisms in the gastrointestinal (GI) tract will improve the treatment of patients (2). In clinical work, characterization of pain is confounded by many other symptoms caused by the diseases, such as complaints relating to psychological, cognitive and social aspects of the illness. Moreover, many diseases are typically associated with systemic reactions such as fever and general malaise, which can be difficult to distinguish from the symptoms relating to pain. Finally, the patients are typically treated with different therapeutic interventions that may cause sedation and changes in gut motor function. All such confounders can influence the perception of pain, making its assessment in clinical studies difficult. A possible way to overcome this problem is to use experimental models, where the investigator can control the pain ‘input’ e.g., the nature, localization, intensity, frequency and duration of the stimulus, and provide reproducible measures of the ‘output’ e.g., the psychophysical, behavioural or the neurophysiological response (3, 4). Experimental models have been used in different animal species, where the investigators can study the neuronal activity in anaesthetized or spinalized animals directly, with invasive techniques or with assessment of behaviour (for review, see (5)). The neurobiology of the pain system differs, however, between the species, and this limits the interpolation of findings from animal studies to man. Moreover, pain is the net effect of complex multidimensional mechanisms that involve most parts of the central nervous system. Therefore, although nociceptive reflexes or electrophysiological recordings from selected pathways in the animal nervous system are important in basic research, the central pain mechanisms and associated complex reactions are typically suppressed, and animal experiments can only to some degree reflect the experience of clinical pain in humans. Consequently, the interest in human experimental pain studies has increased rapidly during the last decade (6), and also in gastroenterology the focus has been on developing methods for experimental induction and assessment of human pain.

Hans Gregersen

Papers

Biomechanics of the gastrointestinal tract

Biomechanics of the Gastrointestinal Tract

System and method for measuring cross-sectional areas and pressure gradients in luminal organs

Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.

Experimental pain in gastroenterology: a reappraisal of human studies