A. Ramon. United States Coast Guard Academy.

Charles Allen’s Trea- policies to reduce harmful use of 40 purchase tadora 20 mg without prescription best erectile dysfunction vacuum pump, 46 order tadora 20 mg fast delivery doctor for erectile dysfunction in mumbai, affordability of 21 proven tadora 20mg erectile dysfunction caused by supplements, 64, 68, 69 conditions tise of 1685/6. Palaeontology: risk factors for universal access to 21, 59, 66, 105 global burden of 9, 13, 84 coverage schemes in the developing world: a review of the exist- early Neolithic tradition of dentistry. The history of oral hygiene products: how far have oral cancer 26, 27, 29, 39, 46, 47, 93 gingivitis 22 number affected by 16, 54 erage: a unique policy opportunity for oral health. Berlin: Quintessence; periodontal disease 22, 25, 41, 46, 92 of 21 Paris V, Devaux M, Wei L. Musée Virtuel de l’art dentaire Basic Package of Oral Care 64 signs of in oral health 13, 30 challenges in 71–77 Somkotra T, Detsomboonrat P. Thechnical report for the post-2015 sustainable development data see disease surveillance in disease burden 14, 52, 54–55, 95 84, 92 1994;3:13-15. The World Health Report: Health sys- dental education 71, 72–73, 96, 102 oral health 55 oral healthcare 60–66 tems fnancing: the path to universal coverage. Available from: expenditure on 56, 57 policies to address 51, 52, 84, 95 continuum 64, 65 www. Akash / Panos; dentition 10–11, 92 Minamata Convention on Mercury (2013) 66, 68, 92, 96, 99 Tomar S et al, 2010. Guidelines for successful 33 Winds of Hope / Philippe Rathle; Winds of Hope / Philippe implementation. Future Use of Materials for Dental Panos; 58 4774344sean / iStockphoto; 70 kevinruss / iStockphoto; lack of 16, 22, 56, 84 13, 14, 25, 39, 41, 80, 81 Restoration. Over the years, it has developed programmes, policies to address 40, 60, 94 toothbrushing 10, 68, 69 initiatives, campaigns, policies and congresses, always with a view to occu- social gradient see inequalities toothpaste see fuoride strategies to combat pying a space that no other not-for-proft group can claim. They are generally related to the same preventable risk factors associated with over 100 noncommu- nicable diseases. Yet, international attention to oral diseases does not match the high number of cases, nor the impact these diseases have on individuals, populations and society. The frst edition of the Oral Health Atlas focused on ‘mapping a neglected global health issue’. The new edition of this atlas continues to highlight the extent of the problem worldwide and refects on policies and strategies addressing the global burden of oral disease. The Challenge of Oral Disease – A call for global action is a valuable resource for public health experts, policy makers, the oral health profession and anyone with an interest in oral health. The wide range of oral health topics presented include: • the impact and burden of oral diseases, such as tooth decay, periodontal disease, oral cancer and more • major risk factors and the common risk factor approach • inequalities in oral health • oral disease prevention and management • oral health challenges • ensuring oral health is on global health and development agendas. Its main feature is the combination of symptoms, such as fever higher than 39°C, cutaneous rash during fever peaks, joint or muscle pain, lymph node hypertrophy, increase of white blood cells (especially polymorphonuclear neutrophils) and abnormalities of liver metabolism. None of these signs is sufficient to establish the diagnosis, and several other diseases (notably infectious or neoplastic diseases) may produce similar symptoms. The evolution of the disease is difficult to predict; it may be limited to only one flare or may recur over a period of several months or years. Treatments have 2 objectives : - To limit the intensity of the symptoms of the disease. As a • trabscient skin rash on, the trunk and limbs result, case identification is difficult and the appearing during the fever spikes; numbers available on the frequency of this • muscle pain; disease should be viewed with caution. Many analogies exist between the adult In France and juvenile forms; however, their treatments The incidence has been estimated between 1 differ. By definition, adult onset form begins after and 2 new cases per million inhabitants per year. Sometimes the juvenile Different studies have shown that the frequency form is not diagnosed, because the symptoms of the disease is the same for men and women, can disappear definitively after several weeks, or slightly higher for women than men. As a general arthritis or systemic lupus erythematosus; rule, this eruption is not itchy; • inflammatory diseases, such as polymyositis • sore throat. Thoracic pain, some forms of deep abscesses; suggestive of effusion (presence of liquid) in the • neoplastic diseases, such as lymphomas or pleura (envelope surrounding the lungs) or some cancers. Evolution When they are present, these signs, are often The evolution of the disease is unpredictable. In discrete and usually only detected by the other words, when the physician announces the physician during the physical examination. Some patients experience only one flare of the disease, which regresses with symptomatic treatment in several weeks or months. The patient can also be anemic Some patients can have more frequent flares, (low red blood cells and low hemoglobin recurring at intervals of several weeks or months level) and have a high number of platelets. More generally, the acid), diclofenac, indomethacin, naproxen, search for signs of bacterial or viral infection ketoprofen, celecoxib, refecoxib,. When antibiotics are prescribed, to improve the inflammation caused by the they are ineffective. In certain cases (approximately 20%), these agents are responsible for a As for the clinical signs, it is important to complete relief of symptoms. Even if the notion of predisposing generally used within the framework of their background has been suggested, no familial marketing authorizations. As a consequence, no genetic counseling is necessary should a The second category of treatments corresponds pregnancy be desired. Manifestations and complications in 65 cases mg/kg/day), then progressively reduced over in France. It was recently estimated that since 1924, vaccinations have prevented 103 million cases of childhood infection, representing approximately 95 percent of infections that would have occurred, including For every $1 the U. Ensuring consistency between cause-specific estimates and all-cause mortality estimates. It is a systematic, scientific effort to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geographies for specific points in time. To ensure a health system is adequately aligned to a population’s true health challenges, policymakers must be able to compare the effects of different diseases that kill people prematurely and cause ill health and disability. More information about each of these groups is listed below in the “Roles and Responsibilities” Section below. Providing expertise, access to, and feedback on the data used for all-cause mortality estimation. Providing expertise and feedback on the results generated for the all-cause mortality envelope. Providing expertise, access to, and feedback on the data used for the analyses of specific diseases, injuries, risk factors, or impairments. Providing expertise and feedback on the validity and interpretation of results generated for specific diseases, injuries, risk factors, or impairments. Providing expertise, access to, and feedback on the data used for country-specific results. Providing expertise and feedback on the validity and interpretation results generated for a specific country. Where possible, engaging even more closely to generate subnational estimates for specific countries that are consistent with the overall global and national estimates produced annually. The data used and the analytic strategies applied to generate the results will be consistent with these principles and assumptions.

Recognition of vironment order tadora 20 mg visa erectile dysfunction anxiety, resources and infrastructure should be promo- the importance of translational research for the integra- ted tadora 20 mg low price erectile dysfunction even with cialis. Go- cifc intended use in the context of research and de- vernments buy cheap tadora line erectile dysfunction injections cost, charities, not-for-proft and private funders velopment relating to pharmaceuticals. This process should join forces to foster a collaborative culture in can also be used to evaluate and validate biomarkers. Continuity tegic Research Agenda entitled ‘The right prevention of high quality research lines has to be ensured by ins- and treatment for the right patient at the right time’ talling sustainable funding schemes that allow basic re- was published in 2013 (http://www. Member States and other countries tries of health and research; institutions for public health and health insurance, healthcare providers, The Academy of Finland’s research programme Perso- societies, patient organisations, ethics committees, nalised Health(2014–2019,http://www. In addition, the programme will look into the me- devices from the preclinical phase into clinical trials. In dical, treatment-related, technological, judicial, ethical, order to facilitate research in this feld methods and social and societal issues and impacts relating to data tools for integrating data from research need to be im- generation, collection, storage and use. This designation is aimed at ofering new oppor- cancer, diabetes, dementia, and infectious diseases; tunities for conducting translational cancer research, (2) to identify risk factors; (3) to highlight efective thus helping to optimise and hasten the production forms of prevention; and (4) to identify options for of new knowledge and promote its dissemination and the early detection of diseases. The French Alliance for Re- 200,000 people aged between 20 and 69 from across search in Life Sciences (Aviesan) has set up two strate- Germany will be medically examined and questioned gic valorisation felds on biomarkers and companion on their living habits (e. In the cour- relevant players across the value chain to: (1) identify se of their observation over a period of 10–20 years, the teams involved in biomarker research and validati- some of the participants are certain to develop di- on (pathological or technological); (2) make an inven- seases, which can then be correlated with the data tory of biomarkers and order them according to their collected. It is a unique database of personal of the analysis) and to ofer support in all project mo- and family medical histories collected during three des; (3) work alongside pharmaceutical, diagnostics intensive studies. In the third phase genetic data is and device manufacturers to assess the development being collected, and will be combined with clinical re- stage and level of interaction needed between these cords and cancer, stroke and death registries. These institutes are collaborative structu- on issues concerning business models and reimburse- res that bring together basic research groups from ment based on real cases and an exact defnition of academia and clinical research groups from hospi- ‘clinical utility’. Strategy Board) has invested £50m over the past fve years through a stratifed medicine innovation In Canada, as discussed in Challenge 1, a Genome Ca- platform – see Challenge 1 above for details. Following a competitive on a small scale how routine testing of patients’ tu- call, 17 such projects – for a total budget of 165 MioC$ mours could be scaled up to provide a national ser- over four years – have been funded. More rapid introduction of inno- vel molecule, which inevitably leads to the optimisati- vations into health systems needs to be based on regula- on of processes, an increase in efciency and security tory and reimbursement pathways that take into account and a decrease in adverse events, both in quantity and evolving knowledge on safety, efcacy, efciency and the quality. Moreover, there is a reduction in the number of necessary conditions of the health system that allow the patients in clinical studies, due to the inclusion of their promise of the innovation to be realised. For these appro- genotype and phenotype, resulting in an optimisation aches – both for drug and non-pharmaceutical products of resources and, most importantly, a contraction in the – processes need to be able to evaluate the use of in vitro time needed. But the resulting high cost and the lack and companion diagnostics, innovative clinical trial de- of knowledge in clinical outcomes if such a therapeutic signs and the balance between the inherent higher uncer- proposition were to be extended to a larger number tainty due to smaller sample size of target groups and the of patients will require the pharmaceutical, technolo- contrary inherent lower uncertainty due to higher impact gical and biotechnological industries to come up with or efectiveness on target groups. Another, at least equal- process in order to successfully bring innovation to the ly important, challenge for European regulators is the market (Rosenkötter et al. The inclusion of economic dimensions into macy especially in the case of multi-morbidity. For this growing group of tizens as well as patients will be signifcantly confronted patients, ways must be identifed to evaluate benefts and with it in ‘digital health’ (by information and training), in risks of medication which are usually tested in younger and the ‘internet of things’ (by devices) and in social networks healthier populations and where the evidence base is weak. Mo- plicit examination of what is necessary in order to allow reover, approaches for individualisation of drug therapy in the promise of the innovation to be realised. For example, the light of several comorbidities and patients’ preferences well-defned patient pathways are needed for the appro- should be tested and validated. Participation of patients and their commendations empowerment must play a crucial role in improving adhe- rence; otherwise the best drugs will not be efective. A combination of beneft–risk evaluation with real-time data and the use of observational, epidemiological or in Research on regulatory and legal issues should be sup- silico studies to demonstrate efectiveness even on indi- ported in order to update and adapt current regulations. These evaluations le regulatory procedure across all regulators, taking into will also enable post-marketing surveillance to spot rare account ethical, legal and social aspects. This would lead adverse events and include spontaneous reporting and to reduced costs and fewer administrative hurdles and analysis of electronic health records. Those approaches often include a combina- without considering the global perspective. These new models are based on a con- der collaboration in research and development tinuous adaption of the use of new technologies to the using an ‘Open Innovation’ approach. European bi-directional fow of ideas and interchange between harmonisation in these areas would also facilitate interna- companies. Innovation in lic, private and user partnerships, seems to be particular- the area of rare diseases has recently benefted from such ly interesting for enabling the introduction of promising international coordination through the International Rare innovation, where the added value is of high plausibility. The rare di- tems accompanied by research that reduces the inherent sease feld ofers many ‘lessons learned’ and can help to uncertainties under real-world conditions. Peer reviewed ensure that similar international structures can be esta- collaborative research using open data is a model that blished. Encourage a systematic early dialogue between innovators, patients and decision-makers th- In this context translational projects closer to the pati- roughout all regulatory steps to provide guidan- ent/market should be driven by the end-users’ needs. Companies are This recommendation is closely allied to the revision of the hesitant to access the market due to the limited under- regulatory and legal framework to produce a clearer and standing of certifcation, validation and regulations: for harmonised approach with interconnected components. Innovators and companies should be research, even at an early stage, considers the regulatory encouraged to seek guidance early in relation to options and reimbursement evaluation needs, e. This will importance to involve patients in this dialogue, especially facilitate access to resources and competences, both of in terms of defning endpoints, patient-relevant outcomes which are lacking among the diferent actors involved in and intended comparative value. Eu- tial approval in a well-defned patient subgroup with comed) and biotechnology industries (e. It is open to industry, acade- including the prevention of an illness before its onset. It ofers a safe harbour and open posed to death), but their patients might even experien- dialogue with expert regulators who ofer their perso- ce absolute recovery. Market entry pathways have to be ad- vative development methods or trial designs), ofer an apted in order to assure a safe, efective and competitive ofcial response to very specifc scientifc questions environment for patients and industry. In total, ten early dialogues is to carry out basic and translational research as well are planned with the aim to conduct seven on drugs as the instruction and distribution of new genomics and three on medical devices. In this sense, some major drivers Healthcare should be considered: a) the technology itself; b) the sys- tem and its organisation (including its workforce); and c) Introduction the interaction between the system and the client. There are today several policy tools to manage the difusi- on of innovations in healthcare, one of which is payment The technology or group of technologies, if we consider tre- mechanisms. The challenges faced by payment autho- atments and companion diagnostics, by itself ofers bene- rities are manifold. How can promising innovations be fts that are linked to its inherent characteristics: the capaci- driven forward while avoiding the difusion of undesirab- ty of creating tailored solutions that increase the safety and le ones? How can the execution of studies required for efcacy of treatments and the generation of further data sound reimbursement decision-making be encouraged?

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All medications should have an indication cheap tadora amex erectile dysfunction karachi, and if they do not order 20 mg tadora with visa erectile dysfunction caused by vicodin, an evaluation is needed to see if the medication is necessary purchase tadora with a visa erectile dysfunction treatment after prostate surgery. Discontinuation of unnecessary medications is reasonable for most drugs, but some may need to be tapered off to prevent any adverse drug withdrawal events. It is also important to determine if a new medication is being used to treat the side effects of another medication. Although sometimes a prescribing cascade is necessary (eg, potassium supplementation in a patient receiving a diuretic), many times it adds an unnecessary burden to the patient’s already complicated medication regimen. Existing therapies should also be evaluated to determine if they need to be continued or if optimization could occur. Nonphar- macologic therapy, such as diet and exercise, should be considered whenever possible. If a medication is determined to be necessary, health care providers need to consider the medication’s pharmacokinetic and pharmacodynamic properties, side effect profile, and current hepatic and renal function for accurate dosing. Medication cost, patient preference, and potential for drug-drug and drug-disease interactions should also be considered in prescribing. Reasonable therapeutic goals and monitoring parameters will help guide therapy to prevent unwanted side effects. It is also wise for health care providers to create their own personal formularies where they become very familiar with prescribing a few drugs. Simplifying medication regimens as well as educating patients regarding medications can improve adherence. When drug therapy has been titrated to ideal doses, try to combine medications into single pills to reduce pill burden. Indication Ensure each medication has an indication and a defined, realistic therapeutic goal. List List the name and dose of each medication in the chart and share it with the patient and/or caregiver. Individualize Apply pharmacokinetic and pharmacodynamic principles to individualize medication regimens. Avoid potentially dangerous interactions, such as those that can increase the risk for torsades de pointes. Educate Educate the patient and caregiver regarding pharmacologic and nonpharmacologic treatments. Discuss expected medication effects, potential adverse effects, and monitoring parameters. Medications should start at lower than usual doses and be titrated slowly, often referred to as “start low, go slow. Discuss expected medication effects, potential adverse effects, and drug-drug interactions and monitoring parameters. Providers should evaluate all existing medications at each patient visit for appropriateness and weigh the risks and benefits of starting new medications to minimize polypharmacy. Administration on Aging of the United State Department of Health and Human Services. Recent patterns of medication use in the ambulatory adult population of the United States: The Slone survey. Potentially inappropriate medication use among elderly home care patients in Europe. Polypharmacy, length of hospital stay, and in-hospital mortality among elderly patients in internal medicine wards. Polypharmacy and inappropriate prescrib- ing in elderly internal-medicine patients in Austria. Polypharmacy in nursing home residents in the United States: results of the 2004 National Nursing Home Survey. Inappropriate medication prescribing in residential care/assisted living facilities. The impact of clinical pharmacists’ consultations on physicians’ geriatric drug prescribing. Effects of geriatric evaluation and management on adverse reactions and suboptimal prescribing in the frail elderly. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. Polypharmacy, adverse drug-related events, and potential adverse drug interactions in elderly patients presenting to an emergency department. Polypharmacy in the elderly: Clinical challenges in emergency practice: Part 1: Overview, etiology, and drug interactions. Clinically important drug-disease interactions and their prevalence in older adults. Measurement, correlates, and health outcomes of medication adherence among seniors. Clinical consequences of polypharmacy in the elderly: expect the unexpected, think the unthinkable. A pharmacoepidemiologic study of community- dwelling, disabled older women: factors associated with medication use. Association of polypharmacy with nutritional status, functional ability and cognitive capacity over a three-year period in an elderly population. Consequences of falling in older men and women and risk factors for health service use and functional decline. Potentially inappropriate prescribing and cost outcomes for older people: a national population study. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability. Fall-risk screening test: a positive study of predictors for falls in community-dwelling elderly. Effects of central nervous system polyphar- macy on falls liability in community-dwelling elderly. Older adults medication use 6 months before and after hip fracture: A population-based cohort study. Reduction of high-risk polypharmacy drug combinations in patients in a managed care setting. A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy. Cost avoidance, acceptance, and outcomes associated with a pharmaco- therapy consult clinic in a Veterans Affairs Medical Center. Polypharmacy management in Medicare managed care: changes in prescribing by primary care physicians resulting from a program promoting medication reviews.

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This marriage of classical microbiology with gnotobiotic and sequencing technology will likely prove a powerful tool in the next decade’s attempt to understand how specific pathways are implicated in disease phenotypes cheap 20mg tadora otc erectile dysfunction doctors in texas. Conclusion The gut ecosystem is very complex buy tadora 20mg free shipping erectile dysfunction age 25, but there has been substantial and exciting recent progress in development of genomic and bioinformatics tools that can allow for delineation of that complexity buy cheap tadora 20mg online erectile dysfunction university of maryland. The initial phase of the Human Microbiome Project focused on utilizing sequencing to characterize variation in healthy adults. As we move into the next phase of the study of the human microbiome, a central focus will be on determining which microbial taxa, genes and pathways are implicated in disease. Careful design of clinical trials and experiments in animal models will be required to overcome the substantial background variation in the gut microbiome and separate confounding variables that are often closely related to the disease categories of interest. A central challenge will be the integration of different types of “omics” data to produce mechanistic descriptions of how host and microbe together produce phenotype. Zhu Q, Gao R, Wu W, Qin H (2013) The role of gut microbiota in the pathogenesis of colorectal cancer. Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Human Microbiome Project Consortium (2012) A framework for human microbiome research. Yang X, Xie L, Li Y, Wei C (2009) More than 9,000,000 unique genes in human gut bacterial community: estimating gene numbers inside a human body. Dai L, Gao X, Guo Y, Xiao J, Zhang Z (2012) Bioinformatics clouds for big data manipulation. Parameswaran P, Jalili R, Tao L, Shokralla S, Gharizadeh B et al (2007) A pyrosequencing- tailored nucleotide barcode design unveils opportunities for large-scale sample multiplexing. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada Thet al (2011) Enterotypes of the human gut microbiome. Koren O, Knights D, Gonzalez A, Waldron L, Segata N et al (2013) A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets. Wu G, Lewis J, Hoffmann C, Chen Y-Y, Knight R et al (2010) Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags. Proc Natl Acad Sci U S A 108:6252–6257 Chapter 3 The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control John B. The myenteric plexus forms a continuous network that extends from the upper esophagus to the internal anal sphincter. Submucosal ganglia and connecting fiber bundles form plexuses in the small and large intestines, but not in the stomach and esophagus. Voluntary control of defe- cation is exerted through pelvic connections, but cutting these connections is not life-threatening and other functions are little affected. This review is confined to discussion of monogastric mammals, in which most investigations have been done and which are arguably most relevant to human. The Extrinsic Innervation of the Gastrointestinal Tract Connections between the gut and the central nervous system can be conveniently classified as vagal, spinal thoracolumbar and spinal lumbosacral. Each of these includes afferent (sensory) innervation and efferent (motor innervation). The effer- ent pathways contain pre-enteric neurons that end within enteric ganglia and control or modify the activities of enteric neurons. Vagal Innervation The human abdominal vagus contains about 40,000–50,000 axons [1]. These fibers provide a sensory innervation and efferent (motor) control pathways for the upper gastrointestinal tract and digestive organs (Fig. The afferents include mucosal mechanoreceptors, chemoreceptors and tension receptors in the esophagus, stom- ach and proximal small intestine, and sensory endings in the liver and pancreas. There is a less prominent vagal afferent innervation of the distal small intestine and proximal colon. This indirect chemoreceptor activation is important for the detection of nutrients and 42 J. The functions that are regulated by the vagal sensory innervation include appetite and satiety, esophageal propulsion, gastric volume, contractile activity and acid secretion, contraction of the gallbladder and secretion of pancreatic enzymes. They were originally described in the esophagus and shown to be of vagal origin [5], and were subsequently demonstrated throughout the gastrointestinal tract [6]. Firing rates diminished within the first 2–3 s, but were maintained above the background level for the duration of the stimulus, thus these are partially adapting mechanoreceptors. They almost certainly correspond to the low threshold tension receptors that have been known for a long time, and, in the case of the stomach, probably signal filling [9, 10]. Three types of vagal mucosal afferent have been identified: gastric mucosal afferent endings, afferents supplying villi in the small intestine (villus afferents) and afferents supplying intestinal crypts (crypt afferents) [13]. The axons of gastric mucosal afferents branch extensively in the mucosa to provide an innervation that lies close beneath the epithelium; there are commonly flattened structures (lamel- lae) near the endings of these branches [13]. Gastric mucosal receptors are responsive to low intensity stroking of the mucosa, but not to muscle stretch or contraction, and are also sensitive to chemical stimuli, such as acid in the lumen [14–16]. Solid food is titurated in the stomach into smaller particles that are able to pass through the pylorus [17]. Experiments in which the antral mucosa was separated from the underlying muscle, a procedure that abolishes vago-vagal reflexes, suggest that mucosal mechanoreceptors may discriminate particles by size and regulate their passage into the duodenum [18]. Mucosal afferents may also be involved in the control of satiety, as their mechanosensitivity is enhanced by the satiety hormone, leptin, and reduced by the feeding hormone, ghrelin, both of which are released from gastric enteroendocrine cells that are in close proximity to the gastric mucosal afferent endings [19, 20]. In humans, ghrelin signalling to hypothalamic feeding centers is via the vagus [21]. P2X2 purine receptor immunoreactivity of intraganglionic laminar endings in the mouse gastrointestinal tract. Vagal afferent innervation of the proximal gastrointestinal tract mucosa: Chemoreceptor and mechano- receptor architecture. Vagal sensors in the rat duodenal mucosa: distribution and structure as revealed by in vivo DiI tracing. Vagal afferent innervation of the rat Fundic stomach: morphological characterization of the gastric tension receptor. Reprinted with permission from John Wiley and Sons Separate villus and crypt afferents innervate the mucosa of the small intestine [13]. Villus afferents have axons that project toward the villus tip, where they branch extensively. The branches have irregular flat expansions that tend to be close to the internal surface of the villus epithelium. Each villus afferent fiber typically innervates a cluster of two or more neighboring villi. The crypt afferents form subepithelial rings of varicose processes below the 3 The Enteric Nervous System and Gastrointestinal Innervation: Integrated. Assessment of single fibers filled by anterograde transport indicates that the villus and crypt afferents are independent endings of different vagal sensory neurons [13].