Pichia kudriavzevii as feed additive in Nile tilapia (Oreochromis niloticus) diet.

Yeasts are unicellular eukaryotic microorganisms extensively employed in various applications, notably as an alternative source of protein in feeds, owing to their nutritional benefits. Despite their potential, marine and mangrove yeast species used in the aquaculture industry have received little attention in the Philippines. Pichia kudriavzevii (A2B R1 ISO 3), sourced from bark samples, was selected and mass-produced due to its high protein content and amino acid profile. The dried biomass of P. kudriavzevii was incorporated into the diets of Nile tilapia (Oreochromis niloticus) juveniles at varying inclusion levels (0, 1, 2, and 4 g/kg diet) and its effect on their growth performance, body composition, and liver and intestinal morphology was assessed after 40 days of feeding. The groups that received P. kudriavzevii at a concentration of 2 g/kg diet exhibited higher final body weight, percent weight gain, and specific growth rate in comparison to the other treatment groups. Whole body proximate composition did not vary among the dietary groups. Intestinal and liver histopathology also indicated no abnormalities. These findings suggest the potential of ascomycetous P. kudriavzevii as a beneficial feed additive in Nile tilapia diets, warranting further investigation into its long-term effects and broader applications in fish culture.

Growth and fatty acid profiles of Halophytophthora vesicula and Salispina spinosa from Philippine mangrove leaves.

Studies on marine-sourced fatty acids have gathered significant interest recently as an important component of aquaculture feeds and of biofuel production. Of the organisms capable of producing fatty acids, marine oomycetes are promising model organisms. One group of marine oomycetes are the Halophytophthora spp. which is known to have an important role in leaf decomposition, thereby changing the plant debris into exudates which are usable to consumers in the mangrove ecosystems. This study reports the three mangrove oomycetes isolated from Philippine mangrove forests, identified herein as Halophytophthora vesicula AK1YB2 (Aklan), H. vesicula PQ1YB3 (Quezon) and Salispina spinosa ST1YB3 (Davao del Norte). These isolates were subjected to growth analyses using varying incubation parameters (salinity level and pH), and for fatty acid production. Results revealed the presence of different fatty acids such as Arachidonic acid, Linoleic acid and Vaccenic acid when grown on V8S and PYGS media. This study is the first observation of fatty acids from S. spinosa and H. vesicula from the Philippines. SIGNIFICANCE AND IMPACT OF THE STUDY: Tropical Philippines straddling west of the Pacific Ocean and East of South China Sea is rich in marine and estuarine oomycetes. These micro-organisms, hitherto poorly known and unstudied in the country, play an important role in the nutritive cycle of the mangrove ecosystem. Due to the increasing demand for an alternative source of fatty acids, species of Oomycetes isolated from select mangrove forests in Luzon, Visayas and Mindanao were analysed for their fatty acid contents. Prospects for industrially-important fatty acids make these Oomycetes all-important to study in applied microbiology in the Philippine setting where these structurally simple micro-organisms abound.

Revisiting Salisapiliaceae.

Of the diverse lineages of the Phylum Oomycota, saprotrophic oomycetes from the salt marsh and mangrove habitats are still understudied, despite their ecological importance. Salisapiliaceae, a monophyletic and monogeneric taxon of the marine and estuarine oomycetes, was introduced to accommodate species with a protruding hyaline apical plug, small hyphal diameter and lack of vesicle formation during zoospore release. At the time of description of Salisapilia, only few species of Halophytophthora, an ecologically similar, phylogenetically heterogeneous genus from which Salisapilia was segregated, were included. In this study, a revision of the genus Salisapilia is presented, and five new combinations (S. bahamensis, S. elongata, S. epistomia, S. masteri, and S. mycoparasitica) and one new species (S. coffeyi) are proposed. Further, the species description of S. nakagirii is emended for some exceptional morphological and developmental characteristics. A key to the genus Salisapilia is provided and its generic circumscription and character evolution in cultivable Peronosporales are discussed.

The extent that certain dairy farmer attitudes and behaviors are associated with farm business profitability.

The way in which farm managers' attitudes, personality, behavior, values, and sociodemographic characteristics influence farm business performance is, at best, only partially understood. The study reported here expands on this understanding by analyzing the attitudes and personal attributes of 80 dairy farmers in Great Britain in relation to the profitability over 3 yr of their farm businesses. Business goals, temperament, purchasing behavior, and having a growth mindset toward the business were found to be associated with profitability. A linear regression model consisting of 5 variables related to the above was presented that predicts 34% of the observed variation in profitability. Each of these variables were questions related to the participants' personal attitudes or beliefs. Other assessed variables, such as specific husbandry behaviors or practices, or management practices and sociodemographic characteristics, did not warrant inclusion in the final model. These results uniquely contribute to understanding how the attitudes, personality, behaviors, and attributes of dairy farmers are associated with, and thus likely to influence, the profitability of their farm businesses.

The political economy of bovine tuberculosis in Great Britain.

A brief history of bovine tuberculosis (bTB) and its control in Great Britain (GB) is presented. Numerous diverse policies to control the disease in humans, cattle and wildlife have been pursued over the last 100 years and many millions of pounds have been spent. After notable success in reducing the incidence and prevalence of bTB in cattle in GB from the 1950s to the mid-1980s, the geographical spread of the disease and the number of cattle slaughtered have increased continually since that time, with a high point of bTB incidence in 2008. This increase appeared to coincide with changing policy regarding the control of the disease in badgers, with a more humane approach adopted and with strengthened protection for badgers through legislation. Indeed, there has been much controversy in the debate on the role of badgers in disease transmission to cattle and the need for their control as vectors of the disease. The issue has attracted the attention of the media and there have been various commissioned research projects, trials and public consultations. The findings of two social science investigations presented as examples showed that citizens generally believed that bTB in cattle is an important issue that needs to be tackled, but objected to badgers being killed, whilst cattle farmers were willing to pay around £17/animal/year for a bTB cattle vaccine. It is noted that successes regarding the control of bTB in other countries have combined both cattle and wildlife controls and involved industry working in close partnership with government.

L'auteur retrace brièvement l'histoire de la tuberculose bovine et de la lutte contre cette maladie en Grande-Bretagne. Diverses mesures sanitaires ont été appliquées au cours des cent dernières années afin de maîtriser la maladie chez l'homme, chez les bovins et dans la faune sauvage, pour une dépense totale de plusieurs millions de livres. Après la chute remarquable de l'incidence et de la prévalence de la tuberculose bovine en Grande-Bretagne enregistrée depuis les années 50, la situation s'est inversée au milieu des années 80 et tant la distribution géographique de la maladie que le nombre de bovins abattus n'ont cessé de croître depuis cette date, l'année 2008 marquant le pic de l'incidence de la tuberculose bovine. Il est désormais établi que cette hausse a coïncidé avec l'évolution des politiques de lutte contre la tuberculose chez les blaireaux, à la faveur d'une approche plus respectueuse du bien-être animal qui s'est traduite par une protection renforcée des blaireaux dans la législation. En effet, le rôle des blaireaux dans la transmission de la tuberculose aux bovins et l'impératif de lutter contre les blaireaux en tant que vecteurs ont fait l'objet de très fortes controverses. Cette question a attiré l'attention des médias et il y a eu de nombreux projets de recherche commandités sur le sujet, d'expériences et de consultations publiques. D'après deux enquêtes sociologiques citées par l'auteur, les citoyens étaient généralement convaincus de l'importance de la tuberculose chez les bovins et de la nécessité de s'y attaquer mais ils s'opposaient aux mesures d'abattage des blaireaux, tandis que les éleveurs de bovins étaient disposés à payer environ 17 livres par bovin et par année pour pouvoir vacciner leurs bovins contre la tuberculose bovine. L'auteur fait observer que les succès enregistrés dans d'autres pays dans la lutte contre la tuberculose bovine sont liés à l'application combinée de mesures de contrôle chez les bovins et dans la faune sauvage et à une étroite collaboration entre les éleveurs et le gouvernement.

El autor repasa sucintamente la historia de la tuberculosis bovina y de su control en Gran Bretaña. En los últimos 100 años se han aplicado numerosas y variadas políticas y se han invertido muchos millones de libras para combatir la enfermedad en el ser humano, el ganado vacuno y la fauna silvestre. Entre mediados del decenio de 1950 y mediados del de 1980 se trabajó con notable éxito para reducir la incidencia y prevalencia de la enfermedad en el ganado vacuno británico. Pero a partir de ahí hubo una progresión constante en la propagación geográfica de la enfermedad y en el número de cabezas de ganado sacrificadas, con un máximo de incidencia registrado en 2008. Tal incremento parece coincidir con una inflexión de la política aplicada para luchar contra la enfermedad en los tejones, con la adopción de métodos más clementes y de medidas legislativas que instauraban un mayor nivel de protección de los tejones. Ha habido en efecto una gran controversia acerca del papel de los tejones en los procesos de transmisión de la enfermedad al ganado vacuno y la necesidad de controlar a esos animales como vectores de la infección. El tema ha suscitado gran atención mediática y ha sido objeto de una serie de proyectos de investigación, experimentos y consultas públicas. Según demuestran las conclusiones de dos investigaciones de ciencias sociales presentadas como ejemplo, en general los ciudadanos pensaban que la tuberculosis bovina en el ganado era un problema importante al que había que dar respuesta, pero se oponían al sacrificio de los tejones, a la vez que los ganaderos estaban dispuestos a pagar alrededor de 17 libras/animal/año por la vacunación antituberculosa de sus rebaños vacunos. El autor señala que los éxitos obtenidos en otros países a la hora de combatir la tuberculosis bovina pasan por instaurar controles a la vez en el ganado y en la fauna silvestre y por lograr que la industria trabaje en estrecha asociación con las instancias públicas.

Investigating the value dairy farmers place on a reduction of lameness in their herds using a willingness to pay approach.

A survey was conducted to elicit dairy farmers' willingness to pay (WTP) to reduce the prevalence of lameness in their herds. A choice experiment questionnaire was administered using face-to-face interviews of 163 farmers in England and Wales. Whole herd lameness assessments by trained researchers recorded a mean lameness prevalence of nearly 24% which was substantially higher than that estimated by farmers. Farmers' responses to a series of attitudinal questions showed that they strongly agreed that cows can suffer a lot of pain from lameness and believed that they could reduce lameness in their herds. Farmers' mean WTP to avoid lameness amounted to UK£411 per lame cow but with considerable variation across the sample. Median WTP of UK£249 per lame cow was considered a better measure of central tendency for the sample. In addition, the survey found that farmers had a substantial WTP to avoid the inconvenience associated with lameness control (a median value of UK£97 per lame cow) but that they were generally prepared to incur greater inconvenience if it reduced lameness. The study findings suggest that farmers need a better understanding of the scale and costs of lameness in their herds and the benefits of control. To encourage action, farmers need to be convinced that lameness control measures perceived as inconvenient will be cost effective.

Modelling of control options for an outbreak of Mycoplasma gallisepticum in egg production: a decision support tool.

Mycoplasma gallisepticum (MG) is a bacterium that causes respiratory disease in chickens, leading to reduced egg production. A dynamic simulation model was developed that can be used to assess the costs and benefits of control using antimicrobials or vaccination in caged or free range systems. The intended users are veterinarians and egg producers. A user interface is provided for input of flock specific parameters. The economic consequence of an MG outbreak is expressed as a reduction in expected egg output. The model predicts that either vaccination or microbial treatment can approximately halve potential losses from MG in some circumstances. Sensitivity analysis is used to test assumptions about infection rate and timing of an outbreak. Feedback from veterinarians points to the value of the model as a discussion tool with producers.

Assessing fibromyalgia-related fatigue: content validity and psychometric performance of the Fatigue Visual Analog Scale in adult patients with fibromyalgia.

OBJECTIVES: To document 1) the content validity and 2) measure improvements in fatigue, using the Fatigue Visual Analogue Scale (VAS) assessment tool in patients with fibromyalgia. METHODS: The relevance and comprehensiveness of the Fatigue VAS were tested through a qualitative analysis of 20 subjects' verbatim transcripts from semi-structured qualitative interviews. Data from two randomised, controller trials in fibromyalgia (n=1121) were used to conduct correlation analyses with the Fatigue and Tiredness items from the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form-36 Vitality scale. Known-groups and cross classification analyses were conducted to demonstrate the ability to measure improvement in fatigue using the Fatigue VAS. RESULTS: All subjects spontaneously reported that fatigue was an important symptom to capture in fibromyalgia. The Fatigue VAS was well understood by most subjects (n=18/20). High correlations (Pearson r>0.75) and good agreement (k>0.66) were found between the Fatigue VAS and the FIQ tiredness items no. 16 and 17 and SF-36™ Vitality scale. In both clinical trials there was a substantial separation of approximately 20 points on the mean change in the Fatigue VAS score between responders (>30% improvement in pain VAS) and non-responders. CONCLUSIONS: Previous studies have confirmed that fatigue is a major component of the fibromyalgia experience. This current study reports that fibromyalgia patients spontaneously rated fatigue as a highly significant feature of their illness, and supports the use of the Fatigue VAS as a valid questionnaire in fibromyalgia clinical trials.

Farm costs associated with premovement testing for bovine tuberculosis.

Sixty cattle farmers in England were questioned about the costs associated with premovement testing for bovine tuberculosis (TB). On average, the farmers had premovement tested 2.45 times in the previous 12 months, but the majority had tested only once. An average of 28.6 animals were tested on each occasion, but there were wide variations. The average farm labour costs were 4.00 pounds per animal tested, veterinary costs were 4.33 pounds and other costs were 0.51 pounds, giving a total cost of 8.84 pounds, but there were wide variations between farms, and many incurred costs of more than 20 pounds per animal. A majority of the farmers also cited disruption to the farm business or missed market opportunities as costs, but few could estimate their financial cost. Most of the farmers thought that premovement testing was a cost burden on their business, and over half thought it was not an effective policy to control bovine TB.

A six-month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia.

OBJECTIVE: A subset of fibromyalgia (FM) patients have a dysfunctional hypothalamic-pituitary-insulin-like growth factor 1 (IGF-1) axis, as evidenced by low serum levels of IGF-1 and a reduced growth hormone (GH) response to physiologic stimuli. There is evidence that pyridostigmine (PYD) improves the acute response of GH to exercise in FM patients. The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on FM symptoms. METHODS: FM patients were randomized to 1 of the following 4 groups: PYD plus exercise, PYD plus diet recall but no exercise, placebo plus exercise, and placebo plus diet recall but no exercise. The primary outcome measures were the visual analog scale (VAS) score for pain, tender point count, and total myalgic score. Secondary outcome measures were the total score on the Fibromyalgia Impact Questionnaire (FIQ) and FIQ VAS scores for individual symptoms (fatigue, poor sleep, stiffness, and anxiety), as well as quality of life (QOL) and physical fitness (lower body strength/endurance, upper and lower body flexibility, balance, and time on the treadmill). RESULTS: A total of 165 FM patients completed baseline measurements; 154 (93.3%) completed the study. The combination of PYD and exercise did not improve pain scores. PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups. Compared with the nonexercise groups, the 2 exercise groups demonstrated improvement in fatigue and fitness. PYD was generally well tolerated. CONCLUSION: Neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most FM symptoms. However, PYD did improve anxiety and sleep, and exercise improved fatigue and fitness. We speculate that PYD may have improved vagal tone, thus benefiting sleep and anxiety; this notion warrants further study.

Costs to farmers of a tuberculosis breakdown.

An on-farm survey of 151 cattle farmers who had experienced a bovine tuberculosis (Mycobacterium bovis) breakdown on their farms was undertaken in 2003 to assess the costs associated with the breakdown. In 90 per cent of cases the cost was estimated to be less than 18,513 pounds sterling for dairy herds and less than 11,462 pounds sterling for beef herds, but with a range from 229 pounds sterling to 103,817 pounds sterling. The main cost was the slaughter of reactor cattle. For the majority of the farmers, the compensation payments seemed to meet most of the costs of their breakdowns, although a majority was still left with net losses.

Effects of dissolved carbon dioxide on the physiology and behavior of fish in artificial streams.

A new technology for treating waters contaminated with acid mine drainage involves the dissolution of limestone particles using carbon dioxide at pressures above ambient. Because of the fish health risks associated with episodes of high carbon dioxide levels in treated waters, we subjected three species of fish, brook trout (Salvelinus fontinalis), slimy sculpin (Cottus cognatus), and blacknose dace (Rhinichthys atratulus), to 24 h exposures of elevated dissolved carbon dioxide (CO2) at three levels, ranging from 1.0 (low) to 6.3 (high)%, under laboratory conditions. We measured blood physiological variables as well as behavior, including feeding responses, before, during, and after exposure. Physiological responses differed by species, but all species had elevated hematocrits after 1 h of exposure. Brook trout hematocritis were higher at medium and high levels of CO2 than in a control group (0.0% CO2) after 24 h of exposure. Slimy sculpin hematocrits were higher in medium- and high-level exposure groups than in controls after 1 h, but not after 24 h, of exposure. Blacknose dace hematocrits were higher in all three exposure groups than in controls after 1 h but only in medium-level exposure groups after 24 h. Brook trout plasma glucose was significantly higher in medium- and high-level exposure groups after 1 h, and in the high-level group after 24 h, than in controls. Slimy sculpin plasma glucose was not significantly different in elevated CO2 exposure groups from that of controls throughout exposure. Branchial ventilation was significantly greater in all species at elevated CO2 during exposure, indicating stress; however, no difference was observed between treatment and control groups of blacknose dace after 24 h, indicating acclimation. Pectoral fin beats and cough rates were not consistently related to CO2 exposure throughout the study. Brook trout had the longest lasting reaction to stress at lower levels of CO2 among the three species tested. Many of the 11 observed behavioral variables, related to swimming, feeding, social, and illness factors, were affected by elevations of dissolved CO2. Two to seven behavioral variables (18-64% of those measured) were affected by treatment level of dissolved CO2 with a trend by species for the number of variables affected: brook trout > blacknose dace > slimy sculpin. However, behavioral sensitivity to treatment level was greatest in blacknose dace. Recovery to pre-treatment activity rates for most behavior patterns (including feeding) was observed 24 h after cessation of exposure in all three species. Recovery was independent of treatment level, was most rapid in blacknose dace, and was slowest in brook trout. Overall, slimy sculpin was least affected behaviorally by elevated CO2. Although all three species showed stress response and changes in behavior at moderate levels of CO2 (> or = 2%), brook trout and blacknose dace showed evidence of ability to avoid harmful CO2 levels by swimming out of affected waters, whereas the slimy sculpin showed minimal behavioral changes despite remaining in place during exposure. Thus, predation risk and other sources of mortality seem minimal in the event of technological malfunction at a stream treatment site involving the use of CO2 under pressure.

A human gene coding for a membrane-associated nucleic acid-binding protein.

Studies to clone a cell-surface DNA-binding protein involved in the binding and internalization of extracellular DNA have led to the isolation of a gene for a membrane-associated nucleic acid-binding protein (MNAB). The full-length cDNA is 4.3 kilobases with an open reading frame of 3576 base pairs encoding a protein of approximately 130 kDa (GenBank accession numbers and ). The MNAB gene is on human chromosome 9 with wide expression in normal tissues and tumor cells. A C3HC4 RING finger and a CCCH zinc finger have been identified in the amino-terminal half of the protein. MNAB bound DNA (K(D) approximately 4 nm) and mutagenesis of a single conserved amino acid in the zinc finger reduced DNA binding by 50%. A potential transmembrane domain exists near the carboxyl terminus. Antibodies against the amino-terminal half of the protein immunoprecipitated a protein of molecular mass approximately 150 kDa and reacted with cell surfaces. The MNAB protein is membrane-associated and primarily localized to the perinuclear space, probably to the endoplasmic reticulum or trans-Golgi network. Characterization of the MNAB protein as a cell-surface DNA-binding protein, critical in binding and internalization of extracellular DNA, awaits confirmation of its localization to cell surfaces.

Quantification of DNA binding to cell-surfaces by flow cytometry.

DNA binding to cell-surfaces has been documented in several studies. The interaction of DNA with cells has been shown to have therapeutic potential as a non-viral form of gene delivery and DNA vaccination. Recently, bacterial DNA binding and internalization has been demonstrated in some cells to trigger secretion of cytokines and cell activation. Previous studies to quantify DNA binding to cells have used radiolabeled DNA. Here we report a non-radioactive assay for quantification of cell-surface DNA binding based on the isoparametric analysis of flow cytometric data as described by Chatelier et al., Embo J., 5 (1986) 1181. This assay has the advantage over previously used procedures in not employing radioactive material and being able to discriminate viable from non-viable cells that bind DNA. With the importance of understanding the interaction of DNA with cells, this assay may have application for the identification and characterization of reagents designed to either enhance or inhibit DNA binding to cells.

Efficacy of tramadol in treatment of pain in fibromyalgia.

An outpatient, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy and safety of tramadol in the treatment of the pain of fibromyalgia syndrome. One hundred patients with fibromyalgia syndrome, (1990 American College of Rheumatology criteria), were enrolled into an open-label phase and treated with tramadol 50-400 mg/day. Patients who tolerated tramadol and perceived benefit were randomized to treatment with tramadol or placebo in the double-blind phase. The primary efficacy outcome measurement was the time (days) to exit from the double-blind phase because of inadequate pain relief, which was reported as the cumulative probability of discontinuing treatment because of inadequate pain relief. One hundred patients entered the open-label phase; 69% tolerated and achieved benefit with tramadol. These patients were then randomized to continue tramadol (n = 35) or convert to a placebo (n = 34) during a 6-week, double-blind treatment period. The Kaplan-Meier estimate of cumulative probability of discontinuing the double blind period because of inadequate pain relief was significantly lower in the tramadol group compared with the placebo group (p = 0.001). Twenty (57.1%) patients in the tramadol group successfully completed the entire double-blind phase compared with nine (27%) in the placebo group (p = .015). These results support the efficacy of tramadol over a period of 6 weeks in a double blind study for the treatment of the pain of fibromyalgia in a group of patients who had been determined to tolerate it and perceive a benefit.

Musculoskeletal pain and fatigue are associated with chronic hepatitis C: a report of 239 hepatology clinic patients.

OBJECTIVE: The aim of this study was to identify the frequency of fatigue and musculoskeletal pain in hepatitis C compared with other liver diseases. METHODS: Hepatology outpatients were evaluated by questionnaire for musculoskeletal pain and fatigue. Charts were reviewed for diagnoses, aminotransferases, histology, treatment, and presence of hepatitis C by second generation ELISA and/or polymerase chain reaction. The frequency of symptoms in patients with and without hepatitis C were compared. RESULTS: In 239 patients (mean age 46.7 +/- 11.6 yr; 52% male) musculoskeletal pain was present in 70% for 6.7 +/- 8.3 yr and fatigue in 56% for 3.3 +/- 5.1 yr. Backache was the most common complaint (54%), followed by morning stiffness (45%), arthralgia (42%), myalgia (38%), neck pain (33%), pain "all over" (21%), and subjective joint swelling (20%). Diffuse body pain was present in 23% on a pain diagram and was strongly associated with fatigue. There was a significant association between hepatitis C positivity and the presence of musculoskeletal pain (81% of HCV-positive compared with 56% of HCV-negative patients, respectively; p = 0.0001), and fatigue (67% compared with 44%; p = 0.001). Musculoskeletal pain was more frequent among patients with isolated hepatitis C infection than among patients with isolated hepatitis B or alcoholic liver disease (91%, 59%, and 48%, respectively; p = 0.004). Similarly, fatigue was more frequent among patients with isolated hepatitis C than among those with isolated alcoholic liver disease or hepatitis B (66%, 30%, and 29%, respectively; p = 0.004). There was no relationship between musculoskeletal complaints and possible route of acquiring hepatitis C, levels of aminotransferases, liver disease severity on biopsy, or interferon treatment. CONCLUSIONS: Musculoskeletal pain and fatigue are frequent in hepatology clinic attendees, particularly those with hepatitis C and are unrelated to severity of liver disease, route of infection, or interferon therapy.

Emerging concepts in the neurobiology of chronic pain: evidence of abnormal sensory processing in fibromyalgia.

Chronic pain often differs from acute pain. The correlation between tissue pathology and the perceived severity of the chronic pain experience is poor or even absent. Furthermore, the sharp spatial localization of acute pain is not a feature of chronic pain; chronic pain is more diffuse and often spreads to areas beyond the original site. Of importance, chronic pain seldom responds to the therapeutic measures that are successful in treating acute pain. Physicians who are unaware of these differences may label the patient with chronic pain as being neurotic or even a malingerer. During the past decade, an exponential growth has occurred in the scientific underpinnings of chronic pain states. In particular, the concept of nonnociceptive pain has been refined at a physiologic, structural, and molecular level. This review focuses on this new body of knowledge, with particular reference to the chronic pain state termed "fibromyalgia."