Search

Intestinal neoplasms and preneoplastic lesions are common in zebrafish research facilities. Previous studies have demonstrated that these neoplasms are caused by a transmissible agent, and two candidate agents have been implicated: a Mycoplasma sp. related to Mycoplasma penetrans and the intestinal parasitic nematode, Pseudocapillaria tomentosa, and both agents are common in zebrafish facilities. To elucidate the role of these two agents in the occurrence and severity of neoplasia and other intestinal lesions, we conducted two experimental inoculation studies. Exposed fish were examined at various time points over an 8-month period for intestinal histopathologic changes and the burden of Mycoplasma and nematodes. Fish exposed to Mycoplasma sp. isolated from zebrafish were associated with preneoplastic lesions. Fish exposed to the nematode alone or with the Mycoplasma isolate developed severe lesions and neoplasms. Both inflammation and neoplasm scores were associated with an increase in Mycoplasma burden. These results support the conclusions that P. tomentosa is a strong promoter of intestinal neoplasms in zebrafish and that Mycoplasma alone can also cause intestinal lesions and accelerate cancer development in the context of nematode infection.

Rodney Phillips Dales was born in Hornchurch, Essex on 15 January 1927. His father Sidney Phillips Dales was a Chartered Architect, his mother Muriel Emily (née Tattersall) kept the family home in the Squirrel’s Heath district, and frequently worked in her husband’s practice. Rodney and his brother Gordon (b. 1922) were raised in a strict Methodist family. They led a modest life, but one full of interest and diversion. Frequent trips to the seaside, and visits to buildings and artist friends of his father, helped shape Rodney’s interests and future career. He became fascinated by the diversity of the natural world and the wonderful architecture he encountered on his frequent bike rides into the Essex countryside.

Supplemental Digital Content is Available in the Text. A 6-day ambulatory continuous peripheral nerve block reduces phantom limb pain and pain-induced physical and emotional dysfunction for at least 4 weeks after treatment., Phantom limb pain is thought to be sustained by reentrant neural pathways, which provoke dysfunctional reorganization in the somatosensory cortex. We hypothesized that disrupting reentrant pathways with a 6-day-long continuous peripheral nerve block reduces phantom pain 4 weeks after treatment. We enrolled patients who had an upper- or lower-limb amputation and established phantom pain. Each was randomized to receive a 6-day perineural infusion of either ropivacaine or normal saline. The primary outcome was the average phantom pain severity as measured with a Numeric Rating Scale (0-10) at 4 weeks, after which an optional crossover treatment was offered within the following 0 to 12 weeks. Pretreatment pain scores were similar in both groups, with a median (interquartile range) of 5.0 (4.0, 7.0) for each. After 4 weeks, average phantom limb pain intensity was a mean (SD) of 3.0 (2.9) in patients given local anesthetic vs 4.5 (2.6) in those given placebo (difference [95% confidence interval] 1.3 [0.4, 2.2], P = 0.003). Patients given local anesthetic had improved global impression of change and less pain-induced physical and emotional dysfunction, but did not differ on depression scores. For subjects who received only the first infusion (no self-selected crossover), the median decrease in phantom limb pain at 6 months for treated subjects was 3.0 (0, 5.0) vs 1.5 (0, 5.0) for the placebo group; there seemed to be little residual benefit at 12 months. We conclude that a 6-day continuous peripheral nerve block reduces phantom limb pain as well as physical and emotional dysfunction for at least 1 month.

Detecting the presence of important parasites within a host and its environment is critical to understanding the dynamics that influence a pathogens ability to persist, while accurate detection is also essential for implementation of effective control strategies. Pseudoloma neurophilia is the most common pathogen reported in zebrafish (Danio rerio) research facilities. The only assays currently available for P. neurophilia, are through lethal sampling, often requiring euthanasia of the entire population for accurate estimates of prevalence in small populations. We present a non-lethal screening method to detect Pseudoloma neurophilia in tank water based on detection of environmental DNA (eDNA) from this microsporidum, using a previously developed qPCR assay that was adapted to the digital PCR (dPCR) platform. Using the generated dPCR data, a multi-state occupancy model was also implemented to predict the probability of detection in tank water under different flow regimes and pathogen prevalence. The occupancy model revealed that samples collected in static conditions were more informative than samples collected from flow-through conditions, with a probability of detection at 80% and 47%, respectively. There was also a positive correlation with the prevalence of infection in water and prevalence in fish based on qPCR.

Specific pathogen-free (SPF) animals are bred and managed to exclude pathogens associated with significant morbidity or mortality that may secondarily pose a risk to public health, food safety and food security, and research replicability. Generating and maintaining SPF animals requires detailed biosecurity planning for control of housing, environmental, and husbandry factors and a history of regimented pathogen testing. Successful programs involve comprehensive risk analysis and exclusion protocols that are rooted in a thorough understanding of pathogen lifecycle and modes of transmission. In this manuscript we review the current state of SPF in domestic agriculture (pigs and poultry), aquaculture (salmonids and shrimp), and small laboratory mammals. As the use of laboratory fish, especially zebrafish (Danio rerio), as models of human disease is expanding exponentially, it is prudent to define standards for SPF in this field. We use the guiding principles from other SPF industries and evaluate zebrafish pathogens against criteria to be on an SPF list, to propose recommendations for establishing and maintaining SPF laboratory zebrafish.

Background Pain trajectories have been described in numerous surgical settings where preoperative characteristics have been used to predict trajectory membership. Suboptimal pain intensity trajectories have been linked to poor longitudinal outcomes. However, numerous biopsychosocial modulators of postoperative pain may also have distinct longitudinal trajectories that may inform additional targets to improve postoperative recovery. Methods Patients undergoing total joint arthroplasty, thoracic surgery, spine surgery, major abdominal surgery, or mastectomy completed Patient Reported Outcome Measurement Information System (PROMIS) measures and additional scales preoperatively and at 1 week, 2 weeks, 1 month, 3 months, and 6 months postoperatively. A k-means clustering for longitudinal data was utilized to explore and describe distinct pain impact (PROMIS Pain Interference and Physical Function) trajectories and associated changes in additional biopsychosocial measures. Follow-up analyses examined participant demographics and clinical characteristics associated with trajectory memberships. Results Three postoperative biopsychosocial symptom clusters were identified across all patients (n = 402): low (35%), average (47%), and high (18%) performance cluster trajectories. Participants undergoing total knee arthroplasty (TKA), spinal surgery, reporting presurgical opioid use, and higher pain catastrophizing scale scores were found to be associated with the low performance trajectory. Patients within the low performance trajectory, while demonstrating small improvements by 6 months, remained mild to moderately impaired in both pain impact and physical health outcomes. Alternatively, participants in the average performance trajectory demonstrated improvement in pain impact to population norms compared to baseline and demonstrated continued improvement across physical and psychological outcomes. Patients within the high performance cluster started within population norms across all measures at baseline and returned to baseline or exceeded baseline values by 6 months postoperatively. Self-reported opioid utilization was significantly higher in the low performance cluster across all time points. While a larger proportion of average performance patients reported opioid utilization during the first postoperative month compared to the high performance cluster, no differences were detected at 6 months postoperatively between these 2 clusters. Conclusions These pain impact trajectories build upon previous unidimensional pain intensity trajectories and suggest that additional distinct biopsychosocial measures may have unique trajectories related to cluster assignment. Additionally, these findings highlight the importance of continued pain impact surveillance through the perioperative recovery period to detect patients at risk of experiencing a poor trajectory and subsequently poor longitudinal health outcomes.

BACKGROUND We recently reported that a 6-day continuous peripheral nerve block reduced established postamputation phantom pain 3 weeks after treatment ended. However, the immediate effects of perineural infusion (secondary outcomes) have yet to be reported. METHODS Participants from 5 enrolling academic centers with an upper or lower limb amputation and established phantom pain received a single-injection ropivacaine peripheral nerve block(s) and perineural catheter insertion(s). They were subsequently randomized to receive a 6-day ambulatory perineural infusion of either ropivacaine 0.5% or normal saline in a double-masked fashion. Participants were contacted by telephone 1, 7, 14, 21, and 28 days after the infusion started, with pain measured using the Numeric Rating Scale. Treatment effects were assessed using the Wilcoxon rank-sum test at each time point. Adjusting for 4 time points (days 1, 7, 14, and 21), P < .0125 was deemed statistically significant. Significance at 28 days was reported using methods from the original, previously published article. RESULTS Pretreatment average phantom and residual pain scores were balanced between the groups. The day after infusion initiation (day 1), average phantom, and residual limb pain intensity was lower in patients receiving local anesthetic (n = 71) versus placebo (n = 73): median [quartiles] of 0 [0-2.5] vs 3.3 [0-5.0], median difference (98.75% confidence interval [CI]) of -1.0 (-3.0 to 0) for phantom pain (P = .001) and 0 [0-0] vs 0 [0-4.3], and median difference 0.0 (-2.0 to 0.0) for residual limb pain (P < .001). Pain's interference with physical and emotional functioning as measured with the interference domain of the Brief Pain Inventory improved during the infusion on day 1 for patients receiving local anesthetic versus placebo: 0 [0-10] vs 10 [0-40], median difference (98.75% CI) of 0.0 (-16.0 to 0.0), P = .002. Following infusion discontinuation (day 6), a few differences were found between the active and placebo treatment groups between days 7 and 21. In general, sample medians for average phantom and residual limb pain scores gradually increased after catheter removal for both treatments, but to a greater degree in the control group until day 28, at which time the differences between the groups returned to statistical significance. CONCLUSIONS This secondary analysis suggests that a continuous peripheral nerve block decreases phantom and residual limb pain during the infusion, although few improvements were again detected until day 28, 3 weeks following catheter removal.

Crassiphialinae Sudarikov, 1960 is a large subfamily of the Diplostomidae Poirier, 1886 with a complex taxonomic history. It includes a diversity of species parasitic in the intestines of avian and mammalian definitive hosts worldwide. Posthodiplostomum Dubois, 1936 is a large and broadly distributed crassiphialine genus notorious for its association with diseases in their fish second intermediate hosts. In this study, we generated partial 28S rDNA and cytochrome c oxidase subunit 1 (cox1) mtDNA gene sequences of digeneans beloning to seven crassiphialine genera. The 28S sequences were used to study the interrelationships among crassiphialines and their placement among other major diplostomoidean lineages. Our molecular phylogenetic analysis and review of morphology does not support subfamilies currently recognized in the Diplostomidae; therefore, we abandon the current subfamily system of the Diplostomidae. Molecular phylogenetic analyses suggest the synonymy of Posthodiplostomum, Ornithodiplostomum Dubois, 1936 and Mesoophorodiplostomum Dubois, 1936 ; morphological study of our well-fixed adult specimens and review of literature revealed lack of consistent differences among the three genera. Thus, we synonymize Ornithodiplostomum and Mesoophorodiplostomum with Posthodiplostomum. Our phylogenetic analyses suggest an Old World origin of Posthodiplostomum followed by multiple dispersal events among biogeographic realms. Furthermore, our analyses indicate that the ancestors of these digeneans likely parasitized ardeid definitive hosts. Four new species of Posthodiplostomum collected from birds in the New World as well as one new species of Posthodiplostomoides Williams, 1969 from Uganda are described.

Pseudocapillaria tomentosa is an important pathogen in zebrafish facilities. We investigated heat, ultraviolet (UV) light, chlorine, iodine, and dessciation for killing the parasite's eggs...

Surgical care episodes place opioid-naïve patients at risk for transitioning to new persistent postoperative opioid use. With one of the central principles being the application of multimodal pain interventions to reduce the reliance on opioid-based medications, enhanced recovery pathways provide a framework that decreases perioperative opioid use. The fourth Perioperative Quality Initiative brought together a group of international experts representing anesthesiology, surgery, and nursing with the objective of providing consensus recommendations on this important topic. Fourth Perioperative Quality Initiative was a consensus-building conference designed around a modified Delphi process in which the group alternately convened for plenary discussion sessions in between small group discussions. The process included several iterative steps including a literature review of the topics, building consensus around the important questions related to the topic, and sequential steps of content building and refinement until agreement was achieved and a consensus document was produced. During the fourth Perioperative Quality Initiative conference and thereafter as a writing group, reference applicability to the topic was discussed in any area where there was disagreement. For this manuscript, the questions answered included (1) What are the potential strategies for preventing persistent postoperative opioid use? (2) Is opioid-free anesthesia and analgesia feasible and appropriate for routine operations? and (3) Is opioid-free (intraoperative) anesthesia associated with equivalent or superior outcomes compared to an opioid minimization in the perioperative period? We will discuss the relevant literature for each questions, emphasize what we do not know, and prioritize the areas for future research.

Persistent postoperative opioid use is thought to contribute to the ongoing opioid epidemic in the United States. However, efforts to study and address the issue have been stymied by the lack of a standard definition, which has also hampered efforts to measure the incidence of and risk factors for persistent postoperative opioid use. The objective of this systematic review is to (1) determine a clinically relevant definition of persistent postoperative opioid use, and (2) characterize its incidence and risk factors for several common surgeries. Our approach leveraged a group of international experts from the Perioperative Quality Initiative-4, a consensus-building conference that included representation from anesthesiology, surgery, and nursing. A search of the medical literature yielded 46 articles addressing persistent postoperative opioid use in adults after arthroplasty, abdominopelvic surgery, spine surgery, thoracic surgery, mastectomy, and thoracic surgery. In opioid-naive patients, the overall incidence ranged from 2% to 6% based on moderate-level evidence. However, patients who use opioids preoperatively had an incidence of >30%. Preoperative opioid use, depression, factors associated with the diagnosis of substance use disorder, preoperative pain, and tobacco use were reported risk factors. In addition, while anxiety, sex, and psychotropic prescription are associated with persistent postoperative opioid use, these reports are based on lower level evidence. While few articles addressed the health policy or prescriber characteristics that influence persistent postoperative opioid use, efforts to modify prescriber behaviors and health system characteristics are likely to have success in reducing persistent postoperative opioid use.

ObjectiveRecent efforts to update the definitions and taxonomic structure of concepts related to pain have revealed opportunities to better quantify topics of existing pain research subject areas.MethodsHere, we apply basic natural language processing (NLP) analyses on a corpus of >200,000 abstracts published on PubMed under the medical subject heading (MeSH) of “pain” to quantify the topics, content, and themes on pain-related research dating back to the 1940s.ResultsThe most common stemmed terms included “pain” (601,122 occurrences), “patient” (508,064 occurrences), and “studi-” (208,839 occurrences). Contrarily, terms with the highest term frequency–inverse document frequency included “tmd” (6.21), “qol” (6.01), and “endometriosis” (5.94). Using the vector-embedded model of term definitions available via the “word2vec” technique, the most similar terms to “pain” included “discomfort,” “symptom,” and “pain-related.” For the term “acute,” the most similar terms in the word2vec vector space included “nonspecific,” “vaso-occlusive,” and “subacute”; for the term “chronic,” the most similar terms included “persistent,” “longstanding,” and “long-standing.” Topic modeling via Latent Dirichlet analysis identified peak coherence (0.49) at 40 topics. Network analysis of these topic models identified three topics that were outliers from the core cluster, two of which pertained to women’s health and obstetrics and were closely connected to one another, yet considered distant from the third outlier pertaining to age. A deep learning–based gated recurrent units abstract generation model successfully synthesized several unique abstracts with varying levels of believability, with special attention and some confusion at lower temperatures to the roles of placebo in randomized controlled trials.ConclusionsQuantitative NLP models of published abstracts pertaining to pain may point to trends and gaps within pain research communities.

The zebrafish is a widely used animal model in biomedical research. Despite this, pathogens continue to be common in laboratory zebrafish. It is important to determine and describe the pathophysiology of cryptic infections on zebrafish to elucidate the impacts on experimental endpoints. Body condition is a basic measurement used experimentally and in health monitoring of animals. We exposed three wild-type zebrafish strains: AB, WIK, and 5D to Pseudoloma neurophilia. After 8 weeks postexposure, we individually imaged and processed fish for histology. Morphometric analysis was performed on images and an index of body condition was calculated based on the ratio of length/width from the dorsal aspect. Histological sections from each fish were examined to establish sex, severity of infection, and tissue distribution. We observed a significant decrease in body condition in female fish that was not observed in males. In addition, we observed a negative correlation between the total gonadal area of P. neurophilia exposed females and unexposed controls. These results illustrate the sex-specific impacts of a common chronic pathogen on zebrafish health and a commonly used experimental endpoint, further supporting the establishment of rigorous health monitoring programs in laboratory zebrafish colonies that include screening for chronic infectious diseases.

Intestinal helminth parasites present major challenges to the welfare of humans and threaten the global food supply. While the discovery of anthelminthic drugs empowered our ability to offset these harms to society, the alarming rise of anthelminthic drug resistance mitigates contemporary efforts to treat and control intestinal helminthic infections. Fortunately, emerging research points to potential opportunities to combat anthelminthic drug resistance by harnessing the gut microbiome as a resource for discovering novel therapeutics and informing responsible drug administration. In this review, we highlight research that demonstrates this potential and provide rationale to support increased investment in efforts to uncover and translationally utilize knowledge about how the gut microbiome mediates intestinal helminthic infection and its outcomes.

ObjectivesThe National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) is a multidimensional screening system evaluating biopsychosocial factors affecting pain and functioning. Using a military sample, the current study 1) examined the structure and domains of the PROMIS, the Defense and Veterans Pain Rating Scale 2.0 (DVPRS), and the Pain Catastrophizing Scale (PCS) within a presurgical setting and 2) examined the relationship of these variables to pre- and postsurgical opioid use.MethodsThis cross-sectional study included 279 adult patients scheduled for surgery at the Walter Reed National Military Medical Center and a validation sample of 79 additional patients from the Naval Medical Center, San Diego. PROMIS, DVPRS, PCS, and opioid use data were collected before surgery. Exploratory factor analysis and confirmatory factor analysis identified the latent structure for the measures. A structural equation model (SEM) examined their relationship to pre- and postsurgical opioid use.ResultsTwo latent factors represented Psychosocial Functioning (PROMIS Depression, PROMIS Anxiety, and PROMIS Social Isolation) and Pain Impact (DVPRS, PROMIS Pain Interference, PROMIS Physical Functioning). The remaining PROMIS scales did not load onto a single factor. In the SEM, the two latent factors and PCS were significantly related to pre- and postsurgical opioid use.ConclusionsThis study highlights the utility and relative ease of using a convenient multidimensional assessment in presurgical settings. Using such an assessment can help provide targeted interventions for individuals who may be at greatest risk for negative postsurgical outcomes.

A laboratory zebrafish colony developed red masses, predominantly under the jaw, in a significant portion of the population. The masses were diagnosed histopathologically as thyroid follicular hyperplasia, adenoma, or carcinoma in accordance with published morphologic criteria. After switching to a higher iodine brand of salt used to maintain a low level of salinity within the water system and a small diet change, the thyroid lesions regressed dramatically. Within 5 months the masses were no longer grossly visible. At the population level, external evaluations and histopathological assessments of whole-body sections document a regression in the prevalence of thyroid neoplasia and hyperplasia to normal thyroid conformation by 11 months after salt change. These findings suggest that a wide range of proliferative thyroid lesions, including neoplasms, in zebrafish may be hormone-dependent, even following lesion development. In addition, these results suggest that zebrafish have an adaptive ability to absorb iodine from water and food, which should be considered in discussions to standardize diets and when describing environmental parameters in publications.

The crisis strategy of scapegoating has been part of the crisis and image restoration lexicon for more than four decades. And yet, the practice of scapegoating is a well-known unethical practice that simply deflects deserved blame from one party to a sacrificial other. This essay critiques the “Primary Crisis Response” strategy of scapegoating, conducting an historical and ethical critique of the crisis strategy, and concludes that scapegoating should be removed from the public relations crisis and image restoration lexicon.

Although robust theories of radio, television, cinema, journalism, and other areas of mass media already exist, the social media sphere has received relatively little original theorizing. Modeled after Berger and Calabrese’s (1975) seminal “axioms of human communication” article, this essay takes stock of the existing research on social media, and uses the same approach to theorizing about social media, advancing 7 axioms and 21 theorems, and exploring how the propositions chronicled can be used to build social media theory and improve public relations practice.

This study evaluated the hematological profile and condition factor (Kn) of tui chub Siphateles bicolor and fathead minnow Pimephales promelas and their associations with larvae of Contracaecum sp. infection of the heart. A total of 30 tui chub and 17 fathead minnow were collected from Upper Klamath Lake, Oregon, USA, measured, and weighed and blood was drawn for hematological analysis. Nematode larvae parasitized tui chub with a prevalence of 50% and mean intensity of 1.40, while 11.8% of fathead minnow were parasitized at a mean intensity of 1.0. Non-parasitized tui chub were significantly larger than the parasitized fish, indicating that small fish could be easily predated by the definitive host, a piscivorous bird. Although the relatively large worm occupied a large portion of the atrium, the presence of the larvae did not affect tui chub Kn, possibly associated with low parasite intensity and a harmonic co-evolution. Only parasitized fathead minnow showed significant differences in red blood cell measurements (greater cell width and larger nuclei) compared to non-parasitized fish. Lymphocytes were the most common white blood cells found in tui chub, followed by neutrophils, monocytes, and periodic acid-Schiff positive granular leukocytes; in fathead minnow lymphocytes were followed by heterophils, monocytes, neutrophils and eosinophils. This study is the first report of Kn and description of blood cells and hematological parameters in these fish species.

Highlights - The article builds on dialogic theory by introducing the metaphor of the Rhizome. - The article argues arboreal relationships are ineffective public relations tools. - The article argues a rhizomatous pedagogical and practice model extends the field. Abstract Communication shapes both reality and thought. Communication is also influenced by the metaphors and paradigms that individuals and groups adhere to. This essay describes an alternative, dialogic, metaphor of public relations as a rhizome, or non-linear model of knowledge, communication, and culture. The rhizome is described in contradistinction to the more common arboreal or tree metaphor found throughout Western culture, as a means of changing how students and professionals reify public relations practice. The essay calls for educators to tend to the development of the rhizome by modeling the conduct of compassionate and empathetic interactions in the classroom, and contingent, negotiated, dialogic, knowledge and beliefs.

Objective With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Setting Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). Methods As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. Perspective The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Conclusions Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

OBJECTIVE: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (eg, pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain.SETTING: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM).METHODS: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions.PERSPECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms.CONCLUSIONS: Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50,30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites.

The use of zebrafish (Danio rerio) in biomedical research has expanded at a tremendous rate over the last two decades. Along with increases in laboratories using this model, we are discovering new and important diseases. We review here the important pathogens and diseases based on some 20 years of research and findings from our diagnostic service at the NIH-funded Zebrafish International Resource Center. Descriptions of the present status of biosecurity programmes and diagnostic and treatment approaches are included. The most common and important diseases and pathogens are two parasites, Pseudoloma neurophilia and Pseudocapillaria tomentosa, and mycobacteriosis caused by Mycobacterium chelonae, M. marinum and M. haemophilum. Less common but deadly diseases are caused by Edwardsiella ictaluri and infectious spleen and kidney necrosis virus (ISKNV). Hepatic megalocytosis and egg-associated inflammation and fibroplasia are common, apparently non-infectious, in zebrafish laboratories. Water quality diseases include supersaturation and nephrocalcinosis. Common neoplasms are spindle cell sarcomas, ultimobranchial tumours, spermatocytic seminomas and a small-cell carcinoma that is caused by a transmissible agent. Despite the clear biosecurity risk, researchers continue to use fish from pet stores, and here, we document two novel coccidia associated with significant lesions in zebrafish from one of these stores.

Pseudocapillaria tomentosa is an important pathogen in zebrafish facilities. We investigated heat, ultraviolet (UV) light, chlorine, iodine, and dessciation for killing the parasite's eggs. Eggs released with feces larvate in about 5–10 days, and treatments were evaluated by exposing fresh eggs and subsequently comparing larvation to untreated eggs as an indication of survival. Collectively, untreated eggs in all trials showed high levels of survival. Eggs were exposed to elevated temperatures (40°C, 45°C and 50°C) for 1, 8, or 24 h, which resulted in substantial reduction in viability of eggs. UV radiation was effective, with no larvation at 50–300 mWs/cm(2) and

Objective To determine if the perioperative administration of valproic acid reduces the incidence of chronic pain three months after amputation or revision surgery. Design Multicenter, randomized, double-blind, placebo-controlled trial. Setting Academic, military, and veteran medical centers. Subjects One hundred twenty-eight patients undergoing amputation or amputation revision surgery at Duke University Hospital, Walter Reed National Military Medical Center, or the Durham Veterans Affairs Medical Center for either medical disease or trauma. Methods Patients were randomized to placebo or valproic acid for the duration of hospitalization and treated with multimodal analgesic care, including regional anesthetic blockade. Primary outcome was the proportion of patients with chronic pain at three months (average numeric pain score intensity of 3/10 or greater). Secondary outcomes included functional trajectories (assessed with the Brief Pain Inventory short form and the Defense and Veterans Pain Rating Scale). Results The overall rate of chronic pain was 68.2% in the 107 patients who completed the end point assessment. There was no significant effect of perioperative valproic acid administration, with a rate of 65.45% (N = 36) in the treatment group and a rate of 71.15% (N = 37) in the placebo group. Overall, pain scores decreased from baseline to follow-up (median = –2 on the numeric pain scale). Patients additionally experienced improvements in self-perceived function. Conclusions The rate of chronic pain after amputation surgery is not significantly improved with the perioperative administration of valproic acid. In this cohort treated with multimodal perioperative analgesia and regional anesthetic blockade, we observed improvements in both pain severity and function.

Pseudocapillaria tomentosa is a pathogenic nematode parasite, causing emaciation and severe inflammatory lesions in the intestines in zebrafish Danio rerio (Hamilton 1822). Emamectin benzoate is commercially available analogue of ivermectin used for treating salmon for sea lice, under the brand name SLICE® , and we have used this for treating zebrafish with the P. tomentosa. Here, SLICE® , 0.2 per cent active emamectin benzoate, was used for oral treatments at 0.35 mg emamectin benzoate/kg fish/day for 14 days starting at 7 days post-exposure (dpe). Another experiment entailed initiating treatment during clinical disease (starting at 28 dpe). Early treatment was very effective, but delaying treatment was less so, presumably due to inappetence in clinically affected fish. We evaluated emamectin benzoate delivered in water, using Lice-Solve™ (mectinsol; 1.4% active emamectin benzoate) in two experiments. Application of four 24-hr treatments, space over 7 days was initiated at 28 dpe at either 0.168 or 0.56 mg emamectin benzoate/L/bath, and both treatments completely eradicated infections. This was 3 or 10 times manufacture's recommended dose, but was not associated with clinical or histological side effects.

Enhanced recovery pathways have quickly become part of the standard of care for patients undergoing elective surgery, especially in North America and Europe. One of the central tenets of this multidisciplinary approach is the use of multimodal analgesia with opioid-sparing and even opioid-free anesthesia and analgesia. However, the current state is a historically high use of opioids for both appropriate and inappropriate reasons, and patients with chronic opioid use before their surgery represent a common, often difficult-to-manage population for the enhanced recovery providers and health care team at large. Furthermore, limited evidence and few proven successful protocols exist to guide providers caring for these at-risk patients throughout their elective surgical experience. Therefore, the fourth Perioperative Quality Initiative brought together an international team of multidisciplinary experts, including anesthesiologists, nurse anesthetists, surgeons, pain specialists, neurologists, nurses, and other experts with the objective of providing consensus recommendations. Specifically, the goal of this consensus document is to minimize opioid-related complications by providing expert-based consensus recommendations that reflect the strength of the medical evidence regarding: (1) the definition, categorization, and risk stratification of patients receiving opioids before surgery; (2) optimal perioperative treatment strategies for patients receiving preoperative opioids; and (3) optimal discharge and continuity of care management practices for patients receiving opioids preoperatively. The overarching theme of this document is to provide health care providers with guidance to reduce potentially avoidable opioid-related complications including opioid dependence (both physical and behavioral), disability, and death. Enhanced recovery programs attempt to incorporate best practices into pathways of care. By presenting the available evidence for perioperative management of patients on opioids, this consensus panel hopes to encourage further development of pathways specific to this high-risk group to mitigate the often unintentional iatrogenic and untoward effects of opioids and to improve perioperative outcomes.

Background Helminth parasites represent a significant threat to the health of human and animal populations, and there is a growing need for tools to treat, diagnose, and prevent these infections. Recent work has turned to the gut microbiome as a utilitarian agent in this regard; components of the microbiome may interact with parasites to influence their success in the gut, meaning that the microbiome may encode new anthelmintic drugs. Moreover, parasite infections may restructure the microbiome’s composition in consistent ways, implying that the microbiome may be useful for diagnosing infection. The innovation of these utilities requires foundational knowledge about how parasitic infection, as well as its ultimate success in the gut and impact on the host, relates to the gut microbiome. In particular, we currently possess limited insight into how the microbiome, host pathology, and parasite burden covary during infection. Identifying interactions between these parameters may uncover novel putative methods of disrupting parasite success. Results To identify interactions between parasite success and the microbiome, we quantified longitudinal associations between an intestinal helminth of zebrafish, Pseudocapillaria tomentosa, and the gut microbiome in 210 4-month-old 5D line zebrafish. Parasite burden and parasite-associated pathology varied in severity throughout the experiment in parasite-exposed fish, with intestinal pathologic changes becoming severe at late time points. Parasite exposure, burden, and intestinal lesions were correlated with gut microbial diversity. Robust generalized linear regression identified several individual taxa whose abundance predicted parasite burden, suggesting that gut microbiota may influence P. tomentosa success. Numerous associations between taxon abundance, burden, and gut pathologic changes were also observed, indicating that the magnitude of microbiome disruption during infection varies with infection severity. Finally, a random forest classifier accurately predicted a fish’s exposure to the parasite based on the abundance of gut phylotypes, which underscores the potential for using the gut microbiome to diagnose intestinal parasite infection. Conclusions These experiments demonstrate that P. tomentosa infection disrupts zebrafish gut microbiome composition and identifies potential interactions between the gut microbiota and parasite success. The microbiome may also provide a diagnostic that would enable non-destructive passive sampling for P. tomentosa and other intestinal pathogens in zebrafish facilities. Electronic supplementary material The online version of this article (10.1186/s40168-019-0622-9) contains supplementary material, which is available to authorized users.

Organizations and individuals need to engage their communities to gain the social license to operate (SLO). In crowdfunding, SLO is reflected in funding by the members of communities of interest around crowdfunding campaigns. Thus campaign creators’ success relies on obtaining SLO from their communities. This article examines how crowdfunding campaign creators engage their communities to gain and maintain SLO to secure funding for their campaigns. Content analysis of 68 successful and unsuccessful Kickstarter campaigns shows how successful campaign creators build their communities by the use of weak ties and have abundant relational and episodic engagement with their communities to obtain SLO. The results also show how successful campaign creators practice dialogic engagement to maintain their SLO over time. This study expands public relations to crowdfunding by framing crowdfunding as a community engagement practice and operationalizing SLO as tangible funding.

This paper challenges four assumptions in the public relations literature about dialogue: first, that dialogue means two-way communication; second, that dialogue is the same as two-way symmetry; third, that dialogue is the right answer to any troubled communication situation, and finally, fourth, the assumption that everyone agrees dialogue is a specific form of communication characterized by particular tenets, and with a long and distinguished ancestry reaching back to Ancient Greece. The four assumptions mean that over the last decade, dialogue has been implicitly and explicitly treated as both a panacea for public relations, and a practice that is impractical and too difficult to use. This article attempts to reconcile the various dialogic perspectives by specifying the tenets of dialogue, and using them to explain why two-way communication and two-way symmetry are not dialogue. We then challenge the normative bias in current conceptualizations of dialogue in public relations by identifying the existence of what we call “negative spaces,” or contexts, where dialogue is not possible or appropriate.

Pseudocapillaria tomentosa is a common pathogen of zebrafish (Danio rerio) in research facilities. We developed a method to collect and concentrate the nematode eggs using a modified sugar centrifugation method and documented their normal development. Embryonating stages with blastomere formation followed by elongation of the embryo prior to larva formation cumulated in developed larvae inside the eggs and hatching after 5-10 day. We then evaluated the efficacy of heat and chlorine to kill them based on a larva development assay. Eggs were exposed to 40, 50, 60 °C for 30 min and 1 h. Chlorine treatment was performed at 100, 250, 500, 1000, 3000 and 6000 ppm for 10 min. Samples exposed to 40 °C for 30 min or 1 h showed incidences of larvated eggs similar to controls. In contrast, no larvation occurred with eggs exposed to either 50 or 60 °C for 30 min or 1 h. Remarkably, in repeated assays, samples exposed to low doses of chlorine (100, 250, 500 and 1000 ppm for 10 min) showed significantly higher incidence of larvation than controls. Eggs treated with 3000 ppm for 10 min did not develop larvae, and no eggs were found after 6000 ppm treatment.

Objective. The Defense and Veterans Pain Rating Scale (DVPRS 2.0) is a pain assessment tool that utilizes a numerical rating scale enhanced by functional word descriptors, color coding, and pictorial facial expressions matched to pain levels. Four supplemental questions measure how much pain interferes with usual activity and sleep, and affects mood and contributes to stress. Methods. Psychometric testing was performed on a revised DVPRS 2.0 using data from 307 active duty service members and Veterans experiencing acute or chronic pain. A new set of facial representations designating pain levels was tested. Results. Results demonstrated acceptable internal consistency reliability (Cronbach’s alpha = 0.871) and test-retest reliability (r = 0.637 to r = 0.774) for the five items. Excellent interrater agreement was established for correctly ordering faces depicting pain levels and aligning them on the pain intensity scale (Kendall’s coefficient of concordance, W = 0.95 and 0.959, respectively). Construct validity was supported by an exploratory principal component factor analysis and known groups validity testing. Most participants, 70.9%, felt that the DVPRS was superior to other pain rating scales. Consclusion. The DVPRS 2.0 is a reliable and valid instrument that provides standard language and metrics to communicate pain and related outcomes.

Grass carp Ctenopharyngodon idella are sometimes used as a biological tool for managing aquatic vegetation in reservoirs. Sterile, triploid fish were stocked in Devils Lake, Oregon, during 1986, 1987, and 1993 to control aquatic vegetation. We present a case study for using multiple measures on the same fish to determine whether illegal stocking of fertile, diploid grass carp occurred. An investigation into the estimated age of a dead grass carp found in Devils Lake suggested that it was significantly younger than would otherwise be expected, given the only stocking events occurred during 1986, 1987, and 1993. To determine whether illegal stocking or reproduction by presumed sterile grass carp had occurred in Devils Lake, we conducted a study that balanced the needs of lethally sampling grass carp for biological measures with the socially and politically sensitive sentiment of the pro–grass carp citizenry of Devils Lake. These considerations, in combination with a low catch per-unit effort, resulted in a modest sample size for grass carp. We sampled grass carp and recorded multiple measures for each fish. Ploidy testing of blood samples indicated the grass carp were all triploid. Based on gonadal histopathology, six fish were male, two were female, and two were sex-indeterminate with severe gonadal dysgenesis. Age estimates from lapillus otoliths were consistent with fish originating from the legal stocking events in Devils Lake. The grass carp were 21–30 y old, and we were unable to find published reports of grass carp anywhere else in the world that are older. The grass carp were significantly smaller than much younger fish from other regions. The small size of these grass carp relative to their age in Devils Lake suggests food limitations that stunted growth. The dead grass carp that was the impetus for this study was aged by anatomical structures that we have since found to be unreliable. This suggests that the dead grass carp was probably in fact older and originated from the legal stockings. The use of multiple biological measurements on a modest sample size of grass carp, combined with the knowledge that no juvenile grass carp have been observed since legal stocking occurred, lead us to conclude that the grass carp in Devils Lake are sterile fish that originated from legal stocking events.

Public relations is among the least-respected professions in the world. Despite this uncomfortable fact, little research has seriously considered that public relations is perceived as a “dirty” profession, and how that perception translates into difficulties for public relations academics. Scholarship has not examined the lived experiences of public relations professors and how we reconcile our sense of self and self-respect in the mixed academic and professional environments that are often (un)intentionally disconfirming to our chosen area of study. Thus, this critical and self-reflexive essay takes up the challenge of dealing with the issues of disconfirmation, cognitive dissonance, and emotional labor that may be experienced by public relations professors in their interactions with colleagues, students, and even family members or friends.