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Several small freshwater fish species are utilized as models for human conditions and disease in biomedical research. Research animal diets are generally tailored to optimize growth, fecundity, and produce healthy research animals. However, a lack of reference diets presents a barrier in comparative studies between aquatic animal models and even among laboratories using the same species. Therefore, the objective of this study was to determine feeding regime and dietary effects on growth and fecundity in two commonly used freshwater fish, platyfish and medaka. From 1 through 6 months of age, platyfish and medaka were fed one of three feeding regime/diets: (1) our custom feeding regime consists of commercial flake food, beef liver paste, and live brine shrimp (CON); (2) a commercially available zebrafish diet, Gemma (GEM); and (3) a laboratory defined reference feeding regime (WAT). Weight, size, brood numbers, and survival rates for both species were measured monthly. Numbers of platyfish fry and hatch rate of medaka embryos were also determined. We observed that custom feeding regime (CON) fed platyfish and medaka grew larger, exhibited a higher survival rate, and had higher fecundity than WAT or GEM fed fish. These observations suggest that diets and regimes designed for zebrafish are not optimal to maintain platyfish or medaka. Thus, base diets, with clearly defined components and regimes, need to be developed with compositions that can be adjusted in a species-specific manner.

PURPOSE Continued opioid use after total knee and hip arthroplasty (TKA/THA) is well-documented and associated with both surgical and patient-reported factors. Research examining the combined effects of a multitude of factors on continued, and even chronic, opioid use in a systematic algorithmic manner is lacking. This study prospectively evaluated the combined effect of patient-related and surgical factors associated with continued opioid use after TKA/THA. METHODS From 2016 to 2018, 198 participants undergoing TKA or THA were recruited from two tertiary care facilities. Participants completed surveys before surgery and at 2 weeks, 1, 3, and 6 months following surgery. A LASSO approach, followed by an exhaustive covariate selection procedure, was used to build a multivariable mixed-effects logistic regression model estimating the odds ratio of continued postoperative opioid use based on surgical factors and patient-reported factors. RESULTS Approximately half of the participants underwent either TKA (49%) or THA (51%). Preoperatively, 15% of participants reported taking opioid medication. Opioid use decreased from 68% at 2-week follow-up to 7% by 6 months. In addition, preoperative opioid use (95% CI 1.07-4.37), increased pain (95% CI 1.21-1.62), elevated preoperative Pain Catastrophizing Scale scores (95% CI 1.01-1.04), lower Physical Function scores (95% CI 0.87-0.95), and participants undergoing TKA, compared to THA, (95% CI 0.25-0.67) were found to be significantly associated with continued postoperative opioid use up to 6 months. CONCLUSION Preoperative opioid use, average pain, reduced physical function, and TKA were significantly associated with continued postoperative opioid use. Findings illustrate the need for preoperative and longitudinal assessment of patient-reported outcomes to mitigate poor postoperative pain outcomes. LEVEL OF EVIDENCE II.

Background Ongoing postoperative pain assessments are vital to optimizing pain management and attenuating the development of poor health outcomes after surgery. This study aimed to characterize acute multidimensional trajectories of pain impact on physical function, sleep, mood, and stress and to examine clinical characteristics and demographics associated with trajectory membership. Additionally, this study compared levels of pain intensity and prescription opioid use at 2 weeks and 1 month postoperatively across acute symptom trajectories. Methods Participants (N = 285) undergoing total knee arthroplasty, total hip arthroplasty, and spinal fusion procedures were recruited for this multisite prospective observational study. Longitudinal, joint k-means clustering was used to identify trajectories based on pain impact on activity, sleep, mood, and stress. Results Three distinct pain impact trajectories were observed: Low (33.7%), Improving (35.4%), and Persistently High (30.9%). Participants in the Persistently High impact trajectory reported pain interfering moderately to severely with activity, sleep, mood, and stress. Relative to other trajectories, the Persistently High impact trajectory was associated with greater postoperative pain at 1 month postoperatively. Preoperatively, participants in the Persistently High impact trajectory reported worse Pain Catastrophizing Scale scores and PROMIS Pain Interference, PROMIS Anxiety, and PROMIS Social Isolation scores than did participants presenting with other trajectories. No statistical differences in opioid use were observed across trajectories. Conclusions Variation in acute postoperative pain impact on activity, sleep, mood, and stress exists. Given the complex nature of patients’ postoperative pain experiences, understanding how psychosocial presentations acutely change throughout hospitalization could assist in guiding clinicians’ treatment choices and risk assessments.

Along with the growing number of laboratories that work with zebrafish (Danio rerio), it is necessary to have animals with good sanitary quality. Specific pathogens can interfere with the experimental results and in the life quality of the animals. Pseudoloma neurophilia is a parasite with high potential for interference in behavioural, morphology, toxicological and genetic research, and is very common in zebrafish facilities. With that, we implemented a protocol for the pathogen elimination in a genetically modified lineage (prop 1) using eggs from specific pathogen-free (SPF) wild-type fish (AB line) for in vitro fertilization, along with water recirculation equipment disinfection, appropriate PCR screening and back crossing protocols. This resulted in SPF prop 1 heterozygotes, which allowed us to move forward with subsequent crossings to develop homozygote prop 1 mutants for our research. Hence, this demonstrates a useful strategy for an individual research laboratory to rederive a specific mutant free line that is not available from other SPF laboratories.

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.

Pacific salmon (Oncorhynchus spp.) rearing in lakes and reservoirs above dams have been known to become heavily infected with an ectoparasitic copepod (Salmincola californiensis). Little is known about the factors that affect the parasite infection prevalence and intensity. However, previous research suggests that the parasite may negatively affect the fitness and survival of the host fish. The effect of water temperature, confinement and the density of the free-swimming infectious stage of S. californiensis, the copepodid, on infection prevalence and intensity was evaluated by experimentally exposing juvenile Chinook Salmon (O. tshawytscha). Infection rates observed in wild populations were achieved under warm water (15-16°C) and high copepodid density (150-300/L) treatment conditions. Infection prevalence and intensity were also significantly higher in larger fish. During the infection experiment, 4.5% of infected fish died within 54 days with mortality significantly related to copepod infection intensity. The potential for autoinfection was compared to cross-infection by cohabitation of infected fish with naïve fish. Previously infected fish had significantly greater infection intensity compared with naïve fish, indicating that infected fish can be reinfected and that they may be more susceptible than naïve fish.

Objectives Despite substantial research showing the bidrectional relationship between sleep and pain, there remains a dearth of research examining the role of perioperative pain management interventions in mitigating postoperative sleep disturbances. This secondary analysis of a prospective observational multisite study examined the association between peripheral nerve block (PNB) use during total knee or total hip arthroplasty (TKA/THA) procedures and postoperative pain and sleep outcomes. Materials and methods Adult patients undergoing TKA or THA procedures were recruited from 2 tertiary care facilities. Average pain and sleep disturbance scores were collected preoperatively and at 1- and 2-week postoperatively. Participants were not randomized to receive PNB. Postoperative outcomes were compared based on receipt of PNB during surgery. Structural equation modeling path analysis was utilized to model multiple co-occurring relationships, including mediation pathways between perioperative pain management approaches, pain, and postoperative sleep outcomes. Results Of the 197 participants, 53% received PNB. Mediation analyses indicated that PNB was indirectly associated with 1-week sleep disturbance via its effects on 1-week pain intensity (β=-0.02, 95% confidence interval [CI] -0.04, -0.001, P=0.04). In addition, PNB was indirectly associated with 2-week sleep disturbance, via its effects on 1-week pain intensity and 1-week sleep disturbance (β=-0.04, 95% CI -0.07, -0.02, P=0.04). Lastly, PNB was indirectly associated with 2-week pain intensity via its effects on 1-week pain intensity (β=-0.10, 95% CI -0.19, -0.02, P=0.02). Conclusions Receipt of PNB during TKA or THA was found to be associated with improved 1-week postoperative pain intensity, which in turn was found to be associated with lower sleep disturbances at both 1- and 2-week postoperative time points. Multimodal opioid sparing pain management interventions, capable of improving postoperative sleep, are vital to improving recovery and rehabilitation following arthroplasty.

Pseudoloma neurophilia is a critical threat to the zebrafish (Danio rerio) model, as it is the most common infectious agent found in research facilities. In this study, our objectives were two-fold: (1) compare the application of diagnostic tools for P. neurophilia and (2) track the progression of infection using PCR and histology. The first experiment showed that whole-body analysis by qPCR (WB-qPCR) can be a standardized process, providing a streamlined diagnostic protocol, without the need for extraction of specific tissues. Evaluating the course of infection in experimentally infected fish, we showed key dynamics in infection. Starting with a low dose exposure of 8000 spores/fish, the prevalence remained low until 92 days post-exposure (dpe), followed by a 30%-40% prevalence by histology or 40%-90% by PCR until the end of the experiment at 334 dpe. WB-qPCR positively detected infection in more fish than histology throughout the study, as WB-qPCR detected the parasite as early as 4 dpe, whereas it was undetected by histology until 92 dpe. We also added a second slide for histologic analyses, showing an increase in detection rate from 24% to 26% when we combined all data from our experiments, but this increase was not statistically significant.

There have been several significant new findings regarding Microsporidia of fishes over the last decade. Here we provide an update on new taxa, new hosts and new diseases in captive and wild fishes since 2013. The importance of microsporidiosis continues to increase with the rapid growth of finfish aquaculture and the dramatic increase in the use of zebrafish as a model in biomedical research. In addition to reviewing new taxa and microsporidian diseases, we include discussions on advances with diagnostic methods, impacts of microsporidia on fish beyond morbidity and mortality, novel findings with transmission and invertebrate hosts, and a summary of the phylogenetics of fish microsporidia.

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.

Objectives To investigate pain catastrophizing presentations up to 6 months postoperatively and subsequent changes in pain intensity and physical function. Design Prospective observational multisite study. Setting Two tertiary care facilities between 2016 and 2019. Participants : Adult patients (N=348) undergoing a mastectomy, thoracic surgery, total knee or hip arthroplasty, spinal fusion, or major abdominal surgery. Interventions Not applicable. Main Outcome Measures Pain Catastrophizing Scale scores, Defense and Veterans Pain Rating Scale, average pain intensity, and Patient Reported Outcomes Measurement Information System (PROMIS) physical function. Results Four pain catastrophizing trajectories were identified in 348 surgical patients during the 6 months of postoperative recovery: stable, remitting, worsening, and unremitting. Linear mixed-effects models found that the unremitting trajectory was associated with higher pain intensity over time. The average pain intensity of participants in the remitting trajectory was estimated to decrease at a faster rate over the 6 months after surgery than pain of other trajectories, despite participants reporting high preoperative Pain Catastrophizing Scale and pain scores. Worsening and unremitting trajectories were associated with reduced physical function. Preoperative average pain intensity scores were not associated with postoperative physical function scores, nor were participants’ preoperative physical function scores associated with average pain intensity scores postoperatively. Prolonged hospitalization, smoking, and preoperative opioid prescriptions were associated with the unremitting trajectory. Conclusions Findings suggest that preoperative pain catastrophizing scores alone may not be adequate for estimating long-term patient-reported outcomes during postoperative rehabilitation. Pain catastrophizing has a dynamic presentation and is associated with changes in pain intensity and physical function up to 6 months postoperatively. Routine assessments can inform the delivery of early interventions to surgical patients at risk of experiencing a pain catastrophizing trajectory associated with suboptimal outcomes during rehabilitation.

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.

Along with the growing number of laboratories that work with zebrafish (Danio rerio), it is necessary to have animals with good sanitary quality. Specific pathogens can interfere with the experimental results and in the life quality of the animals. Pseudoloma neurophilia is a parasite with high potential for interference in behavioural, morphology, toxicological and genetic research, and is very common in zebrafish facilities. With that, we implemented a protocol for the pathogen elimination in a genetically modified lineage (prop 1) using eggs from specific pathogen-free (SPF) wild-type fish (AB line) for in vitro fertilization, along with water recirculation equipment disinfection, appropriate PCR screening and back crossing protocols. This resulted in SPF prop 1 heterozygotes, which allowed us to move forward with subsequent crossings to develop homozygote prop 1 mutants for our research. Hence, this demonstrates a useful strategy for an individual research laboratory to rederive a specific mutant free line that is not available from other SPF laboratories.

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.

Responses of marine populations to climate conditions reflect the integration of a suite of complex and interrelated physiological and behavioral responses at the individual level. Many of these responses are not immediately reflected in changes to survival, but may impact growth or survival at later life stages. Understanding the broad range of impacts of rising CO2 concentrations on marine fishes is critical to predicting the consequences of ongoing ocean acidification. Walleye pollock (Gadus chalcogrammus) support the largest single-species fishery in the world and provide a critical forage base throughout north Pacific ecosystems. Previous studies of high CO2 effects on early life stages of walleye pollock have suggested a general resiliency in this species, but those studies focused primarily on growth and survival rates. Here, we expand on earlier studies with an independent experiment focused on walleye pollock larval development, swimming behavior, and lipid composition from fertilization to 4 weeks post-hatch at ambient (~ 425 µatm) and elevated (~ 1230 µatm) CO2 levels. Consistent with previous observations, size metrics of walleye pollock were generally insensitive to CO2 treatment. However, 4-week post-hatch larvae had significantly reduced rates of swim bladder inflation. A modest change in the swimming behavior of post-feeding larvae was observed at four, but not at 2 weeks post-hatch. Although there were no differences in overall lipid levels between CO2 treatments, the ratio of energy storage lipids (triacylglycerols) to structural membrane lipids (sterols) was lower among larvae reared at high CO2 levels. Although we observed higher survival to 4 weeks post-hatch among fish reared at high CO2 levels, the observations of reduced swim bladder inflation rates and changes in lipid cycling suggest the presence of sub-lethal effects of acidification that may carry over and manifest in later life stages. These observations support the continued need to evaluate the impacts of ocean acidification on marine fishes across a wide range of traits and life stages with replicated, independent experiments.

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.

Although zebrafish continue to increase in popularity as a vertebrate animal model for biomedical research, chronic infectious diseases in laboratory populations remain prevalent. The presence of pathogens such as Pseudocapillaria tomentosa, a parasitic nematode found in the intestine of infected zebrafish, can significantly influence experimental endpoints and negatively impact reproducibility of research findings. Thus, there is a need for screening tests for zebrafish with the sensitivity to detect even low levels of pathogens present in tissues. Assays based on the detection of DNA are commonly used for such screening tests. Newer technologies such as digital PCR provide an opportunity to improve the sensitivity and precision of these assays, so they can be reliably used to detect pathogen DNA in water, reducing the need for lethal testing. We have designed a qPCR-based assay with the sensitivity to detect less than 5 copies of the P. tomentosa SSU-rDNA gene in tissues of infected zebrafish and environmental DNA from aquarium water housing infected fish. In addition, we adapted this test to a dPCR platform to provide a precise quantification of P. tomentosa DNA and demonstrate the resistance of this assay to inhibitors commonly found in freshwater aquaria.

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.

Purpose The purpose of this prospective correlational study was to compare the psychometric properties of the Defense and Veterans Pain Rating Scale (DVPRS) and Patient-Reported Outcomes Measurement Information System (PROMIS) scales with those of traditional legacy scales over a longitudinal postoperative period in patients undergoing arthroscopic procedures. Methods Active-duty military personnel undergoing shoulder and knee arthroscopic procedures completed the DVPRS, PROMIS, and legacy scales preoperatively and again at 3 months postoperatively. Rolling correlation coefficients (rrm) were used to assess the concurrent validity between the DVPRS average pain scores and computer adaptive testing PROMIS scales (Anxiety, Depression, Pain Behavior, Pain Interference, Mobility, Sleep Disturbance, Satisfaction With Social Roles, and Upper Extremity Physical Function) and the legacy scales (American Shoulder and Elbow Surgeons [ASES] scale, Shoulder Activity Scale, International Knee Documentation Committee [IKDC] questionnaire, Single Assessment Numeric Evaluation [SANE], Marx Activity Rating Scale, and Veterans RAND 12-Item Health Survey). Results A total of 121 participants completed the scales preoperatively, 80 completed them at 3 months postoperatively, and 59 (49% of participants) completed them at both times. Rolling correlation coefficients between PROMIS Pain Interference (rrm = –0.41, P = .006), Satisfaction With Social Roles (rrm = 0.56, P Conclusions PROMIS scales measuring physical function, pain presentation, and other health domains showed acceptable concurrent validity with ASES and IKDC scores. By integrating the prospective collection of biopsychosocial PROMIS scales into practice, it is possible for clinicians in orthopaedic settings to assess changes in validated patient-reported outcomes to inform patient-centered care planning throughout the postoperative recovery period. Level of Evidence Level II, prospective comparative study (with not all participants completing follow-up).

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.

Parasitic infections are frequently observed in laboratory zebrafish, and some cause significant morbidity or effect research endpoints. This is somewhat surprising given the confined environment and the parasite-free water sources used in most facilities. However, laboratories often exchange fish among themselves with no knowledge of prior disease history, and many researchers still use zebrafish procured from pet fish dealers. Ten parasites are discussed here: two external protists (Piscinoodinium pillulare and Ichthyophthirius multifiliis), two Microsporidia Pseudoloma neurophilia and Pleistophora hyphessobriconis; the capillarid nematode Pseudocapillaria tomentosa, a myxozoan Myxidium streisingeri, and two trematodes, metacercariae of undetermined species and adult stages of Transversotrema patialense.

Zebrafish are used as a model organism for research on a growing and wide range of studies. They are also susceptible to a variety of bacterial and fungal infections that might occur in any closed-system aquaculture setting. It is ideal that infectious diseases are minimized, to limit losses due to disease, and the potential impacts of these infections on research endpoints. Mycobacteriosis is the most commonly occurring bacterial diseases of zebrafish, caused by several different species. Because virulence differs between Mycobacterium species and strains, it is important that the specific agent is identified. Edwardsiella ictaluri is less commonly reported in zebrafish, but because it is associated with acute and severe disease, it should be avoided and can typically be recognized in quarantine. Other bacterial and fungal infections tend to occur opportunistically when fish experience poor husbandry conditions or other physiological stress. Excluding these agents from a facility through quarantine and screening should be the focus of any control program. Once established, there are strategies for monitoring, isolation, and treatment that can assist in managing or eliminating these infections.