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Post-translational modifications (PTMs) diversify peptide structure and allow for greater flexibility within signaling networks. The cardiac neuromuscular system of the American lobster, Homarus americanus, is made up of a central pattern generator, the cardiac ganglion (CG), and peripheral cardiac muscle. Together, these components produce flexible output in response to peptidergic modulation. Here, we examined the role of PTMs in determining the effects of a cardioactive neuropeptide, myosuppressin (pQDLDHVFLRFamide), on the whole heart, the neuromuscular junction/muscle, the isolated CG, and the neurons of the CG. Mature myosuppressin and noncyclized myosuppressin (QDLDHVFLRFamide) elicited similar and significant changes in whole heart contraction amplitude and frequency, stimulated muscle contraction amplitude and the bursting pattern of the intact and ligatured neurons of the ganglion. In the whole heart, nonamidated myosuppressin (pQDLDHVFLRFG) elicited only a small decrease in frequency and amplitude. In the absence of motor neuron input, nonamidated myosuppressin did not cause any significant changes in the amplitude of stimulated contractions. In the intact CG, nonamidated myosuppressin elicited a small but significant decrease in burst duration. Further analysis revealed a correlation between the extent of modulation elicited by nonamidated myosuppressin in the whole heart and the isolated, intact CG. When the neurons of the CG were physically decoupled, nonamidated myosuppressin elicited highly variable responses. Taken together, these data suggest that amidation, but not cyclization, is critical in enabling this peptide to exert its effects on the cardiac neuromuscular system. [ABSTRACT FROM AUTHOR]

This document is an abstract from the Journal of Clinical & Translational Science. The first part of the abstract discusses a study on trauma patients and the prediction of venous thromboembolism (VTE) using different models. The study found that certain factors, such as surgery, age, and BMI, were predictors of VTE. The second part of the abstract discusses a study on a 3D-printed bone graft composite for maxillofacial reconstruction. The study optimized the properties of the hydrogel core and growth factor release for enhanced bone regeneration. The third part of the abstract discusses a study on the association between preoperative sleep disturbance (SD) and depression and 12-month disability and pain after lumbar spine surgery. The study found that SD and depression were independent predictors of these outcomes, and the combination of both had a significant impact on postoperative outcomes. [Extracted from the article]

The American lobster, Homarus americanus, cardiac neuromuscular system is controlled by the cardiac ganglion (CG), a central pattern generator consisting of four premotor and five motor neurons. Here, we show that the premotor and motor neurons can establish independent bursting patterns when decoupled by a physical ligature. We also show that mRNA encoding myosuppressin, a cardioactive neuropeptide, is produced within the CG. We thus asked whether myosuppressin modulates the decoupled premotor and motor neurons, and if so, how this modulation might underlie the role(s) that these neurons play in myosuppressin’s effects on ganglionic output. Although myosuppressin exerted dose-dependent effects on burst frequency and duration in both premotor and motor neurons in the intact CG, its effects on the ligatured ganglion were more complex, with different effects and thresholds on the two types of neurons. These data suggest that the motor neurons are more important in determining the changes in frequency of the CG elicited by low concentrations of myosuppressin, whereas the premotor neurons have a greater impact on changes elicited in burst duration. A single putative myosuppressin receptor (MSR-I) was previously described from the Homarus nervous system. We identified four additional putative MSRs (MSR-II–V) and investigated their individual distributions in the CG premotor and motor neurons using RT-PCR. Transcripts for only three receptors (MSRII–IV) were amplified from the CG. Potential differential distributions of the receptors were observed between the premotor and motor neurons; these differences may contribute to the distinct physiological responses of the two neuron types to myosuppressin. NEW & NOTEWORTHY Premotor and motor neurons of the Homarus americanus cardiac ganglion (CG) are normally electrically and chemically coupled, and generate rhythmic bursting that drives cardiac contractions; we show that they can establish independent bursting patterns when physically decoupled by a ligature. The neuropeptide myosuppressin modulates different aspects of the bursting pattern in these neuron types to determine the overall modulation of the intact CG. Differential distribution of myosuppressin receptors may underlie the observed responses to myosuppressin. [ABSTRACT FROM AUTHOR]

Background Context: No consensus exists for defining chronic preoperative opioid use. Most spine studies rely solely on opioid duration to stratify patients into preoperative risk categories.Purpose: The purpose of this study is to compare established opioid definitions that contain both duration and dosage to opioid models that rely solely on duration, including the CDC Guideline for Prescribing Opioids for Chronic Pain, in patients undergoing spine surgery.Study Design: This was a retrospective cohort study that used opioid data from the Tennessee Controlled Substance Monitoring Database and prospective clinical data from a single-center academic spine registry.Patient Sample: The study cohort consisted of 2,373 patients who underwent elective spine surgery for degenerative conditions between January 2011 and February 2017 and who completed a follow-up assessment at 12 months after surgery.Outcome Measures: Postoperative opioid use and patient-reported satisfaction (NASS Satisfaction Scale), disability (Oswestry/Neck Disability Index), and pain (Numeric Rating Scale) at 12 month follow-up.Methods: Six different chronic preoperative opioid use variables were created based on the number of times a prescription was filled and/or daily morphine milligram equivalent for the one year before surgery. These variables defined chronic opioid use as 1) most days for > 3 months (CDC), 2) continuous use for ≥ 6 months (Schoenfeld), 3) >4,500 mg for at least 9 months (Svendsen wide), 4) >9,000 mg for 12 months (Svendsen intermediary), 5) >18,000 mg for 12 months (Svendsen strict), 6) low-dose chronic (1-36 mg for >91 days), medium-dose chronic (36-120 mg for >91 days), and high-dose chronic (>120 mg for >91 days) (Edlund). Multivariable regression models yielding C-index and R2 values were used to compare chronic preoperative opioid use definitions by postoperative outcomes, adjusting for type of surgery.Results: Chronic preoperative opioid use was reported in 470 to 725 (19.8% to 30.6%) patients, depending on definition. The Edlund definition, accounting for duration and dosage, had the highest predictive ability for postoperative opioid use (77.5%), followed by Schoenfeld (75.7%), CDC (72.6%), and Svendsen (59.9% to 72.5%) definitions. A combined Edlund and Schoenfeld duration and dosage definition in post-hoc analysis, that included 3 and 6 month duration cut-offs, performed the best overall with a C-index of 78.4%. Both Edlund and Schoenfeld definitions explained similar amounts of variance in satisfaction, disability, and pain (4.2% to 8.5%). Svendsen and CDC definitions demonstrated poorer performance for patient-reported outcomes (1.4% to 7.2%).Conclusions: The Edlund definition is recommended for identifying patients at highest risk for postoperative opioid use. When opioid dosage is unavailable, the Schoenfeld definition is a reasonable choice with similar predictive ability. For patient-reported outcomes, either the Edlund or Schoenfeld definition is recommended. Future work should consider combing dosage and duration, with 3 and 6 month cutoffs, into chronic opioid use definitions. [ABSTRACT FROM AUTHOR]

Peptides are known to contribute to central pattern generator (CPG) flexibility throughout the animal kingdom. However, the role played by receptor diversity/complement in determining this functional flexibility is not clear. The stomatogastric ganglion (STG) of the crab, Cancer borealis , contains CPGs that are models for investigating peptidergic control of rhythmic behavior. Although many Cancer peptides have been identified, their peptide receptors are largely unknown. Thus, the extent to which receptor diversity/complement contributes to modulatory flexibility in this system remains unresolved. Here, a Cancer mixed nervous system transcriptome was used to determine the peptide receptor complement for the crab nervous system as a whole. Receptors for 27 peptide families, including multiple receptors for some groups, were identified. To increase confidence in the predicted sequences, receptors for allatostatin-A, allatostatin-B, and allatostatin-C were cloned, sequenced, and expressed in an insect cell line; as expected, all three receptors trafficked to the cell membrane. RT-PCR was used to determine whether each receptor was expressed in the Cancer STG. Transcripts for 36 of the 46 identified receptors were amplified; these included at least one for each peptide family except RYamide. Finally, two peptides untested on the crab STG were assessed for their influence on its motor outputs. Myosuppressin, for which STG receptors were identified, exhibited clear modulatory effects on the motor patterns of the ganglion, while a native RYamide, for which no STG receptors were found, elicited no consistent modulatory effects. These data support receptor diversity/complement as a major contributor to the functional flexibility of CPGs. Unlabelled Image • Transcriptomics was used to identify Cancer borealis neuronal peptide receptors. • 46 putative receptors encompassing 27 peptide families were identified. • 36 of the 46 receptors appear to be expressed in the stomatogastric ganglion. • Myosuppressin (receptors +) but not RYamide (receptors −) modulates STG output. • Receptor diversity likely contributes significantly to STG functional flexibility. [ABSTRACT FROM AUTHOR]

Recent genomic/transcriptomic studies have identified a novel peptide family whose members share the carboxyl terminal sequence -GSEFLamide. However, the presence/identity of the predicted isoforms of this peptide group have yet to be confirmed biochemically, and no physiological function has yet been ascribed to any member of this peptide family. To determine the extent to which GSEFLamides are conserved within the Arthropoda, we searched publicly accessible databases for genomic/transcriptomic evidence of their presence. GSEFLamides appear to be highly conserved within the Arthropoda, with the possible exception of the Insecta, in which sequence evidence was limited to the more basal orders. One crustacean in which GSEFLamides have been predicted using transcriptomics is the lobster, Homarus americanus. Expression of the previously published transcriptome-derived sequences was confirmed by reverse transcription (RT)-PCR of brain and eyestalk ganglia cDNAs; mass spectral analyses confirmed the presence of all six of the predicted GSEFLamide isoforms - IGSEFLamide, MGSEFLamide, AMGSEFLamide, VMGSEFLamide, ALGSEFLamide and AVGSEFLamide - in H. americanus brain extracts. AMGSEFLamide, of which there are multiple copies in the cloned transcripts, was the most abundant isoform detected in the brain. Because the GSEFLamides are present in the lobster nervous system, we hypothesized that they might function as neuromodulators, as is common for neuropeptides. We thus asked whether AMGSEFLamide modulates the rhythmic outputs of the cardiac ganglion and the stomatogastric ganglion. Physiological recordings showed that AMGSEFLamide potently modulates the motor patterns produced by both ganglia, suggesting that the GSEFLamides may serve as important and conserved modulators of rhythmic motor activity in arthropods. [ABSTRACT FROM AUTHOR]

Pain and disability can persist after spinal surgery for which physical therapy (PT) is commonly prescribed. Currently, there is limited evidence to support the effectiveness of postoperative PT following cervical spine surgery. The purpose of this study was to examine the association between attending outpatient PT during the postoperative period and patient-reported outcomes at 1 year following cervical spine surgery. Retrospective evaluation of prospectively collected data from a single-center, spine registry. A total of 767 participants undergoing anterior cervical discectomy and fusion (ACDF) or posterior laminectomy with or without fusion for a degenerative condition. The primary outcomes for this study were disability (Neck Disability Index: NDI), quality of life (EQ-5D), and neck and arm pain (11-point Numeric Rating Scale: NRS). Participants were enrolled into a spine registry prior to surgery and completed a preoperative assessment. Follow-up assessments occurred at 3 months and 1 year after surgery. A categorical variable to describe PT over the 1-year period was created (No PT [reference], PT 0-3 months only, PT 0-3 and 3-12 months, PT 3-12 months only). Linear mixed-effects models were used to examine the effect of PT group on outcomes over time (3 months and 1 year). All analyses controlled for preoperative outcome scores, time, age, gender, race, smoking status, insurance type, body mass index, ambulation status, comorbidities, duration of symptoms, surgery type, revision, discharge status, number of levels, ASA grade and preoperative depression/anxiety and narcotic use. Significance was set at p <.05. Over the 1-year period, 351 patients had no PT (46%), 193 had PT from 0-3 months only (25%), 138 had PT from 0-3 and 3-12 months (18%), and 85 had PT from 3-12 months only (11%). The mixed-effects models found no significant relationship between PT 0-3 months only and all patient-reported outcomes at 1-year compared to the No PT group (p >.05). Patients who had PT between 3-12 months only had NDI scores 5.8-points higher, EQ-5D scores 0.03-points lower, and neck and arm pain scores 0.98-points and 0.68-points higher than the No PT group (p <.01). Finally, the PT 0-3 and 3-12 months group had NDI scores 4.1-points higher, EQ-5D scores 0.03-points lower, and neck and arm pain scores 0.54-points and 0.40-points higher than the No PT group (p <.05). Results from a retrospective multivariable analysis suggest that there is no difference in 1-year patient-reported outcomes between patients who utilize PT during the first 3 months only and patients who have No PT after cervical spine surgery. However, attending postoperative PT later in recovery, between 3 and 12 months, appears to result in increased disability and pain at 1-year after surgery, after accounting for patient and clinical characteristics. While the differences between groups are statistically significant, they do not appear to be clinically significant based on established MCID values. Overall, results suggest that attending PT after surgery may not lead to improved patient-reported outcomes compared to No PT. Additional research is needed to determine subgroups of patients who might benefit from traditional PT or alternative rehabilitation approaches that are informed by a biopsychosocial model. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]