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Bats and rodents comprise two of the world's largest orders of mammals and the order Chiroptera (bats) has been implicated as a major reservoir of coronaviruses in nature and a source of zoonotic transfer to humans. However, the order Rodentia (rodents) also harbors coronaviruses, with two human coronaviruses (HCoV-OC43 and HCoV-HKU1) considered to have rodent origins. The coronavirus spike protein mediates viral entry and is a major determinant of viral tropism; importantly, the spike protein is activated by host cell proteases at two distinct sites, designated as S1/S2 and S2’. SARS-CoV-2, which is considered to be of bat origin, contains a cleavage site for the protease furin at S1/S2, absent from the rest of the currently known betacoronavirus lineage 2b coronaviruses (Sarbecoviruses). This cleavage site is thought to be critical to its replication and pathogenesis, with a notable link to virus transmission. Here, we examine the spike protein across coronaviruses identified in both bat and rodent species and address the role of furin as an activating protease. Utilizing two publicly available furin prediction algorithms (ProP and PiTou) and based on spike sequences reported in GenBank, we show that the S1/S2 furin cleavage site is typically not present in bat virus spike proteins but is common in rodent-associated sequences, and suggest this may have implications for zoonotic transfer. We provide a phylogenetic history of the Embecoviruses (betacoronavirus lineage 2a), including context for the use of furin as an activating protease for the viral spike protein. From a One Health perspective, continued rodent surveillance should be an important consideration in uncovering novel circulating coronaviruses.

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The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) has led the medical and scientific community to address questions surrounding the pathogenesis and clinical presentation of COVID-19; however, relevant clinical models outside of humans are still lacking. In felines, a ubiquitous coronavirus, described as feline coronavirus (FCoV), can present as feline infectious peritonitis (FIP)—a leading cause of mortality in young cats that is characterized as a severe, systemic inflammation. The diverse extrapulmonary signs of FIP and rapidly progressive disease course, coupled with a closely related etiologic agent, present a degree of overlap with COVID-19. This paper will explore the molecular and clinical relationships between FIP and COVID-19. While key differences between the two syndromes exist, these similarities support further examination of feline coronaviruses as a naturally occurring clinical model for coronavirus disease in humans.

The equine herpesvirus type 1 (EHV-1) ORF1 and ORF71 genes have immune modulatory effects in vitro. Experimental infection of horses using virus mutants with multiple deletions including ORF1 and ORF71 showed promise as vaccine candidates against EHV-1. Here, the combined effects of ORF1 and ORF71 deletions from the neuropathogenic EHV-1 strain Ab4 on clinical disease and host immune response were further explored. Three groups of EHV-1 naïve horses were experimentally infected with the ORF1/71 gene deletion mutant (Ab4ΔORF1/71), the parent Ab4 strain, or remained uninfected. In comparison to Ab4, horses infected with Ab4ΔORF1/71 did not show the initial high fever peak characteristic of EHV-1 infection. Ab4ΔORF1/71 infection had reduced nasal shedding (1/5 vs. 5/5) and, simultaneously, decreased intranasal interferon (IFN)-α, interleukin (IL)-10 and soluble CD14 secretion. However, Ab4 and Ab4ΔORF1/71 infection resulted in comparable viremia, suggesting these genes do not regulate the infection of the mononuclear cells and subsequent viremia. Intranasal and serum anti-EHV-1 antibodies to Ab4ΔORF1/71 developed slightly slower than those to Ab4. However, beyond day 12 post infection (d12pi) serum antibodies in both virus-infected groups were similar and remained increased until the end of the study (d114pi). EHV-1 immunoglobulin (Ig) G isotype responses were dominated by short-lasting IgG1 and long-lasting IgG4/7 antibodies. The IgG4/7 response closely resembled the total EHV-1 specific antibody response. Ex vivo re-stimulation of PBMC with Ab4 resulted in IFN-γ and IL-10 secretion by cells from both infected groups within two weeks pi. Flow cytometric analysis showed that IFN-γ producing EHV-1-specific T-cells were mainly CD8+/IFN-γ+ and detectable from d32pi on. Peripheral blood IFN-γ+ T-cell percentages were similar in both infected groups, albeit at low frequency (~0.1%). In summary, the Ab4ΔORF1/71 gene deletion mutant is less virulent but induced antibody responses and cellular immunity similar to the parent Ab4 strain.

Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much more than serological or antigenic variants, resulting in the effective presence of two distinct viruses. Here, we review the distinct differences in the S proteins of these viruses, which are likely to translate into distinct biological outcomes. We introduce a new concept related to the non-taxonomical classification and differentiation among FCoVs by analyzing and comparing the genetic, structural, and functional characteristics of FCoV and the FCoV S protein among the two serotypes and FCoV biotypes. Based on our analysis, we suggest that our understanding of FIP needs to consider whether the presence of these two distinct viruses has implications in clinical settings.

Background: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit., Methods: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed., Results: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections., Conclusions: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions., Competing Interests: Competing interests: HTB, MD: NIH NIAMS P30AR072579. AC, MD: Research Funding: RM1NS128956-01A1; Consultant: Swing Therapeutics, Scilex Pharmaceuticals. SS, MD: Consultant: SPR Therapeutics, Allergan, Inc. DS, MD: Advisory Board, Funded research: Scilex; Speaker: AbbVie. AN, MD: Speaker: Averitas Pharmaceuticals; Research: Saol Therapeutics. AA-E, MD: Consultant: Curonix. TD, MD: Research support: Biohaven, NIH; Consultant: Guidepoint Global; Speaker honorarium: Remedy Health Media. MSE, MD: Funded research: SPR Therapeutics; Consultant: Avanos, Abbott. TH, MD: Acella: Advisory board, speaker: Acella. CH, MD: Research grant: Nevro, Inc. CP, MD: Consulting: Mainstay Medical; Royalties, UpToDate. BS, MD: Consultant: State Farm, Carelon. AS, MD: NIH R34AR080279. MM, MD: Consultant: Juris Medicus. JAH, MD: Grants: Neiman Health Policy Institute (there is no number associated with this foundation grant; Consulting (last 12 months): Medtronic, Relievant, Persica; DMC Chair: Balt, Rapid Medical, Arsenal. AW, MD: Investigator-initiated grant, Goodblends, PA. DAP, MD: Consulting: Avanos, Boston Scientific, Medtronic, Nevro, and SI Bone. Research support: Avanos, Boston Scientific, Medtronic, Nevro, Stimgenics, Abbott. SPC, MD: Consulting (past 2 years): Avanos, Scilex, SPR, SWORD, Releviate (ended), Clearing (ended), Persica (inactive); Research funds paid to institution: Scilex, Avanos. TM, MD: Consultant, Interventional AnalgesiX. The remaining authors declare no competing interests., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors declare no conflicts of interest.

Antibiotic use is an important component in dairy herd management both to treat bacterial diseases and to maximize animal welfare. However, there is concern among scientists that antibiotic misuse and/or overuse by farmers might promote the emergence of resistant pathogens. We conducted a cross-sectional web-based questionnaire study with dairy farmers/managers in New York, USA to evaluate their (i) level of concern about antibiotic resistance and (ii) interest in adopting new judicious antibiotic use practices regarding mastitis treatment. A total of 118 responses were subjected to statistical analysis. The findings revealed that nearly half (45%) of study participants were undecided or disagreed that antibiotic resistance due to antibiotic use in dairy farming may negatively impact the health of dairy cattle. In contrast, the majority (78%) of participants self-reported that they do not treat with antibiotics at the first sign of mastitis, and the majority (66%) have either fully or partially implemented culture-based mastitis treatment on their farm. The self-reported adoption of culture-based mastitis treatment practices was statistically significantly associated with higher numbers of injectable and intramammary doses of antibiotics used on the participants' farms. These findings will aid future research investigations on how to promote sustainable antibiotic use practices in dairy cattle.

Objective: To determine if commonly used knee radiofrequency ablation (RFA) techniques would be able to completely denervate the knee joint., Methods: A comprehensive search of the literature on knee joint innervation was conducted using the databases Medline, Embase, and PubMed from inception through February 1, 2019. Google Scholar was also searched. Data on the origin, number of articular branches, course, distribution, and frequency of each nerve innervating the knee joint were extracted from the included studies and compared in order to identify variations., Results: Twelve studies of anterior knee joint innervation and six studies of posterior knee joint innervation were included. The anterior knee joint was innervated by 10 nerves and further subdivided into two parts (anteromedial and anterolateral) or four quadrants (superomedial, inferomedial, superolateral, and inferolateral) based on innervation patterns; the posterior knee joint was innervated by two or three nerves, most commonly via the popliteal plexus. There is a lack of precise, validated anatomic targets identifiable with fluoroscopy and ultrasound for knee diagnostic blocks and RFA. Only three of the 12 or potentially 13 nerves innervating the knee joint are targeted by commonly used knee RFA techniques., Conclusions: Commonly used knee RFA techniques would not be able to completely denervate the knee joint. It may not be necessary to capture all of the nerves, but only the nerves mediating a patient's pain. Further clinical studies are required to validate specific diagnostic blocks and evaluate clinical outcomes using rigorous diagnostic blocks and anatomically specific knee RFA techniques., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Piriformis syndrome is a form of sciatica caused by compression of the sciatic nerve by the piriformis muscle. It is a relatively uncommon, but not insignificant, cause of sciatica. The diagnosis of piriformis syndrome is complicated by the large differential diagnosis of low back and buttock pain with many diagnoses having overlapping symptoms. This narrative review highlights the relevant anatomy, history, physical exam maneuvers, electrodiagnostic findings, and imaging findings that are used to diagnose piriformis syndrome. Also discussed are posterior gluteal myofascial pain syndromes that mimic piriformis syndrome. The review then outlines the different treatment options for piriformis syndrome including conservative treatment, injections, and surgical treatment. In addition, it provides the reader with a clinical framework to better understand and treat the complex, and often misunderstood, diagnosis of piriformis syndrome., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

Local glucocorticoid injections are often used to treat joint, soft tissue, or spinal pain, but the systemic side effects associated with these injections are poorly understood and not well recognized. There are significant known risks to systemic administration of glucocorticoids. However, there are no guidelines that address issues of systemic absorption, overall systemic risks, or other side effects of locally injected glucocorticoids. For this review, a literature search was performed, and the available evidence on systemic absorption and clinical side effects of intra-articular and epidural glucocorticoids was synthesized. The goal was to improve clinical understanding of risks associated with these injections. Existing data suggest there is significant individual variability in the amount of systemic absorption and clinical effects of locally injected glucocorticoids. However, it is clear that both intra-articular and epidural injections can have systemic effects for weeks and that complications may be associated with their use, including Cushing syndrome, loss of bone density, infection, and hyperglycemia. The concurrent use of oral steroids, the number of injections, and the type and dose of glucocorticoids used all are important considerations in estimating risks. The total dose calculation of cumulative glucocorticoid exposure should include all local injections. Caution should be exercised when local glucocorticoid injections are used in higher risk patients, such as postmenopausal women, people with diabetes, and those considering surgery in the near term. Better provider awareness of possible systemic risks should improve decision making and informed consent with patients when considering intra-articular and epidural steroid injections for painful conditions. LEVEL OF EVIDENCE: IV., (© 2018 American Academy of Physical Medicine and Rehabilitation.)

Objective: To compare the percentage of sacral lateral branches (LBs) that would be captured if lesions were created by seven current sacroiliac joint (SIJ) radiofrequency ablation (RFA) techniques: three monopolar and four bipolar., Design: Cadaveric fluoroscopy study., Setting: Anatomy and surgical skills laboratories., Subjects: Forty cadaveric SIJs., Methods: LBs were exposed, radiopaque wires were sutured to LBs, and anterior-posterior fluoroscopic images through the S1 superior endplate were obtained. Lesions that would be created by 17 versions of seven current SIJ RFA techniques were mapped on the fluoroscopic images. These 17 versions were compared: 1) percentage of LBs that would be captured; 2) percentage of SIJ specimens in which 100% of LBs would be captured; and 3) percentage of LBs that would not be captured at each level (S1-S4)., Results: Both the mean LB and 100% capture rates were greater for the bipolar techniques (93.4-99.7% and 62.5-97.5%, respectively) than for the monopolar techniques (49.6-99.1% and 2.5-92.5%, respectively) evaluated. For the bipolar techniques, 1.5-29.2% of LBs would not be captured at S1 and 0% at S2-S4 vs 0-29.2% at S1-S4 for the cooled monopolar techniques vs 36.9-100% at S1-S4 for the conventional monopolar technique., Conclusions: The findings suggest that, if lesions were created, the RFA needle placement locations of the bipolar techniques evaluated may be capable of capturing all LBs, but those of the current monopolar techniques evaluated may not. Future in vivo imaging studies are required to compare the lesion morphology generated by different SIJ RFA techniques and correlate the findings with clinical outcomes.

Background: Current sacroiliac joint (SIJ) cooled radiofrequency (RF) is based on fluoroscopic anatomy of lateral branches (LBs) in three specimens. Recent studies confirm significant variation in LB positions., Objectives: To determine if common fluoroscopic needle placements for cooled SIJ RF are adequate to lesion all S1-3 LBs. If not, would different targets improve lesion accuracy?, Methods: The LBs of 20 cadavers were dissected bilaterally (40 SIJs), and 26 G radiopaque wires were sutured to the LBs. With a 10-mm radius ruler centered at each foramen, standard targets were assessed, as judged by a clockface on the right, for S1 and S2 at 2:30, 4:00, and 5:30 positions and at S3 at 2:30 and 4:00. Mirror image targets were assessed on the left. Assuming an 8-mm lesion diameter, the percentage of LBs that would not be ablated for each level was determined. Imaging through the superior end plate of S1 was compared against segment specific (SS) imaging., Results: Nine point four percent of LBs would not be ablated at S1 vs 0.99% at S2 vs 35% at S3, and 60% of the 40 SIJs would be completely denervated using current targets. SS imaging did not improve results. Alternate target locations could improve the miss rate to 2.8% at S1 and 0% at S3 and would ablate all LBs in 95% of SIJs., Conclusions: Using a conservative 8-mm lesion measurement, contemporary cooled RF needle targets are inadequate to lesion all target LBs. Modifications to current targets are recommended to increase the effectiveness of the procedure.

Epidural steroid injection (ESI) has been used to treat cervical radiculopathy for several decades. Generally, available studies demonstrate favorable results, although definitive evidence of efficacy is lacking. ESIs are not considered a first line treatment and are undertaken after non-interventional treatments have been adequately provided. In the cervical spine, where evidence of potential benefit is moderate and there is risk of major complication, non-interventional care is even more germane. This article reviews the available literature regarding risks and efficacy of ESIs for cervical radiculopathy, and aims to guide practitioners in treatment decisions for individual patients., (Published by Elsevier Inc.)

Discography is a purely diagnostic interventional procedure performed to confirm or refute the hypothesis that a specific lumbar disc is the predominant source of a patient's low back pain. In patients with severe low back pain, unresponsive to conservative care, discography is used when clinical evaluation suggests that the pain is emanating from the intervertebral disc and other sources of pain have been ruled out. The evidence for its use remains controversial. There is variability and subjectivity in discography techniques and diagnostic criteria, making some investigators question its validity. When standardized diagnostic criteria are used, however, the specificity of discography improves dramatically. Recently long-term side effects have been studied, and lumbar discography seems to increase disc degeneration and herniation as detected on magnetic resonance imaging. Although the clinical significance is unclear, it is an important risk to consider prior to performing discography, and changes in discography techniques may be indicated. Discography remains the only technique, however, that can be used to determine whether a patient's low back pain is emanating from the intervertebral disc and is a valid test when coupled with careful patient selection, strict adherence to standardized technique and diagnostic criteria, and consideration of possible long-term sequelae., (Copyright © 2010. Published by Elsevier Inc.)

Epidural steroid injection (ESI) has been used as a treatment for low back pain for over 50 years. In the last 10 to 15 years, there has been a significant increase in the use of ESIs for the treatment of low back pain and radicular pain without clear improvements in outcomes. Recent literature has focused on the use of ESIs as treatment for radicular pain associated with low back pain, with some studies showing benefit over control groups for limb symptoms. There is a lack of literature, however, to support the use of ESIs for the treatment of axial low back pain. The theoretical basis for their use, technical considerations, and the literature available for different approaches of access to the epidural space as pertaining to the treatment for low back pain without radiculopathy are reviewed., (Copyright © 2010. Published by Elsevier Inc.)

Objective: To determine the presence of lumbar multifidus atrophy and pain after successful lumbar medial branch radiofrequency neurotomy for zygapophysial joint mediated pain., Design: A prospective observational analysis of 5 patients who had undergone successful unilateral radiofrequency neurotomy (RFN) of the lumbar medial branch divisions of the lumbar dorsal rami. At 17 to 26 months after RFN, 3 blinded radiologists evaluated the relative composition and size of the multifidus muscle at different segmental levels on lumbar magnetic resonance imaging (MRI). They were asked to determine the lesioned levels by evidence of multifidus atrophy. The accuracy of predicting the correct side and level lesioned was evaluated., Setting: Private spine practice in Tyler, Texas., Patients: Five patients who had unilateral lumbar medial branch RFN for proven lumbar zygapophysial joint-mediated pain were selected., Interventions: MRI of the lumbar spine at a mean of 21 months (range, 17-26) after successful lumbar RFN., Outcome Measures: Multifidus atrophy on a lumbar MRI, pain assessment and use of cointerventions., Results: Diffuse lumbar multifidus atrophy was detectable with MRI. However, radiologists could not reliably predict the side and segments lesioned. Despite denervation of the multifidus, at 12 months after RFN all subjects had ongoing pain relief and did not require or request additional treatment., Conclusions: This preliminary study provides evidence that successful medial branch RFN for lumbar zygapophysial-mediated pain does cause initial denervation but no discernable segmental atrophy of the multifidus at long-term follow-up. Previous denervation and diffuse atrophy in these subjects was not associated with pain.

We describe a field investigation in New England that identified the emergence and epidemiology of new strains of multidrug-resistant Salmonella, Newport-MDRAmpC, and summarize the Center for Disease Control and Prevention's surveillance data for these infections. In Massachusetts, the prevalence of Newport-MDRAmpC among Salmonella serotype Newport isolates obtained from humans increased from 0% (0/14) in 1998 to 53% (32/60) in 2001 (P<.001). In a retrospective case-control study, infection with Newport-MDRAmpC was domestically acquired and was associated with exposure to a dairy farm. Isolates from both humans and cattle had indistinguishable or closely related antibiograms and pulsed-field gel electrophoresis patterns. Nationally, the prevalence of ceftriaxone-resistant Salmonella increased from 0.5% in 1998 to 2.4% in 2001; 85% of the isolates in 2001 were Newport-MDRAmpC, and at least 27 states have isolated these strains from humans, cattle, or ground beef. These data document the widespread emergence of Newport-MDRAmpC strains in the United States and show that the 5-fold increase in the prevalence of Salmonella resistant to expanded-spectrum cephalosporins, between 1998 and 2001, is primarily due to the emergence of Newport-MDRAmpC strains.

In a series of 116 Salmonella enterica Newport isolates that included 64 multidrug-resistant (MDR) isolates, automated ribotyping and pulsed-field gel electrophoresis (PFGE) discriminated MDR S. Newport with a sensitivity of 100% and 98% and specificity of 76% and 89%, respectively. Clustering of PFGE patterns (but not ribotyping) linked human and bovine cases. Automated ribotyping rapidly identified the MDR strain, and PFGE detected associations that aided epidemiologic investigations.