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Simple Summary Numerous electrotherapeutic methods are commonly used in complementary and alternative veterinary medicine, as well as in conventional veterinary medicine. In these methods, electrical currents are commonly used to affect nerves, muscles, bones, or other tissues. In a systematic literature review, we collected information from published articles on electrotherapies used in horses, dogs, and cats. After screening 5385 articles of potential interest, we identified 41 articles that contributed to answering the overriding question: What is the scientific evidence for electrotherapy in horses, dogs, and cats? For most of the therapies, the number of studies was low with small numbers of animals. Many of the studies were of insufficient scientific quality and the electrotherapy was applied in many different clinical conditions and therapeutic settings. This made it difficult to reach robust conclusions, except for one: no current electrotherapies have sufficiently strong scientific evidence to support clinical effects in the treatment of horses, dogs, or cats with conditions affecting muscles, joints, nerves, or bones. Based on limited promising results, we have listed some electrotherapies that could be evaluated in more detail in high-quality studies. Electrotherapy modalities are currently used in the treatment of animals, but the evidence base supporting their use has not yet been systematically reviewed. Cochrane guidelines, as adapted by the Swedish Agency for Health Technology Assessment and Assessment of Social Services, were followed for this systematic review. A literature search regarding all currently known electrotherapy modalities applied to horses, dogs, and cats was conducted for the years 1980-2020 using three databases: CABI, PubMed, and Web of Science Core Collection. Of the 5385 references found, 41 articles were included in the review: 13 papers on pulsed electromagnetic field therapy (PEMFT), 7 on neural electrical muscle stimulation (NEMS), 5 on transcutaneous electrical nerve stimulation (TENS), 4 on static magnets, 3 on interference, 2 each on percutaneous electrical neural stimulation (PENS), bioelectricity, and diathermy, and 1 each on micro-pulsed stimulation, capacitive coupled electrical stimulation, and microwave therapy. The literature per modality was limited in quantity (mean 3.7 papers). Half of the articles were assessed to have a high risk of bias (20 high, 7 moderate, and 14 low). The existing literature used a spectrum of indications and treatment parameters, which makes comparisons and drawing conclusions to support the use of these modalities in clinical practice challenging. The current scientific evidence is not sufficient to support the clinical effects of electrotherapies for any clinical indication in horses, dogs or cats. The selected suggestive results warrant further high-quality research on PEMFT, NEMS, TENS, and PENS.

‘Staggering disease’ is a neurological disease entity considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with’staggering disease’ from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (Apodemus sylvaticus). Our work indicates that RusV is the long-sought cause of feline ‘staggering disease’. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans.

Simple Summary Bacteria within the gastrointestinal tract communicate with the immune system and the brain, have a role in energy metabolism and are responsible for gastrointestinal health and gut wall integrity. Veterinary research has reported links between gut bacteria and health. The so-called good bacteria can maintain health while proliferation of pathogenic bacteria can occur in certain conditions, causing colitis, inflammation, colic and dysbiosis. Genetic sequencing of gut bacteria can be used to provide a picture of the composition of the gut microbiome. This information can be used to manage the diet to provide an environment where the good gut bacteria can thrive. This study showed that feeding a prebiotic nutritional supplement resulted in mean and median percent decreases in Bacteroidetes, increases in Firmicutes and the Firmicutes:Bacteroidetes ratio that were significantly greater than zero for the treated horses only. Supplemented horses (8/10) were more likely than control horses (2/10) to show an increase in Firmicutes of a >= 9% with >= 24% increase in Clostridia, >= 5% decrease in Bacteroidetes, >= 16% increase in the F:B ratio and >= 2% increase in Actinobacteria (p = 0.01). This provides useful information for further investigations on long-term effects on the microbiome and on health and racing-related outcomes. Next-generation sequencing (NGS) has been used to evaluate the effect of various interventions on the equine microbiome. The aim of this randomised blinded clinical trial was to determine if a prebiotic nutritional supplement would result in a change from baseline in the faecal microbiome composition of racing Thoroughbred horses in training being fed a high concentrate/grain-based diet to be more similar to that found in forage fed/pasture grazed horses. Thirty-two horses on one training yard were randomised to either receive the supplement or not. Faecal samples were collected at baseline, 6 and 12 weeks for NGS of the 16S ribosomal subunit gene. Twenty-two horses completed the trial, met the inclusion criteria and were included in the intention to treat analysis; 20 horses were included in the per protocol analysis. The mean and median percent decreases in Bacteroidetes, increases in Firmicutes and the Firmicutes:Bacteroidetes ratio were significantly greater than zero for the treated horses only. Supplemented horses (8/10) were more likely than control horses (2/10) to show an increase in Firmicutes of a >= 9% with >= 24% increase in Clostridia, >= 5% decrease in Bacteroidetes, >= 16% increase in the F:B ratio and >= 2% increase in Actinobacteria (RR = 4, 95% CI: 1.1-14.4, p = 0.01). This provides useful information for further investigations on long-term effects on the microbiome and on health and racing-related outcomes.

Pigs are considered to be the main reservoir for livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), which is a zoonotic opportunistic pathogen. As LA-MRSA is an occupational hazard, there is an incentive to control its spread in pig herds. Currently, knowledge about effective control measures which do not require culling the whole herd are limited, and the control strategies against LA-MRSA vary between countries. This study uses a stochastic compartment model to simulate possible control measures for LA-MRSA in a farrow-to-finish pig herd. The aims of the study were to (1) extend a previously published disease spread model with additional management and control measures; (2) use the extended model to study the effect of the individual LA-MRSA control measures on the within-herd LA-MRSA prevalence; (3) evaluate the effect of control measures when they are implemented in combinations. From the individual control measures tested in the study, thorough cleaning was found to be most effective in reducing the LA-MRSA prevalence in the herd. When the different control measures were combined, cleaning together with disease surveillance had the largest impact on reducing the LA-MRSA and a higher chance of causing disease elimination. The results of the study showed that achieving disease elimination once LA-MRSA had been introduced in the herd was challenging but was more likely when control measures were introduced early during the outbreak. This emphasises the importance of early detection of the pathogen and subsequent rapid implementation of LA-MRSA control measures.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of The Animal Consortium. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BackgroundPre-emptive local analgesia with the use of lidocaine is practised increasingly in veterinary medicine as part of applied multimodal analgesia, despite its controversial impact on wound healing. The purpose of this prospective, randomised, double-blinded, placebo-controlled clinical study was to evaluate if preoperative subcutaneous infiltration of lidocaine has a negative impact on primary wound healing of surgical incisions. Fifty-two companion animals (3 cats and 49 dogs) were enrolled in the study. The inclusion criteria were as follows: American Society of Anaesthesiologists (ASA) score I or II, a minimum body weight of 5 kg, and a planned incisional length of at least 4 cm. Surgical incisions were infiltrated subcutaneously with lidocaine without adrenaline or NaCl (placebo). Follow-up questionnaires for owners and veterinarians and thermography of the surgical wound were used to assess wound healing. Antimicrobial use was documented.ResultsThere was no significant difference in either the total score or the individual assessment points between the treatment and the placebo group on the owner or the veterinary questionnaires in regard to primary wound healing (P > 0.05 for all comparisons). No significant difference was found between the thermography results of the treatment and placebo group (P = 0.78), and there was no significant correlation between the total score from the veterinary protocol and thermography results (Spearman's correlation coefficient - 0.10, P = 0.51). Surgical site infections developed in 5/53 (9.4%) surgeries and its occurrence varied significantly between the treatment and the placebo group as all cases of infection were in the placebo group (P = 0.05).ConclusionThe results of this study indicate that lidocaine used as a local anaesthetic did not affect wound healing in patients with ASA scores I-II. The results suggest that lidocaine infiltration in surgical incisions can be safely used to reduce pain.

The use of 16S rRNA sequencing has revolutionised research on the microbiome. However, few studies using this method have been done on semen from healthy bulls. Such information is required to optimise addition of antibiotics to semen extenders to inhibit growth of bacteria. With the increasing emergence of antibacterial resistance, it is important to identify alternatives to antibiotics in semen preservation. Possible solutions are to use plant-based substances that exhibit antimicrobial properties or to separate spermatozoa from bacteria in semen samples. The aims of this thesis were to identify the seminal microbiome of healthy bulls, to assess individual differences and their influence on fertility as well as seasonal differences in the occurrence of bacteria and their possible impacts on sperm quality. A second aim was to explore alternatives to antibiotics to reduce bacteria, using plant extracts or by physical removal of bacteria from semen samples. The studies revealed individual differences in bull seminal microbiota that may be correlated with fertility. Seasonal differences were observed in the bacteria in commercial semen samples; however, no significant associations were found between specific bacteria and sperm quality. When evaluating alternatives to antibiotics, we noted that curcumin extract at a concentration of 5% reduced the bacterial count and had a slight positive effect on bull sperm kinematics without negatively affecting sperm viability. Single layer centrifugation (SLC) effectively removed bacteria from bull semen samples while simultaneously selecting good quality spermatozoa. More studies are needed to investigate the influence of certain bacteria on bull sperm quality. The effects of combinations of plant-based substances on bacterial reduction and sperm quality could be investigated, and also further possibilities with SLC. These methods could contribute to reducing the development of antimicrobial resistance.

Objectives Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD). Methods RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities. Results Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures. Conclusion We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.

Objectives To evaluate the 1-year cost-effectiveness between three different initial treatment strategies in autoantibody-negative RA patients, according to 2010 criteria. Methods For this analysis we selected all RA patients within the intermediate probability stratum of the treatment in the Rotterdam Early Arthritis Cohort (tREACH) trial. The tREACH had a treat-to-target approach, aiming for low DAS Results Average quality-adjusted life-years (s.d.), for iMTX, iHCQ and iGCs were respectively 0.71 (0.14), 0.73 (0.14) and 0.71 (0.15). The average total costs (s.d.) for iMTX, iHCQ and iGCs were, respectively, €10 832 (14.763), €11 208 (12.801) and €10 502 (11.973). Healthcare costs were mainly determined by biological costs, which were significantly lower in the iHCQ group compared with iGCs (P Conclusion iHCQ had the lowest healthcare and highest productivity costs, resulting in a non-significant incremental cost-effectiveness ratio. However, iHCQ had the highest chance of being cost-effective at the Dutch willingness-to-pay threshold for healthcare reimbursement. Therefore, we believe that iHCQ is a good alternative to iMTX in autoantibody-negative RA patients, but validation is needed. Clinical trial registration number ISRCTN26791028

Pre-clinical models of disease have long played important roles in the advancement of new treatments. However, in traumatic brain injury (TBI), despite the availability of numerous model systems, translation from bench to bedside remains elusive. Integrating clinical relevance into pre-clinical model development is a critical step toward advancing therapies for TBI patients across the spectrum of injury severity. Pre-clinical models include in vivo and ex vivo animal work-both small and large-and in vitro modeling. The wide range of pre-clinical models reflect substantial attempts to replicate multiple aspects of TBI sequelae in humans. Although these models reveal multiple putative mechanisms underlying TBI pathophysiology, failures to translate these findings into successful clinical trials call into question the clinical relevance and applicability of the models. Here, we address the promises and pitfalls of pre-clinical models with the goal of evolving frameworks that will advance translational TBI research across models, injury types, and the heterogenous etiology of pathology.

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle. Genomic sequencing can resolve phylogenetic relationships between virus populations, which can be used to infer transmission routes and potentially inform the design of biosecurity measures. Sequencing of short (

Canine atopic dermatitis is an inflammatory skin disease with clinical similarities to human atopic dermatitis. Several dog breeds are at increased risk for developing this disease but previous genetic associations are poorly defined. To identify additional genetic risk factors for canine atopic dermatitis, we here apply a Bayesian mixture model adapted for mapping complex traits and a cross-population extended haplotype test to search for disease-associated loci and selective sweeps in four dog breeds at risk for atopic dermatitis. We define 15 associated loci and eight candidate regions under selection by comparing cases with controls. One associated locus is syntenic to the major genetic risk locus (Filaggrin locus) in human atopic dermatitis. One selection signal in common type Labrador retriever cases positions across the TBC1D1 gene (body weight) and one signal of selection in working type German shepherd controls overlaps the LRP1B gene (brain), near the KYNU gene (psoriasis). In conclusion, we identify candidate genes, including genes belonging to the same biological pathways across multiple loci, with potential relevance to the pathogenesis of canine atopic dermatitis. The results show genetic similarities between dog and human atopic dermatitis, and future across-species genetic comparisons are hereby further motivated.

Objective To assess predictors of subclinical RA-associated interstitial lung disease (RA-ILD) using quantitative lung densitometry (qLD). Methods RA patients underwent multi-detector row CT scanning at baseline and after an average of 39 months. Scans were analysed with qLD for the percentage of lung parenchyma with high attenuation areas (%HAA: the percentage of voxels of –600 to –250 Hounsfield units). Additionally, a pulmonary radiologist calculated an expert radiologist scoring (ERS) for RA-ILD features. Generalized linear models were used to identify indicators of baseline %HAA and predictors of %HAA change. Results Baseline %HAA was assessed in 193 RA patients and 106 had repeat qLD assessment. %HAA was correlated with ERS (Spearman’s rho = 0.261; P 10% of lung parenchyma with high attenuation) included female sex, higher pack-years of smoking, higher BMI and anti-CCP ≥200 units, collectively contributing an area under the receiver operator curve of 0.88 (95% CI 0.81, 0.95). Predictors of %HAA increase, occurring in 49% with repeat qLD, included higher baseline %HAA, presence of mucin 5B (MUC5B) minor allele and absence of HLA-DRB1 shared epitope (area under the receiver operator curve = 0.69; 95% CI 0.58, 0.79). The association of the MUC5B minor allele with %HAA change was higher among men and those with higher cumulative smoking. Within the group with increased %HAA, anti-CCP level was significantly associated with a greater increase in %HAA. Conclusions %HAA, assessed with qLD, was linked to several known risk factors for RA-ILD and may represent a more quantitative method to identify RA-ILD and track progression than expert radiologist interpretation.

Background: Sleep disturbances are prevalent in women living with HIV (WLWH) and can affect mental health and overall quality of life. We examined the prevalence and predictors of poor sleep quality in a US cohort of WLWH and HIV-uninfected controls and the relationship between sleep quality and mental health symptom burden stratified by HIV disease status (viremic WLWH, aviremic WLWH, and HIV-uninfected women). Methods: Sleep quality was assessed using the Pittsburgh Sleep Quality Index in 1583 (400 viremic WLWH, 723 aviremic WLWH, and 460 HIV-uninfected women) Women's Interagency HIV Study participants. Depressive and anxiety symptoms were concurrently assessed using the Center for Epidemiological Studies-Depression (CES-D) scale and General Anxiety Disorder (GAD-7) scale. Associations between poor sleep quality (global Pittsburgh Sleep Quality Index >5) and both high depressive (CES-D ≥16) and anxiety (GAD-7 ≥10) symptoms were each assessed by HIV disease status using multivariable logistic regression models. Results: Prevalence of poor sleep quality in the overall sample was 52%, differed by HIV disease status (P = 0.045), and was significantly associated with high depressive and anxiety symptoms in (1) viremic WLWH, (2) aviremic WLWH, and (3) HIV-uninfected women [CES-D: (1) adjusted odds ratio (aOR) = 7.50, 95% confidence interval (CI): 4.10 to 13.7; (2) aOR = 4.54, 95% CI: 3.07 to 6.73; and (3) aOR = 6.03, 95% CI: 3.50 to 10.4; GAD-7: (1) aOR = 5.20; 95% CI: 2.60 to 10.4, (2) aOR = 6.03; 95% CI: 3.67 to 9.91, and (3) aOR = 6.24; 95% CI: 3.11 to 12.6]. Conclusions: Poor sleep quality is highly prevalent, as is mental health symptom burden, among WLWH and HIV-uninfected controls. Future longitudinal studies are necessary to clarify the directionality of the relationship.

Objective To study the prevalence, risk and clinical associations of hypothyroidism among several forms of vasculitis. Methods Patients with GCA, Takayasu’s arteritis (TAK), PAN and the three forms of ANCA-associated vasculitis [AAV; granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA)] enrolled in a prospective, multicentre, longitudinal study were included. Results The study included data on 2085 patients [63% female, 90% White] with a mean age of 54.6 years (s.d. 17.2). Diagnoses were GCA (20%), TAK (11%), PAN (5%), GPA (42%), microscopic polyangiitis (8%) and EGPA (14%). Hypothyroidism was present in 217 patients (10%) (83% female), with a mean age 59.8 years (s.d. 14.5). Age- and sex-adjusted risk of hypothyroidism was GCA, odds ratio (OR) 0.61 (95% CI 0.41, 0.90); TAK, OR 0.57 (95% CI 0.31, 1.03); PAN, OR 0.59 (95% CI 0.25, 1.38); GPA, OR 1.51 (95% CI 1.12, 2.05); microscopic polyangiitis, OR 1.81 (95% CI 1.18, 2.80) and EGPA, OR 0.82 (95% CI 0.52, 1.30). Among patients with AAV, age- and sex-adjusted risk of hypothyroidism was higher with positive MPO-ANCA [OR 1.89 (95% CI 1.39, 2.76)]. The clinical manifestations of vasculitis were similar in patients with and without hypothyroidism, except transient ischaemic attacks, which were more frequently observed in patients with GCA and hypothyroidism (12% vs 2%; P = 0.001). Conclusions Differences in the risk of hypothyroidism among vasculitides may be due to genetic susceptibilities or immune responses. This study confirms an association of hypothyroidism with MPO-ANCA.

The Undergraduate Research in Natural and Clinical Science and Technology (URNCST) Journal Research Methods Primer is a novel undergraduate research design education opportunity available to undergraduate and professional-undergraduate degree students internationally. Applicants are invited to submit an abstract on a research method pre-selected by the journal and learn from a graduate-level researcher with expertise and interest in the research area. The three-month initiative is aimed at actively supporting and mentoring students as they navigate the complexities of research method theory and practice. The mentor and mentee(s) collaborate throughout the course of the program, culminating in the development of a full-length research methods primer manuscript of publishable quality. In this brief editorial, we provide an overview of how our editorial team successfully conceptualized, cultivated, and prepared for the launch of this initiative.

Objective To determine which baseline characteristics, especially clinically variables like pain, stiffness, physical functioning and disease variables, are associated with incident hip OA within 10 years in first presenters with hip complaints. Rheumatology key messages History taking and not physical exam variables are associated with incident hip osteoarthritis. Specific questions about daily life activities are associated with incident hip OA. These questions are about pain while walking/shopping, difficulties putting socks on/off and rising from bed. Methods Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study (n = 1002). Incident hip OA was defined as fulfilling the clinical ACR criteria for hip OA, a Kellgren and Lawrence score ≥2 with hip pain, or received a hip replacement during follow-up. Baseline measurements were used of participants with hip complaints and without hip OA. Principal component analysis (PCA) was used to reduce the number of correlated variables. Associations between baseline characteristics (including PCA components) and incident hip OA were investigated using logistic regression analysis, adjusted for age, sex and BMI. Results In total, 312 participants (85% female and 98% Caucasian) were included, 181 developed hip OA. PCA resulted in four components. Incident hip OA was associated with (i) component 1 (general presence of pain and symptoms) [odds ratio (OR) = 1.46 (95%CI: 1.08, 1.98)], (ii) component 3 (relatively high levels of pain during shopping/walking combined with less difficulty with putting socks on/off and rising from bed) [OR = 1.58 (95%CI: 1.18, 2.12)] and (iii) knee pain [OR = 0.34 (95% CI: 0.17, 0.66)]. Conclusion In first presenters with hip complaints, use of a few history-taking variables might allow better recognition of those at higher odds for incident hip OA within 10 years.

Objectives We evaluated the safety and efficacy of oral treprostinil in preventing progression of SSc-associated calcinosis. Methods This prospective open-label study enrolled 12 SSc patients meeting 2013 ACR/EULAR classification criteria with confirmed clinical and radiographic evidence of one or more calcinosis deposit in the hands. Patients received oral treprostinil for 1 year. Primary endpoints were safety/tolerability and percentage of patients without radiographic progression of calcinosis at 1 year ( Results Twelve female patients were enrolled, half with diffuse cutaneous disease; median age was 55 years (range 35–68 years). Five patients completed the study. Seven patients withdrew due to intolerable adverse effects (n = 3), intercurrent unrelated illness (n = 2, cirrhosis, cancer), progressive SSc (n = 1) and personal reasons (n = 1). Most patients developed headaches and gastrointestinal adverse effects. Four of 11 (36%) patients with 1-year follow-up hand radiographs experienced progression of calcinosis. Of five who completed treatment, calcinosis was stable in four (80%) with progression in one. Based on SF-36 Physical and Mental Component and Domain scores, transition question and SF-6D utility score, all patients who finished the trial reported overall improvement or no change compared with baseline. Conclusion Oral treprostinil was poorly tolerated in SSc patients with calcinosis. Of five patients who completed treatment, most (80%) had documented stability of calcinosis on hand radiographs at 1 year. ClinicalTrials.gov identifier NCT02663895.

Objectives: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). Design: A Phase 2b, multicenter, open-label, rollover study. Methods: LATTE participants with plasma HIV-1 RNA less than 50 copies/ml who completed at least 300 weeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA greater than or equal to 50 copies/ml at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements greater than or equal to 200 copies/ml), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. Results: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA greater than or equal to 50 copies/ml or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% (n = 77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. Conclusion: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5 years in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12.

BACKGROUND: The neurotransmitter serotonin (5-HT) affects valvular degeneration and dogs with myxomatous mitral valve disease (MMVD) exhibit alterations in 5-HT signaling. In Maltese dogs, 3 single nucleotide polymorphisms (SNPs) in the 5-HT transporter (SERT) gene are suggested to associate with MMVD.HYPOTHESIS/OBJECTIVES: Determine the association of SERT polymorphisms on MMVD severity and serum 5-HT concentration in Cavalier King Charles Spaniels (CKCS). Additionally, investigate the association between selected clinical and hematologic variables and serum 5-HT and assess the correlation between HPLC and ELISA measurements of serum 5-HT.ANIMALS: Seventy-one CKCS (42 females and 29 males; 7.8 [4.7;9.9] years (median [Q1;Q3])) in different MMVD stages.METHODS: This prospective study used TaqMan genotyping assays to assess SERT gene polymorphisms. Neurotransmitter concentrations were assessed by HPLC and ELISA.RESULTS: TaqMan analyses identified none of the selected SERT polymorphisms in any of the CKCS examined. Serum 5-HT was associated with platelet count (P CONCLUSIONS AND CLINICAL IMPORTANCE: Selected SERT SNPs associated with MMVD in Maltese dogs were not found in CKCS and only platelet count influenced serum 5-HT concentration. These SNPs are unlikely to be associated with MMVD pathophysiology or serum 5-HT concentration in CKCS. HPLC and ELISA serum 5-HT demonstrated good correlation but ELISA systematically underestimated 5-HT.

Background MK-8507 is a novel HIV-1 non-nucleoside reverse transcriptase inhibitor being developed for treatment of HIV-1 infection. MK-8507 has high antiviral potency in vitro and pharmacokinetic (PK) properties that support once-weekly dosing. Setting A phase 1, open-label, proof-of-concept study was conducted in treatment-naive adults with HIV-1 infection to assess monotherapy antiviral activity. Methods In 3 sequential panels, participants aged 18-60 years with baseline plasma HIV-1 RNA ≥10,000 copies/mL and CD4+ T-cell count >200/mm3 received a single oral dose of 40, 80, or 600 mg MK-8507 in the fasted state. Participants were assessed for HIV-1 RNA for at least 7 days, PK for 14 days, and safety and tolerability for 21 days post dose. Results A total of 18 participants were enrolled (6 per panel). The mean 7-day post-dose HIV-1 RNA reduction ranged from ∼1.2 to ∼1.5 log10 copies/mL across the doses assessed. One patient had a viral rebound associated with emergence of a F227C reverse transcriptase variant (per chain-termination method sequencing) 14 days post dose; this variant was found in a second participant by ultra-deep sequencing as an emerging minority variant. MK-8507 PK were generally dose-proportional and similar to observations in participants without HIV-1 infection in prior studies; mean MK-8507 half-life was 56-69 hours in this study. MK-8507 was generally well tolerated at all doses. Conclusions The robust antiviral activity, PK, and tolerability of MK-8507 support its continued development as part of a complete once-weekly oral regimen for HIV-1 treatment; combination therapy could mitigate the emergence of resistance-associated variants.

Objectives Many patients with axial spondyloarthritis (axSpA) report persistent pain even when treated with anti-inflammatory agents. Our aim was to explore the presence of central sensitization (CS) and different types of illness perceptions in patients with axSpA, and to assess their associations with disease activity assessments. Methods Consecutive outpatients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included. Besides standardized assessments, patients filled out the Central Sensitization Inventory (CSI), Illness Perception Questionnaire (IPQ-R) and Pain Catastrophizing Scale (PCS). Univariable and multivariable linear regression analyses were used to investigate the association between questionnaire scores, patient characteristics and disease activity assessments ASDASCRP, BASDAI and CRP. Results We included 182 patients with a mean symptom duration of 21.6 years. Mean ASDASCRP was 2.1, mean BASDAI 3.9, and median CRP 2.9. Mean CSI score was 37.8 (scale 0–100) and 45% of patients scored ≥40, indicating a high probability of CS. CSI score, IPQ-R domain identity (number of symptoms the patient attributes to their illness), and IPQ-R domain treatment control (perceived treatment efficacy), and obesity were significantly and independently associated with both ASDASCRP and BASDAI, explaining a substantial proportion of variation in these disease activity scores (R2=0.35 and R2=0.47, respectively). Only obesity was also independently associated with CRP. Conclusion CS may be common in patients with long-term axSpA. CS, as well as specific illness perceptions and obesity were all independently associated with the widely used (partially) patient-reported disease activity assessments ASDASCRP and BASDAI. Treating physicians should take this into account in the follow-up and treatment of their patients.

Objective We determined the prevalence of sarcopenic obesity in patients with RA using multiple methods and assessed associations with physical functioning. Methods This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the HAQ and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race and study. Results The prevalence of low lean mass and sarcopenic obesity was higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7–10%; 4–4.5%, respectively, all P Conclusion RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.

To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs. DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2.Design:Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks).Methods:Participants with HIV-1 RNA ≤500 000 copies/ml and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC.Results:At week 144, DTG + 3TC (N = 716) was noninferior to DTG + TDF/FTC (N = 717) in proportion of participants achieving HIV-1 RNA, This study was funded by ViiV Healthcare

Background: Data on HIV-1 controllers in Africa are scarce. We report the proportion of HIV-1 controllers in a group of adults prospectively monitored with frequent viral load measurements as part of a clinical trial in West Africa. Methods: For the Temprano trial, antiretroviral therapy (ART)-naive HIV-1 infected adults with no criteria for starting ART were randomized to start ART immediately or defer ART until the WHO starting criteria were met. Plasma viral load was measured every 6 months. The trial follow-up was 30 months. We considered all Temprano participants randomized to defer ART. Patients with all semestrial viral

Background Thymidine kinase 1 (TK1) catalyzes the initial phosphorylation of thymidine in the salvage pathway synthesis of dTTP, an essential building block of DNA. TK1 is a cytosolic enzyme with its highest level during the S-phase of the cell cycle. In cancer cells TK1 is upregulated and excess TK1 is leaked into the blood. Therefore, serum TK1 has been used as biomarker for cancer diagnosis and prognosis in human medicine. Feline TK1 shows high sequence similarity to TK1 from other species. The aim of this study was to characterize feline TK1 and evaluate if serum TK1 can be used as a diagnostic biomarker. Results Feline TK1 was cloned, expressed and affinity purified. The purified feline TK1 phosphorylated not only pyrimidine deoxyribonucleosides but also pyrimidine ribonucleosides and to some extent purine deoxynucleosides. A number of anticancer and antiviral nucleoside analogs also served as substrates with fairly high efficiency. ATP and dATP were the preferred phosphate donor. Serum TK1 activity in felines with malignant diseases was significantly higher than that in healthy individuals. ROC analysis revealed an area under the curve (AUC) of 0.98 with a sensitivity of 0.83 and a specificity of 0.95 for felines with lymphoma. Serum TK1 activity in felines with IBD or inflammatory disease was within the same range as healthy ones. Furthermore, in felines with lymphoma serum TK1 activity returned to normal levels in response to treatment. Conclusion Feline TK1 has high specific activity and a broader substrate specificity in comparison with TK1 from other species. Serum TK1 activity in felines with malignant diseases is significantly higher than that in normal felines and in felines with inflammatory diseases. These results suggest that serum TK1 may be a promising biomarker for the diagnosis and monitoring of malignant diseases and for the differential diagnosis of certain inflammatory disease.

Thrombosis after liver transplantation substantially impairs graft‐ and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome‐wide association study (GWAS) and meta‐analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis‐susceptible polymorphisms. By performing a meta‐GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611‐T, p = 4.22 × 10−05) which encodes a protein that regulates cellular ATP levels and concurrent activation of AMPK and mTOR, and RGS5 (rs10917696‐C, p = 2.62 × 10−05) which is involved in vascular development. We provide evidence that common genetic variants in the donor, but not previously known thrombophilia‐related variants, are associated with increased risk of thrombosis after liver transplantation., A meta‐analysis of two genome‐wide association studies of adult and pediatric liver transplants identifies three common candidate risk loci in the donor, but not previously known thrombophilia‐related variants, were newly associated with increased risk of thrombosis after liver transplantation.

Background and objectives Although US physician-scientists have made enormous contributions to biomedical research, this workforce is thought to be getting smaller. However, among kidney researchers, changes have not been fully quantified. Design, setting, participants, & measurements We mined National Institutes of Health RePORTER to explore demographic changes of early-career and established physician and nonphysician principal investigators doing kidney-focused research. We searched for National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-funded K series and R01 awards focused on the kidney that were active between 1990 and 2020 and determined if their emphasis was basic or clinical science. We then used public databases available on the internet to determine if these funded investigators were physicians or nonphysicians, the year in which they received either their MD (physicians) or their terminal graduate degree (nonphysicians), their sex, and whether they received their terminal degree from a US or international institution. Results Kidney-focused R01-funded principal investigators are aging, particularly among physicians. Moreover, the relative representation of physicians among both early-career and established principal investigators is falling, particularly among those doing basic science research. In contrast, the number and relative representation of nonphysician-scientists are increasing. There is also greater representation of women and international graduates among physician and nonphysician R01-funded, kidney-focused NIDDK investigators. However, although there are greater numbers of women physician principal investigators doing both basic as well as clinical research, women physician principal investigators are increasingly more likely to do clinical rather than basic science research. Conclusions The physician-scientist workforce is increasingly made up of women and international medical graduates. However, the physician-scientist workforce is older and represents a smaller proportion of all principal investigators, particularly among those doing basic science research.

In this interview, Dr Farah R Zahir speaks with Storm Johnson, Commissioning Editor for Epigenomics, on her work to date in the field of epigenomics, autism and intellectual disability. Dr Farah R Zahir specializes in the identification of novel genetic and epigenetic causes for neurodevelopmental diseases. Her PhD, awarded in 2011 by the University of British Columbia (UBC), resulted in the characterization of new intellectual disability (ID) syndromes, as well as discovery of several new causative genes for the disorder. She was awarded the prestigious James Miller Memorial Prize for integrating basic and clinical science in 2010. Her PhD dissertation was nominated for the Governor General’s gold medal – the highest possible accolade at UBC for doctoral research work. She then completed a postdoctoral tenure in Canada’s premier Michael Smith Genome Sciences Centre, where she used whole-genome-sequencing methods to comprehensively assess genetic, molecular and structural causes for ID, employing several firsts for bioinformatic data mining in the field. During her postdoctorate she won three distinguished awards and was a fellow of the Canadian Institute of Health Research, ranking in the top 2% nationally. Dr Zahir was appointed as an Assistant Professor at the Hamad Bin Khalifa University in 2016, where she led a group focused on neurogenomics and neuroepigenomics research. She was a founding member of the Precision and Genomics Medicine graduate program there. Currently she has rejoined UBC's department of Medical Genetics. Among her most significant achievements is the establishment of the novel Zahir Friedman syndrome, an intellectual disability/autism spectrum disorder syndrome that is caused by a major epigenomic regulator. Her current primary research interest is how epigenomics can be changed by environmental impacts and how these effects may be harnessed for neurodevelopmental disorders' prophylaxis and therapeutics.

Summary Anthelmintic resistance (AR) in equine cyathostomins is being reported all over the world. In Lithuania, however, the last study on this subject was published more than fifteen years ago, thus little is known about the current situation. The aim of this study was to determine the factors that may associated with the development of AR on equine studs in Lithuania. A questionnaire containing seven open-ended and nine closed multiple-choice questions about worm control strategies, use of anthelmintic substances and stable management practices was posted to 71 randomly selected horse establishments in Lithuania. Replies were obtained from a total of 59 stables, representing 83 % of officially established stud farms in Lithuania. The results showed that more than 80 % of these establishments performed pasture management practices such as excrement removal from stables and pasture, 56 % mowed their pasture, 31 % practised mixed or rotational grazing with other species, and 97 % of the horses were routinely dewormed. Macrocyclic lactones (ML) (58 %, n=33) were the most commonly used drugs, followed by benzimidazoles (BZ) (24 %, n=14) and tetrahydropyrimidines (THP) (19 %, n=10). The majority of farms (60 %) treated horses four times per year and 68 % estimated the weight of the horses by eye before treatment. About 36 % of respondents had heard of faecal egg counts (FEC), but only 17 % used the test and as few as 9 % had tested their herds for AR with faecal egg count reduction tests (FECRT). The results demonstrate that there is scope for improving routines for worm control in many horse establishments in Lithuania. In order to increase knowledge and reduce the risk of the spread of AR, diagnostic methods should be adopted in a collaboration between stud farms and veterinary practitioners.

Knowledge on the immunogenicity of vector‐based and mRNA‐vaccines in solid organ transplant recipients is limited. Therefore, SARS‐CoV‐2–specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine‐regimens. Plasmablasts and SARS‐CoV‐2–specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS‐CoV‐2–specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS‐CoV‐2–specific IgG‐ and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID‐19‐vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals., Among solid organ transplant recipients, a heterologous COVID‐19 vaccine regimen (adenovirus and mRNA vaccine) compared to homologous regimens (two adenovirus or two mRNA vaccines) induce both antibodies and CD4 T cell responses best and combined analysis of humoral and cellular immunity improves identification of responders.

After renal transplantation, there is a need for immunosuppressive regimens which effectively prevent allograft rejection, while preserving renal function and minimizing side effects. From this perspective, mesenchymal stromal cell (MSC) therapy is of interest. In this randomized prospective, single‐center, open‐label trial, we compared MSCs infused 6 and 7 weeks after renal transplantation and early tacrolimus withdrawal with a control tacrolimus group. Primary end point was quantitative evaluation of interstitial fibrosis in protocol biopsies at 4 and 24 weeks posttransplant. Secondary end points included acute rejection, graft loss, death, renal function, adverse events, and immunological responses. Seventy patients were randomly assigned of which 57 patients were included in the final analysis (29 MSC; 28 controls). Quantitative progression of fibrosis failed to show benefit in the MSC group and GFR remained stable in both groups. One acute rejection was documented (MSC group), while subclinical rejection in week 24 protocol biopsies occurred in seven patients (four MSC; three controls). In the MSC group, regulatory T cell numbers were significantly higher compared to controls (p = .014, week 24). In conclusion, early tacrolimus withdrawal with MSC therapy was safe and feasible without increased rejection and with preserved renal function. MSC therapy is a potentially useful approach after renal transplantation., TRITON, a randomized, prospective, single‐center, open‐label study, shows that autologous mesenchymal stromal cell therapy and early tacrolimus withdrawal was feasible and safe, without increased rejection and with preserved renal function.

Veterinary dental cleaning prevents and treats periodontal disease, one of the most common diagnoses in small animal practice. Students learn to perform dental cleaning through deliberate practice, which can be gained through working on models. This study compared educational outcomes after students ( n = 36) were randomized to practice on one of three dental cleaning models: a low-fidelity ceramic tile, a mid-fidelity three-dimensional (3D) printed canine skull model, or a high-fidelity canine head model. Students provided survey feedback about their model and later performed a dental cleaning on a canine cadaver head while being video-recorded. Experts ( n = 10) provided feedback on each model. Experts agreed that all models were suitable for teaching dental cleaning, but the 3D skull and full head models were more suitable for assessing student skill ( p = .002). Students were also more positive about the realism and features of those two models compared to the tile model. Students practicing on each of the models were equally effective at removing calculus from the cadavers’ teeth. Students who learned on the tile model were a median of 4 minutes slower to remove calculus from their cadaver’s teeth than students who trained on the canine head model. Although students may be more accepting of the 3D skull and full head models, all three models were equally effective at teaching the skill. Experts approved all models for teaching, but recommended the 3D skull or full head model if student skills were to be assessed. Low-fidelity models remain effective training tools with comparable learning outcomes.

Objectives We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. Methods This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. Results Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13–14%). Conclusion The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.

Supplemental Digital Content is Available in the Text., Background: The lack of acute and early HIV infection (AEHI) diagnosis and care contributes to high HIV incidence in resource-limited settings. We aimed to assess the yield of AEHI, predict and diagnose AEHI, and describe AEHI care outcomes in a public sector setting in Eswatini. Setting: This study was conducted in Nhlangano outpatient department from March 2019 to March 2020. Methods: Adults at risk of AEHI underwent diagnostic testing for AEHI with the quantitative Xpert HIV-1 viral load (VL) assay. AEHI was defined as the detection of HIV-1 VL on Xpert and either an HIV-seronegative or HIV-serodiscordant third-generation antibody-based rapid diagnostic test (RDT) result. First, the cross-sectional analysis obtained the yield of AEHI and established a predictor risk score for the prediction of AEHI using Lasso logistic regression. Second, diagnostic accuracy statistics described the ability of the fourth-generation antibody/p24 antigen–based Alere HIV-Combo RDT to diagnose AEHI (vs Xpert VL testing). Third, we described acute HIV infection care outcomes of AEHI-positive patients using survival analysis. Results: Of 795 HIV-seronegative/HIV-serodiscordant outpatients recruited, 30 (3.8%, 95% confidence interval: 2.6% to 5.3%) had AEHI. The predictor risk score contained several factors (HIV-serodiscordant RDT, women, feeling at risk of HIV, swollen glands, and fatigue) and had sensitivity and specificity of 83.3% and 65.8%, respectively, to predict AEHI. The HIV-Combo RDT had sensitivity and specificity of 86.2% and 99.9%, respectively, to diagnose AEHI. Of 30 AEHI-positive patients, the 1-month cumulative treatment initiation was 74% (95% confidence interval: 57% to 88%), and the 3-month viral suppression (

IntroductionThe Markhoz goat is the only breed that can produce high-quality fiber called mohair in Iran; however, the size of its population has faced a dramatic decline during the last decades, mainly due to the reluctance of farmers to rear Markhoz goats caused by a reduction in goat production income. Litter size at birth (LSB) and weaning (LSW) are two economically important reproductive traits for local goat breeders and have the potential of increasing the population growth rate. The present study was aimed to identify possible genomic regions that are associated with LSB and LSW in Markhoz goats using a genome-wide association study (GWAS).MethodsTo this end, 136 Markhoz goats with record(s) of kidding were selected for GWAS using the Illumina Caprine 50K bead chip. The individual breeding values (BV) of available LSB and LSW records estimated under an animal mixed model were used as the dependent variable in the GWAS, thereby incorporating repeated categorical variables of litter size.ResultsFour SNPs on chromosomes 2, 20 and 21 were identified to be significantly associated (FDR p < 0.05) with LSB after multiple testing correction under a Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model. Least-square analysis was performed to investigate the effects of detected genotypes on LSB. Ultimately, the GWAS results introduced six candidate genes, including GABRA5, AKAP13, SV2B, PPP1R1C, SSFA2 and TRNAS-GCU in a 100 kb adjacent region of the identified SNPs. Previous studies proposed functional roles of GABRA5 and AKAP13 genes in reproductive processes; however, the role of other candidate genes in reproduction is not clear.ConclusionThese findings warrant further investigation for use in marker-assisted selection programs in Markhoz goats.

Simple Summary This study investigated the effects of pain relief treatments on behaviour and weight gain in 92 Nellore and crossbred (F1 Aberdeen Angus x Nellore) heifer calves (aged around 120 days) subjected to hot-iron branding on the cheek after vaccination against brucellosis. Four treatments were compared: Control (CO, no pain relief); local anaesthesia (LA, subcutaneous anaesthetic); analgesic (LT, intramuscular meloxicam); and local anaesthetic and analgesic (LL, both local anaesthesia and meloxicam). Calves in treatments CO and LT were subjected to face manipulation simulating application of local anaesthetic without introducing the needle. Facial and body expressions, flight speed, and body weight were recorded before, during, and five (5-d) and 60 days (60-d) after hot-iron branding. No effect of pain relief was observed for most calves studied. The only difference observed was higher tension ('tense') at 5-d in CO calves. All calves showed fear and stress responses during restraint and hot-iron branding, which probably masked pain responses. In conclusion, hot-iron facial branding impoverishes calf welfare and, due to the additional handling involved, adoption of a pain relief protocol is not an efficient way to minimise welfare impacts. Hot-iron branding is still commonly performed in cattle farming in tropical countries, and possibly has negative consequences for animal welfare and weight gain. This study examined the behavioural and weight gain responses of pure and crossbred Nellore heifer calves subjected to hot-iron branding on the cheek, without and with use of anaesthesia and analgesia. Ninety-two heifer calves, around 120 days old, were studied prospectively when subjected to hot-iron branding on the cheek (a statutory procedure in Brazil following brucellosis vaccination). Four randomly selected groups of calves were allocated to four treatments: no pain control (CO); subcutaneous anaesthetic local block (LA); intramuscular analgesia (meloxicam) (LT); and local anaesthesia plus meloxicam (LL). Behaviour, flight speed and body weight were evaluated before, during, and five (5-d) and 60 days (60-d) after branding. For these parameters, the only difference observed was higher tension in the CO group 5-d post-branding, suggesting a short-term negative effect of branding without pain control. The limited effects of the pain control treatments suggest interference in pain assessment by other factors, such as expression of fear and stress. Despite the lack of differences observed in behaviour and production parameters, facial hot-iron branding is an obvious welfare issue and, due to the additional handling involved, adoption of a simple pain relief protocol is not sufficient to minimise the welfare impact.

Streptococcus equi subsp. equi ( S. equi) is transmitted via contact with infected horses or fomites such as equipment or surfaces of the stable environment. Effective cleaning and sanitation is essential to mini-mize risk of fomite-associated infections. This study assessed the effectiveness of cleaning and sanitation of experimentally S. equi contaminated materials and equipment found in stables. Wood, concrete, plas-tic, leather halters, leather gloves and polyester webbing halters were inoculated with a 24-hour culture S. equi laboratory strain. In addition, selected materials were inoculated with a clinical strain of S. equi. Three days post inoculation all materials were sampled for retention of viable S. equi and a subset of each material was cleaned and sanitized. After an additional 2 days all treated and untreated materials were sampled for continued retention of viable S. equi. Separate subsets of contaminated polyester halter material were washed at 40 degrees C with or without drying at 70 degrees C, or washed at 60 degrees C. After cleaning and sanitation, all samples except polyester halters were culture negative. Even before cleaning and sanita-tion leather appears to poorly support survival of S. equi. After washing at 40 degrees C and tumble drying, 14 of 16 halters were culture positive, however culture negative when washed at 60 degrees C. Routine cleaning and sanitation of fomites contaminated with S. equi was generally effective to eliminate viable bacteria. How-ever, survival between materials and strains differed, with leather poorly permissive to S. equi survival even without cleaning, whereas polyester webbing halters retained viable S. equi even after washing at temperatures of 40 degrees C.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Background Leptospirosis is an emerging zoonotic infection worldwide and a cause of life-threatening disease in dogs. Seroprevalence in Swedish dogs is unknown. The aims of the present study were to estimate seroprevalence of pathogenic Leptospira in healthy dogs in Sweden using the microagglutination test (MAT) and a rapid point-of-care enzyme-linked immunosorbent assay (ELISA), and to evaluate risk factors of Leptospira exposure in Swedish dogs. Results Positive MAT titres (≥ 1:50) were detected in 27/369 (7.3%) of included dogs. Five different serovars were represented of which the Saxkoebing serovar was the most common (64.3%), followed by Copenhagi (14.3%), Bratislava (10.7%), Icterohaemorrhagiae (7.1%), and Canicola (3.6%). The ELISA test (SNAP® Lepto) was positive in 3/316 (0.9%) dogs. Living in urban areas and contact with stagnant water were found to be risk factors for Leptospira seropositivity (p Conclusion In this first seroprevalence study of Leptospira in Swedish dogs, it was shown that healthy dogs without recent (24 months) travel history and antileptospira vaccination had been exposed to pathogenic Leptospira interrogans serovars. Contact with stagnant water and living in urban areas were independent risk factors for seropositivity.

Background Good reproductive performance is fundamental for the development of a breed. Previous studies have indicated that the Bernese mountain dog has a relatively high prevalence of reproductive problems such as a high prevalence of dystocia and a low mean litter size. When reproduction is impaired, selection for other traits, including improved health, will become more difficult. The aim of this study was therefore to evaluate reproductive data and factors affecting these in the Bernese mountain dog. Data collected by the Swedish Sennenhund Club during the years 2010–2020 were evaluated by statistical analyses. Results Information from 1287 reported matings were included with a total of 614 bitches and 399 sires. For five reported matings that did not result in a litter, there was no information about the male identity. The reported matings resulted in 798 litters (62% whelping rate) from 502 bitches and 314 males. Paternal and maternal age had a significant effect on whelping rate with a negative effect of increasing age (P Conclusions Parity and maternal age had opposite effects on reproductive outcomes with a positive effect of parity on increasing litter size and decreasing CS rate. The proportion of unsuccessful matings was high with a negative effect of increasing age of both males and females.

Background Cerebellar abiotrophy (CA) is an uncommon hereditary neurodegenerative disorder affecting the cerebellar Purkinje cells. Equine CA has been reported in several breeds, but a genetic etiology has only been confirmed in the Arabian breed, where CA is caused by an autosomal recessive mutation. Case presentation. Clinical and histological findings consistent with CA are reported in an 8.5-month-old Icelandic filly. The filly showed a perceived sudden onset of marked head tremor, incoordination, ataxia, lack of menace response and a broad-based stance. Cerebrospinal fluid, hematological and biochemical findings were all within the normal range, ruling out several differential diagnoses. Post mortem histopathological examination revealed Purkinje cell degeneration accompanied by astrogliosis. Assessment of the filly’s pedigree revealed that its parents shared a common ancestor. Conclusions To the authors’ knowledge, this is the first report of CA in the Icelandic breed. The identification of a common parental ancestor makes autosomal recessive inheritance of CA in this filly possible, but this would need to be confirmed by further studies. Veterinarians and breeders working with Icelandic horses should be aware of this condition and report suspected cases in order to support genetic investigation.

International audience; Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission.

Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.

Objectives The aims of this study were to assess the potential associations between the serum cardiac troponin I (cTnI) concentration in healthy cats and feline characteristics, systolic blood pressure, heart rate (HR), echocardiographic measurements and storage time; and to compare cTnI concentrations in healthy cats with concentrations in cats with hypertrophic cardiomyopathy (HCM), with or without left atrial enlargement (LAE) and in cats with HCM, to assess potential associations between cTnI concentration and echocardiographic variables. Methods Cardiac TnI was analysed using an Abbott ARCHITECT ci16200 analyser in serum from prospectively included healthy Norwegian Forest Cat (NF; n = 33), Birman (n = 33) and domestic shorthair (DSH; n = 30) cats, and from 39 cats with HCM, with or without LAE. Results In healthy cats, higher cTnI concentrations were found in Birman cats than in NF cats ( P = 0.014) and in neutered male cats than in intact females ( P = 0.032). Cardiac TnI was positively associated with HR ( P Conclusions and relevance Breed and sex may affect serum cTnI concentrations in healthy cats. The cTnI concentration increased with increasing severity of HCM.