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"Brachycephaly" is generally considered a phenotype in which the facial part of the head is pronouncedly shortened. While brachycephaly is characteristic for some domestic varieties and breeds (e.g., Bulldog, Persian cat, Niata cattle, Anglo-Nubian goat, Middle White pig), this phenotype can also be considered pathological. Despite the superficially similar appearance of "brachycephaly" in such varieties and breeds, closer examination reveals that "brachycephaly" includes a variety of different cranial modifications with likely different genetic and developmental underpinnings and related with specific breed histories. We review the various definitions and characteristics associated with brachycephaly in different domesticated species. We discern different types of brachycephaly ("bulldog-type," "katantognathic," and "allometric" brachycephaly) and discuss morphological conditions related to brachycephaly, including diseases (e.g., brachycephalic airway obstructive syndrome). Further, we examine the complex underlying genetic and developmental processes and the culturally and developmentally related reasons why brachycephalic varieties may or may not be prevalent in certain domesticated species. Knowledge on patterns and mechanisms associated with brachycephaly is relevant for domestication research, veterinary and human medicine, as well as evolutionary biology, and highlights the profound influence of artificial selection by humans on animal morphology, evolution, and welfare.

Objective. To evaluate both factors predicting nontransport and mortality rates in an emergency medical services system with a nontransport policy. Methods. We reviewed data from 1,581 transported and nontransported patients from October 2001 to July 2003. Patients who refused transport against medical advice were excluded. Extracted data included demographics, run characteristics, chief complaint, and clinical impression. Transported and nontransported patients were compared using Mann-Whitney U or chi-square tests. Logistic regression identified factors predictive of nontransport. A Social Security Death Index search determined 30-day mortality. Results. A total of 1,501 runs involving 1,059 patients were included. Median age was 60 years (range, 0-97 years). A total of 427 (40.4%) were male; 107 (10.2%) were nonwhite. Older patients were more likely to be transported (odds ratio, 1.03; confidence interval, 1.02-1.03). Race, frequency of calls, mutual aid, or time of day did not significantly influence probability of transport. Patients with cardiovascular, respiratory, and gastrointestinal complaints were more likely to be transported than those with other conditions (P < 0.005); patients with endocrine, trauma, and miscellaneous complaints were less likely to be transported (P < 0.003). Patients with renal, obstetrics/gynecology, and hema matology/oncology were complaints all transported. Mortality was 4.9% (confidence interval, 3.9%-6.2%) for transported patients and 1.0% for those not transported (confidence interval, 0.2%-3.7%). Conclusions. Age is a determinant when deciding on transporting patients. Patients with complaints with potentially higher acuity were transported most often. Only two nontransported patients died within 30 days, although it is unknown whether initial transport would have changed their mortality. Our data suggest that emergency medical services-initiated nontransport is influenced only by age and chief complaint and may not result in significant mortality. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined whether serum carnitine and dehydro-epiandrosterone sulphate levels in healthy adult men and women may account for the declining energy metabolism associated with age. Background to the study; Methods; Results; Conclusion.

Our research aims to understand the adaptive, ergo potentially metastatic, responses of prostate cancer to changing microenvironments. Emerging evidence implicates a role of the Polyaneuploid Cancer Cell (PACC) state in metastasis, positing the PACC state as capable of conferring metastatic competency. Mounting in vitro evidence supports increased metastatic potential of cells in the PACC state. Additionally, our recent retrospective study revealed that PACC presence in patient prostate tumors at the time of radical prostatectomy was predictive of future metastasis. To test for a causative relationship between PACC state biology and metastasis in prostate cancer, we leveraged a novel method designed for flow-cytometric detection of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) from animal models. This approach provides both quantitative and qualitative information about the number and PACC-status of recovered CTCs and DTCs. Specifically, we applied this approach to analysis of subcutaneous, caudal artery, and intracardiac murine models. Collating data from all models, we found that 74% of recovered CTCs and DTCs were in the PACC state. Furthermore, in vivo colonization assays proved PACC populations can regain proliferative capacity at metastatic sites. Additional in vitro analyses revealed a PACC-specific partial Epithelial-to-Mesenchymal-Transition phenotype and a pro-metastatic secretory profile, together providing preliminary evidence of pro-metastatic mechanisms specific to the PACC state. Implications: Considering that many anti-cancer agents induce the PACC state, our data positions the increased metastatic competency of PACC state cells as an important unforeseen ramification of neoadjuvant regimens, which may help explain clinical correlations between chemotherapy and metastatic progression.

Background: Heterogeneity can impact biomarker identification. Thus, we investigated the somatic copy number alterations (SCNAs) of individual tumor cells in the vitreous humor of a retinoblastoma patient using single-cell whole-genome profiling and explored the genomic concordance among vitreous and aqueous humor, vitreous seeds, and tumor., Methods: Aqueous humor (AH), vitreous humor (VH), and tumor biopsy were obtained from an enucleated globe with retinoblastoma and vitreous seeding. Micromanipulation was used to manually isolate 39 live single tumor cells from vitreous seeds harvested from the VH. The SCNA profiles of these individual cells were generated via whole-genome sequencing and analyzed alongside profiles from the tumor mass and cell-free DNA (cfDNA) from AH and VH., Results: Heatmap of VH single-cell SCNA profiles demonstrates heterogeneity among individual vitreous seeds with one clearly dominant subclone (23 of 37 cells). The SCNA profiles from the cells in this subclone demonstrate an average concordance of 98% with cfDNA profiles from acellular AH and VH and with the tumor profile., Conclusions: Our findings reveal some heterogeneity among single-cell SCNA profiles in individual VH seeds. Despite this heterogeneity, the dominant vitreous subclone exhibits extremely (>98%) high concordance with the SCNA profile from tumor and AH, suggesting AH cfDNA is representative of the dominant genomic subclone. This may facilitate tumoral biomarker identification via the AH. This preliminary work supports the potential of applying single-cell technology to VH seeds in retinoblastoma as a platform to study tumor subclones, which may provide insight into the genomic complexity of disease.

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression-free survival. Single cell copy number profiling of CTC-IGC displayed clonal origins with typical CTCs, suggesting complete polyploidization. Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. Novel RNA and protein markers, including HOMER1, TNFRSF9, and LRP1, were identified as linked to chemotherapy resistance. These markers were also present in a subset of patient CTCs and are associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and the expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development., Competing Interests: Competing interests: The HDSCA technology described here is licensed to Epic Sciences. PK has ownership in Epic Sciences. JH discloses he is a member of the Clinical Advisory Board of Epic Sciences. KJP is a consultant for CUE Biopharma, Inc., and holds equity interest in CUE Biopharma, Inc., Keystone Biopharma, Inc., PEEL Therapeutics, Inc and Kreftect, Inc. SRA holds equity interest in Keystone Biopharma, Inc. Ethics Approval and Consent to Participate: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of the University of Southern California Keck School of Medicine, MD Anderson (NCT01505868), and the VA of Los Angeles (PCC 2015-090980). Informed consent was obtained from all subjects involved in the study. Consent for Publication: All the authors agree to publish this paper., (© 2024. The Author(s).)

Background: Brachycephalic dogs are overrepresented with ventricular enlargement. Cerebrospinal fluid (CSF) flow dynamics are not completely understood. MRI techniques have been used for the visualization of CSF dynamics including phase-contrast imaging., Objectives: This study aimed to determine a causality between CSF flow and ventriculomegaly or hydrocephalus and to compare CSF flow dynamics among dogs with ventriculomegaly, internal hydrocephalus, and physiologic ventricles., Animals: A total of 51 client-owned dogs were included in the study., Methods: Magnetic resonance imaging (MRI)-based FLASH sequences and phase-contrast images of the brain were obtained, and the ROI was placed at the level of the mesencephalic aqueduct. ECG monitoring was performed parallel to MRI acquisition. Evaluation of flow diagrams and processing of phase-contrast images were performed using commercially available software (Argus VA80A, Siemens AG Healthcare Sector, Erlangen, Germany). Dogs were divided into three groups: Group 1 consisted of brachycephalic dogs with ventriculomegaly (group 1A) or internal hydrocephalus (group 1B), group 2 consisted of brachycephalic dogs with normal ventricles, and group 3 consisted of meso- to dolichocephalic dogs with normal ventricles., Results: Group 1 had a higher median V rost (4.32 cm/s; CI: 2.94-6.33 cm/s) and V caud (-6.1 cm/s, CI: 3.99-9.33 cm/s) than group 2 (V rost : 1.99 cm/s; CI 1.43-2.78 cm/s; V caud: 2.91 cm/s, CI: 2.01-4.21 cm/s; p  = 0.008; p  = 0.03) and group 3 (V rost :1.85 cm/s, CI: 1.31-2.60 cm/s; V caud  - 2.46 cm/s, CI 1.68-3.58 cm/s; p  = 0.01; p  = 0.02). The median Vol caud of group 1 (-0.23 mL/min, CI: 0.13-0.42 mL/min) was higher than that of group 2 (-0.09 mL/min, CI: 0.05 mL/min and 0.15 mL/min) ( p  = 0.03). Groups 1A and 1B did not differ in V caud , V rost , Vol caud , and Vol rost . Group 1A and 1B showed a higher median V rost (4.01 cm/s, CI: 2.30-7.05 cm/s; 5.94 cm/s, CI: 2.16-7.88 cm/s) than group 2 (1.85 cm/s, CI: 1.24-2.80 cm/s.) ( p  = 0.03; p  = 0.004)., Conclusion and Clinical Importance: Increased CSF flow velocities in rostral and caudal directions are present in dogs with ventriculomegaly and internal hydrocephalus compared to normal controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Farke, Dörn, Schaub, Wenz, Büttner and Schmidt.)

Background: Dogs with internal hydrocephalus do not necessarily have high intraventricular pressure (IVP)., Hypothesis/objectives: Not all reported MRI findings indicate high IVP and some clinical signs might be associated with elevated IVP and syringomyelia., Animals: Fifty-three dogs., Materials and Methods: Cross-sectional study. Clinical signs and MRI findings were evaluated for an association of IVP >12 mm Hg and syringomyelia., Results: High IVP was associated with obtundation OR 4.64 (95% CI 1.27-16.93) (P = .02), head tilt OR 6.42 (95% CI 1.08-37.97) (P = .04) and nystagmus OR 8.24 (95% CI 1.44-47.07) (P = .02). Pain was associated with syringomyelia OR 3.4 (95% CI 0.98-11.78) (P = .05). The number of affected ventricles was associated with high IVP OR 2.85 (95% CI 0.97-8.33) (P = .05) and syringomyelia OR 12.74 (95% CI 2.93-55.4) (P = .0007). Periventricular edema OR 24.46 (95% CI 4.54-131.77), OR 7.61 (95% CI 1.91-30.32) (P < .0002, P = .004) and signal void sign OR 17.34 (95% CI 4.01-74.95), OR 4.18 (95% CI 1.16-15.02) (P < .0001, P = .03) were associated with high IVP and syringomyelia. The probability for syringomyelia is lower with disruption of the internal capsule OR 0.19 (95% CI 0.05-0.72) (P = .01) and higher VBR OR 0.25 (95% CI 0.1-0.63) (P = .004)., Conclusions and Clinical Importance: Previously reported MRI findings are not predictive of high IVP. Clinical signs and MRI findings should be used to make a diagnosis of internal hydrocephalus in dogs with or without high IVP., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

This study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from 2 different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some individuals exhibiting signs of deafness, and 8 stillborn kittens. Samples from the Topaz lineage included 10 blue-eyed animals. A brainstem auditory evoked response test revealed a reduced to absent response to auditory stimuli and absent physiological waveforms in all of the 8 examined DBE animals. We sequenced the genome of 2 affected cats from the Dutch line and searched for variants in 19 candidate genes for the human Waardenburg syndrome and pigmentary disorders. This search yielded 9 private protein-changing candidate variants in the genes PAX3, EDN3, KIT, OCA2, SLC24A5, HERC2, and TYRP1. The genotype-phenotype cosegregation was observed for the PAX3 variant within all animals from the Dutch lineage. The mutant allele was absent from 461 control genomes and 241 additionally genotyped green-eyed Maine Coons. We considered the PAX3 variant as the most plausible candidate-a heterozygous nonsense single base pair substitution in exon 6 of PAX3 (NC&#95;051841.1:g.205,787,310G>A, XM&#95;019838731.3:c.937C>T, XP&#95;019694290.1:p.Gln313*), predicted to result in a premature stop codon. PAX3 variants cause auditory-pigmentary syndrome in humans, horses, and mice. Together with the comparative data from other species, our findings strongly suggest PAX3:c.937C>T (OMIA:001688-9685) as the most likely candidate variant for the DBE, deafness, and minimal white spotting in the Maine Coon Dutch line. Finally, we propose the designation of DBERE (Rociri Elvis Dominant Blue Eyes) allele in the domestic cat., Competing Interests: Conflicts of interest GRG and KS are affiliated with commercial laboratories offering genetic testing for domestic animals. The other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Ventriculoperitoneal shunt placement is an effective method to treat internal hydrocephalus in dogs and cats. Although it has a long history in veterinary medicine, the technique continues to evolve. Despite continuing attempts to reduce the incidence of associated complications, shunt failure remains a major problem, and often leads to multiple hospital admissions. This review gives an overview about current knowledge of ventriculoperitoneal shunting techniques in animals, applicable shunt hardware as well as shunt-associated complications and their prevention and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schmidt and Farke.)

Burnout syndrome is characterized by exhaustion, cynicism, and reduced effectiveness. Workers with high burnout scores who continue their professional activities are identified as experiencing non-clinical burnout (NCB), which includes early stages where burnout symptoms (BNS) are present but not yet severe enough to necessitate work leave. This study aimed to investigate the impact of BNS on attention performance among healthcare workers (HCWs) at a COVID-19 reference hospital during the pandemic. The Maslach Burnout Inventory (MBI) was applied to assess the three burnout dimensions. The Continuous Visual Attention Test (CVAT) evaluated four different attention subdomains. Participants were divided into two groups based on their scores on the MBI: controls and NCB. Thirteen controls were matched with 13 NCB subjects based on age, sex, and HCW category. This sample ( n = 26, 65% male) consisted of 11 physicians and 15 nursing professionals with a mean age of 35.3 years (standard deviation = 5.47). NCB subjects had higher impulsivity than controls. There were not any significant group differences in the other attention subdomains. We found significant correlations between impulsivity and all burnout dimensions: higher absolute scores in BNS are associated with higher impulsivity. We concluded that NCB leads to executive attention deficits.

Microcephaly is a rare neurodevelopmental disorder characterized by reduced skull circumference and brain volume that occurs sporadically in farm animals. We investigated an early-onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly. The pedigree of the lambs suggested monogenic autosomal recessive inheritance. We sequenced the genome of one affected lamb, and comparison with 115 control genomes revealed a single private protein-changing variant. This frameshift variant, MFSD2A: c.285dupA, p.(Asp96fs*9), represents a 1-bp duplication predicted to truncate 80% of the open reading frame. MFSD2A is a transmembrane protein that is essential for maintaining blood-brain barrier homeostasis and plays a key role in regulating brain lipogenesis. Human MFSD2A pathogenic variants are associated with a neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA, OMIM 616486). Here we present evidence for the occurrence of a recessively inherited form of microcephaly in sheep due to a loss-of-function variant in MFSD2A (OMIA 002371-9940). To the best of our knowledge, this is the first report of a spontaneous MFSD2A variant in domestic animals., (© 2023 Stichting International Foundation for Animal Genetics.)

Introduction: Internal hydrocephalus is the most common malformation of the central nervous system in dogs. Although the grades of ventricular distension have importance for long-term prognosis, there is no standard classification scheme describing the grade of the ventricular distension in dogs., Materials and Methods: Magnetic resonance imaging (MRI) scans from 147 dogs of various breed, sex, skull conformation, and weight were reviewed retrospectively and blinded between three observers. Based on objectively assessable morphologic characteristics, the lateral cerebral ventricles were graded as normal, minimally, mildly, moderately, severely enlarged or end stage (grade 0 to grade 5), respectively. Evans' index or the ventricle brain index was also measured in all animals. Interobserver agreement between a very experienced, experienced, and unexperienced person was evaluated by the Spearman coefficient and kappa tests. Additionally, correlation to the ventricle brain index was determined using the Spearman coefficient and F-tests., Results: The Spearman correlation coefficient reached a very strong correlation ( r = 0.97) between the experienced and very experienced observer and a strong correlation ( r = 0.91) between the very experienced and unexperienced observer. The kappa value revealed excellent interobserver agreement between the very experienced and experienced observers (weighted kappa 0.91) and moderate between the very experienced and unexperienced observers (weighted kappa 0.75). The ventricular-brain index correlated ( r = 0.94, Spearman coefficient test) with the grading system, indicating that a more elevated ratio was related to a more advanced degree of ventricular enlargement. The interobserver agreement with regard to the grade between the neurologist in training and a board-certified neurologist was excellent and between the board-certified neurologist and general practitioner achieved lower values., Conclusion: The presented MRI-based grading of ventricular enlargement is a reliable and functional method for an objective grading of the ventricular system in dogs. Some experience in MRI and brain anatomy is needed for interpretation and grading., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor AT declared a past co-authorship with the author MS., (Copyright © 2023 Czerwik, Schmidt, Olszewska, Hinz, Büttner and Farke.)

Background: Overshunting and hemispheric collapse are well-known complications after ventriculoperitoneal shunt (VPS) implantation. Risk factors that predispose to overshunting, treatment options, and prognosis after therapeutic intervention have not been described., Hypothesis/objectives: To identify preoperative risk factors for overshunting, the effect of surgical decompression, and their outcomes., Animals: Seventy-five dogs and 7 cats., Methods: Retrospective case cohort study. Age, breed, sex, body weight, number of dilated ventricles, ventricle brain ratio, intraventricular pressure, and implanted pressure valve systems were evaluated as possible risk factors., Results: Overshunting had a prevalence of 18% (Cl 95% 9.9-26.66). An increase of 0.05 in VBR increased the risk of overshunting by OR 2.23 (Cl 95% 1.4-3.5; P = .001). Biventricular hydrocephalus had the highest risk for overshunting compared to a tri- (OR 2.48 with Cl 95% 0.5-11.1) or tetraventricular hydrocephalus (OR 11.6 with Cl 95% 1.7-81.1; P = .05). There was no influence regarding the use of gravitational vs differential pressure valves (P > .78). Overshunting resulted in hemispheric collapse, subdural hemorrhage, and peracute deterioration of neurological status in 15 animals. Subdural hematoma was removed in 8 dogs and 2 cats with prompt postoperative improvement of clinical signs., Conclusions and Clinical Importance: Biventricular hydrocephalus and increased VBR indicate a higher risk for overshunting. The use of differential valves with gravitational units has no influence on occurrence of overshunting related complications and outcomes. Decompressive surgery provides a favorable treatment option for hemispheric collapse and has a good outcome., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Fertile soil known as Amazonian dark earth is central to the debate over the size and ecological impact of ancient human populations in the Amazon. Dark earth is typically associated with human occupation, but it is uncertain whether it was created intentionally. Dark earth may also be a substantial carbon sink, but its spatial extent and carbon inventory are unknown. We demonstrate spatial and compositional similarities between ancient and modern dark earth and document modern Indigenous practices that enrich soil, which we use to propose a model for the formation of ancient dark earth. This comparison suggests that ancient Amazonians managed soil to improve fertility and increase crop productivity. These practices also sequestered and stored carbon in the soil for centuries, and we show that some ancient sites contain as much carbon as the above-ground rainforest biomass. Our results demonstrate the intentional creation of dark earth and highlight the value of Indigenous knowledge for sustainable rainforest management.

Introduction: Type A Aortic Dissection (TAAD) is a surgical emergency with a time-dependent rate of mortality. We hypothesized that a direct-to-operating room (DOR) transfer program for patients with TAAD would reduce time to intervention., Methods: A DOR program was started at an urban tertiary care hospital in February 2020. We performed a retrospective study of adult patients undergoing treatment for TAAD before (n = 42) and after (n = 84) implementation of DOR. Expected mortality was calculated using the International Registry of Acute Aortic Dissection risk prediction model., Results: Median time from acceptance of transfer from emergency physician to operating room arrival was 1.37 h (82 min) faster in DOR compared to pre-DOR (1.93 h vs 3.30 h, p < 0.001). Median time from arrival to operating room was 1.14 h (72 min) faster after DOR compared to pre-DOR (0.17 h vs 1.31 h, p < 0.001). In-hospital mortality was 16.2% in pre-DOR, with an observed-to-expected (O/E) ratio of 1.03 (p = 0.24) and 12.0% in the DOR group, with an O/E ratio of 0.59 (p < 0.001)., Conclusion: Creation of a DOR program resulted in decreased time to intervention. This was associated with a decrease in observed-to-expected operative mortality. The transfer of patients with acute type A aortic dissection to centers with direct-to-OR programs may result in decreased time from diagnosis to surgery., Competing Interests: Declaration of Competing Interest Christopher K. Mehta, MD: Gore: Speaker and Educational Funding. Duc Thinh Pham, MD: Abbott, Medtronic, Abiomed: Speaker and Advisory Panel. Douglas R. Johnston, MD: Advisor: Abbott, Edwards Lifesciences, Terumo, Livanova, HD Medical. S. Chris Malaisrie, MD: Edwards Lifesciences: Consultant; Medtronic, CryoLife, Atricure, Terumo Aortic: Consultant and Speaker. All other authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Pathomorphological alterations of the central nervous system in dogs, such as syringomyelia and Chiari-like malformation, can cause cranial and cervical hyperesthesia and neuropathic pain. The long-term activity of the pain network can induce functional alteration and eventually even morphological changes in the pain network. This may happen especially in the prefrontal and cingulate cortex, where atrophy of the gray matter (GM) was observed in humans with chronic pain, irrespective of the nature of the pain syndrome. We tested the hypothesis that Cavalier King Charles Spaniels (CKCS) with Chiari-like malformation and associated syringomyelia (SM) and pain show cerebral morphological differences compared to animals without signs of syringomyelia and pain., Methods: Volumetric datasets of 28 different brain structures were analyzed in a retrospective manner, including voxel-based morphometry, using magnetic resonance imaging data obtained from 41 dogs., Results: Volumetric analyses revealed a decrease in GM volumes in the cingulate gyrus (CG) in CKCS with SM and chronic pain when normalized to brain volume. This finding was supported by voxel-based morphometry, which showed a cluster of significance within the CG., Conclusion: GM atrophy in the CG is associated with chronic pain and thus may serve as an objective readout parameter for the diagnosis or treatment of canine pain syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nitzsche, Schulze, Boltze and Schmidt.)

Retinoblastoma (RB) is a childhood cancer that forms in the developing retina of young children; this tumor cannot be biopsied due to the risk of provoking extraocular tumor spread, which dramatically alters the treatment and survival of the patient. Recently, aqueous humor (AH), the clear fluid in the anterior chamber of the eye, has been developed as an organ-specific liquid biopsy for investigation of in vivo tumor-derived information found in the cell-free DNA (cfDNA) of the biofluid. However, identifying somatic genomic alterations, including both somatic copy number alterations (SCNAs) and single nucleotide variations (SNVs) of the RB1 gene, typically requires either: (1) two distinct experimental protocols-low-pass whole genome sequencing for SCNAs and targeted sequencing for SNVs-or (2) expensive deep whole genome or exome sequencing. To save time and cost, we applied a one-step targeted sequencing method to identify both SCNAs and RB1 SNVs in children with RB. High concordance (median = 96.2%) was observed in comparing SCNA calls derived from targeted sequencing to the traditional low-pass whole genome sequencing method. We further applied this method to investigate the degree of concordance of genomic alterations between paired tumor and AH samples from 11 RB eyes. We found 11/11 AH samples (100%) had SCNAs, and 10 of them (90.1%) with recurrent RB-SCNAs, while only nine out of 11 tumor samples (81.8%) had positive RB-SCNA signatures in both low-pass and targeted methods. Eight out of the nine (88.9%) detected SNVs were shared between AH and tumor samples. Ultimately, 11/11 cases have somatic alterations identified, including nine RB1 SNVs and 10 recurrent RB-SCNAs with four focal RB1 deletions and one MYCN gain. The results presented show the feasibility of utilizing one sequencing approach to obtain SCNA and targeted SNV data to capture a broad genomic scope of RB disease, which may ultimately expedite clinical intervention and be less expensive than other methods.

Our knowledge about the underlying pathomechanisms of craniocervical junction abnormalities (CCJA) in dogs mostly derives from measurements based on tomographic imaging. These images are static and the positioning of the dogs' head does not reflect the physiological in vivo position of the craniocervical junction (CCJ). Aberrant motion patterns and ranges of motion (ROM) in sound individuals of CCJA predisposed breeds may be a pathogenetic trigger. To further extend our limited knowledge of physiological motion of the CCJ, this prospective, comparative study investigates the in vivo motion patterns and ROM of the CCJ in walk and trot in sound Cavalier King Charles Spaniels and Chihuahuas. The Labrador retriever is used as a reference breed without predisposition for CCJA. This is the first detailed description of CCJ movement of trotting dogs. Biplanar fluoroscopy images, recorded in walking and trotting dogs, were matched to a virtual reconstruction of the skull and cranial cervical spine utilising Scientific Rotoscoping. Kinematic data reveal the same motion patterns among all breeds and gaits with individual temporal and spatial differences in each dog. A stride cycle-dependent lateral rotation of the cranial cervical spine and axial rotation of the atlantoaxial joint in trot in dogs is described for the first time. The ROM of the atlantoaxial and atlantooccipital joints in walk and trot were not statistically significantly greater in the CCJA-predisposed breeds CKCS and Chihuahua. ROM values of all translational and rotational degrees of freedom were larger in walk than trot, although this is only statistically significant for the atlantoaxial joint. Until proven otherwise, a more species-specific than breed-specific general motion pattern of the CCJ in walking and trotting, clinically sound dogs must be assumed. Species-specific anatomic properties of the CCJ seem to supersede breed-specific anatomical differences in clinically sound dogs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nickel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Gabapentin and pregabalin are drugs to treat neuropathic pain. Several studies highlighted effects on presynaptic terminals of nociceptors. Via binding to α2δ subunits of voltage-gated calcium channels, gabapentinoids modulate the synaptic transmission of nociceptive information. However, recent studies revealed further properties of these substances. Treatment with gabapentin or pregabalin in animal models of neuropathic pain resulted not only in reduced symptoms of hyperalgesia but also in an attenuated activation of glial cells and decreased production of pro-inflammatory mediators in the spinal dorsal horn., Methods: In the present study, we aimed to investigate the impact of gabapentinoids on the inflammatory response of spinal dorsal horn cells, applying the established model of neuro-glial primary cell cultures of the superficial dorsal horn (SDH). We studied effects of gabapentin and pregabalin on lipopolysaccharide (LPS)-induced cytokine release (bioassays), expression of inflammatory marker genes (RT-qPCR), activation of transcription factors (immunocytochemistry), and Ca2+ responses of SDH neurons to stimulation with substance P and glutamate (Ca2+-imaging)., Results: We detected an attenuated LPS-induced expression and release of interleukin-6 by SDH cultures in the presence of gabapentinoids. In addition, a significant main effect of drug treatment was observed for mRNA expression of microsomal prostaglandin E synthase 1 and the inhibitor of nuclear factor kappa B. Nuclear translocation of inflammatory transcription factors in glial cells was not significantly affected by gabapentinoid treatment. Moreover, both substances did not modulate neuronal responses upon stimulation with substance P or glutamate., Conclusion: Our results provide evidence for anti-inflammatory capacities of gabapentinoids on the acute inflammatory response of SDH primary cultures upon LPS stimulation. Such effects may contribute to the pain-relieving effects of gabapentinoids., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

In recent years there has been increased attention to the proposed entity of feline temporal lobe epilepsy (TLE). Epileptic discharges in certain parts of the temporal lobe elicit very similar semiology, which justifies grouping these epilepsies under one name. Furthermore, feline TLE patients tend to have histopathological changes within the temporal lobe, usually in the hippocampus. The initial aetiology is likely to be different but may result in hippocampal necrosis and later hippocampal sclerosis. The aim of this article was not only to summarise the clinical features and the possible aetiology, but also being work to place TLE within the veterinary epilepsy classification. Epilepsies in cats, similar to dogs, are classified based on the aetiology into idiopathic epilepsy, structural epilepsy and unknown cause. TLE seems to be outside of this classification, as it is not an aetiologic category, but a syndrome, associated with a topographic affiliation to a certain anatomical brain structure. Magnetic resonance imaging, histopathologic aspects and current medical therapeutic considerations will be summarised, and emerging surgical options are discussed., Competing Interests: Conflict of interest statement None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Universities are vulnerable to infectious disease outbreaks, making them ideal environments to study transmission dynamics and evaluate mitigation and surveillance measures. Here, we analyze multimodal COVID-19-associated data collected during the 2020-2021 academic year at Colorado Mesa University and introduce a SARS-CoV-2 surveillance and response framework., Methods: We analyzed epidemiological and sociobehavioral data (demographics, contact tracing, and WiFi-based co-location data) alongside pathogen surveillance data (wastewater and diagnostic testing, and viral genomic sequencing of wastewater and clinical specimens) to characterize outbreak dynamics and inform policy. We applied relative risk, multiple linear regression, and social network assortativity to identify attributes or behaviors associated with contracting SARS-CoV-2. To characterize SARS-CoV-2 transmission, we used viral sequencing, phylogenomic tools, and functional assays., Findings: Athletes, particularly those on high-contact teams, had the highest risk of testing positive. On average, individuals who tested positive had more contacts and longer interaction durations than individuals who never tested positive. The distribution of contacts per individual was overdispersed, although not as overdispersed as the distribution of phylogenomic descendants. Corroboration via technical replicates was essential for identification of wastewater mutations., Conclusions: Based on our findings, we formulate a framework that combines tools into an integrated disease surveillance program that can be implemented in other congregate settings with limited resources., Funding: This work was supported by the National Science Foundation, the Hertz Foundation, the National Institutes of Health, the Centers for Disease Control and Prevention, the Massachusetts Consortium on Pathogen Readiness, the Howard Hughes Medical Institute, the Flu Lab, and the Audacious Project., Competing Interests: Declaration of interests P.C.S. is a co-founder of, shareholder in, and scientific advisor to Sherlock Biosciences, Inc.; she is also a Board member of and shareholder in Danaher Corporation. P.C.S. has filed IP related to genome sequencing and analysis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Virchow-Robin-Spaces (VRS) are cerebrospinal fluid (CSF)-containing perivascular spaces encompassing brain vessels while coursing through the parenchyma. VRS can enlarge and become visible in magnetic resonance imaging (MRI). While dilatated VRS are mostly incidental findings, they were associated with degenerative brain disease in humans. This study aimed to evaluate their occurrence and MRI morphology within the ventral forebrain of structurally normal canine and feline brains and physiological cerebrospinal fluid analysis., Sample: Retro- and prospective, observational study reviewing medical records of client-owned dogs and cats which underwent MRI brain scans for unrelated reasons between 2011 and 2021. We comprised studies with various magnetic field strengths (1 Tesla/3 Tesla). Out of 2500 brain scans, three hundred thirty-five patients (293 dogs, 42 cats) presented with absent intracranial pathology and physiological CSF analysis and were included., Procedure: The ventral forebrain of the included animals was assessed for bi- or unilateral CSF-isointense foci in the transverse plane. Statistical correlations were evaluated between dilated VRS presence, field strength, age, gender, weight, and cranium conformation. Additionally, a post-mortem histopathologic analysis of one dog and one cat showing dilated VRS on MRI was performed to confirm perforating arteries in the gray matter of the ventral forebrain., Results: 57% of patients presented dilated VRS ( N = 191: 170 dogs, 21 cats). 43% did not display dilated VRS (control group; N = 144: 123 dogs, 21 cats). A significant relation between increased magnetic field strength and detection of dilated VRS was observed in dogs; there was a 2.4 increase ( p = 0.0001) in detection using 3 Tesla vs. 1 Tesla. There was a 2.4-fold increase in dilated VRS occurrence in male dogs compared to female dogs. Detection also increased with the rise of body weight. We detected no statistically significant difference between dilated VRS and the control group in age, species or cranium conformation., Conclusion and Clinical Relevance: Dilated VRS can be seen within the ventral forebrain at the level of the rostral commissure on transverse MR images as symmetrical or unilateral, dot-like, CSF-isointense areas. Understanding their signal intensity features and localization prevents misinterpretation and helps differentiate them from various pathological conditions., Competing Interests: Author KH was employed by company VETCARE, Pferde- und Kleintierpraxis AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fischer, Schaub, Büttner, Hartmann and Schmidt.)

Purpose: To analyze the impact of the coronavirus disease (COVID) pandemic on emergency department (ED) computed tomography (CT) utilization., Methods: A retrospective observational study was conducted assessing seven hospitals' ED imaging volumes between Jan. 6, 2019, and Feb. 27, 2021. Weekly CT utilization is reported as CTs ordered per 100 ED visits. Utilization was ascertained in aggregate and by body area. Interrupted time series analysis was performed to assess significance of utilization change. Prespecified sensitivity analysis was performed for influenza-like or COVID-like illness (ILI/CLI)., Results: Weekly ED CT utilization increased from 35.9 CTs per 100 visits (95% confidence interval [95% CI] 35.8-36.1) to 41.8 per 100 visits (95% CI 41.7-42.0) in pre- and post-pandemic periods. Weekly ED CT chest utilization increased immediately following the pandemic declaration (+ 0.52 chest CTs per 100 ED visits, 95% CI 0.01-1.03, p < 0.05) and compared to pre-pandemic period (+ 0.02 per 100 ED visits, 95% CI 0.02-0.05, p < 0.02). For both CT abdomen/pelvis and CT head, there was neither an immediate effect (+ 0.34 CT-AP per 100 ED visits, 95% CI - 0.74 to 1.44, p = 0.89; - 0.42 CT-H per 100 ED visits, 95% CI - 1.53 to 0.70, p = 0.46) nor a change in weekly CT utilization (+ 0.03 CT-AP per 100 ED visits, 95% CI - 0.01 to 0.05, p = 0.09; + 0.03 CT-H per 100 ED visits, 95% CI - 0.01 to 0.06, p = 0.10).  CONCLUSION: These data may help formulate future strategies for resource utilization and imaging operations as we envision a future with COVID and other federal mandates affecting imaging utilization and appropriateness., (© 2022. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Objective:  The aim of this study was to evaluate differences in paraspinal musculature between dogs with and without atlantoaxial instability (AAI) using computed tomography scans., Study Design:  Retrospective multicentre study evaluating transverse reconstructed computed tomography scans of 83 small breed dogs (34 with and 49 without AAI) for the cross-sectional paraspinal musculature area at three levels (Occiput/C1, mid-C1, mid-C2). Ratio of moments, dorsal-to-ventral muscle-area ratios (d-v-ratio) and ratios of the dorsal and ventral musculature to C2 height (d-C2-ratio and v-C2-ratio) were evaluated for differences between groups using multivariate analysis of variance ( p  < 0.05) taking the head-neck position into account., Results:  Dogs with AAI showed a significantly lower d-v-ratio at levels 2 and 3, d-C2-ratio at level 2 and ratio of moments at all levels. When head-neck positions were analysed separately, ratio of moments was significantly lower in affected dogs at level 1 and 2. Also lower was d-C2-ratio at level 2, but only in flexed positioning. The head-neck position had a significant influence on ratio of moments and d-v-ratio at all three levels and on d-C2-ratio at level 1., Conclusion:  Significant changes in muscle area were observed only for the hypaxial muscles at the C1 level, indicating a limited role of muscular adaption in AAI patients. Our results confirm an altered ratio of moments in dogs with AAI. The head-neck position has a significant impact and should be taken into account when evaluating spinal musculature., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Compression of epidural adipose tissue (EAT) within the scope of cauda equina syndrome (CES) could lead to an enhanced expression of inflammatory mediators, possibly contributing to pain amplification in dogs., Objectives: To analyze expression of inflammatory adipo(-cyto)kines within the EAT of dogs with CES., Animals: Client-owned dogs: 15 dogs with CES and 9 dogs euthanized for unrelated medical reasons (controls)., Methods: Prospective, experimental study. Epidural adipose tissue and subcutaneous adipose tissue were collected during dorsal laminectomy and used for real-time quantitative polymerase chain reaction. Tissue explants were cultured for measurements of inflammation-induced release of cytokines., Results: Results show a CES-associated upregulation of the cytokines tumor necrosis factor alpha (TNFα: mean ± SD: 18.88 ± 11.87, 95% CI: 10.90-26.86 vs 9.66 ± 5.22, 95% CI: 5.29-14.02, *: P = .04) and interleukin- (IL-) 10 (20.1 ± 9.15, 95% CI: 14.82-25.39 vs 11.52 ± 6.82, 95% CI: 5.82-17.22, *: P = .03), whereas the expression of the adipokine leptin was attenuated in EAT of dogs with CES (3.07 ± 2.29, 95% CI: 1.80-3.34 vs 9.83 ± 8.42, 95% CI: 3.36-16.30, **: P = .007). Inflammatory stimulation of EAT explant cultures resulted in an enhanced release of IL-6 (LPS: 5491.55 ± 4438, 95% CI: 833.7-10 149; HMGB1: 1001.78 ± 522.2, 95% CI: 518.8-1485; PBS: 310.9 ± 98.57, 95% CI: 228.5-393.3, ***: P < .001)., Conclusion and Clinical Importance: Expression profile of inflammatory adipo(-cyto)kines by EAT is influenced from compressive forces acting in dogs with CES and might contribute to amplification of pain., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Cats are known to be affected by hippocampal sclerosis, potentially causing antiseizure drug(s) resistance. In order to lay the foundation for a standardized, systematic classification and diagnosis of this pathology in cats, this prospective study aimed at evaluating normal reference values of cellular densities and the cytoarchitecture of the feline hippocampus. Three transverse sections (head, body and tail) of each left hippocampus were obtained from 17 non-epileptic cats of different brachycephalic and mesocephalic breeds and age classes (range: 3-17 years). Histological (hematoxylin and eosin, Nissl) and immunohistochemical (NeuN, GFAP) staining was performed to investigate neuron and astroglial cell populations, as well as the layer thickness of the pyramidal cell layer and granule cell layer. Significant differences in neuronal density (in CA2-CA4 and the granule cell layer) and layer thickness (in CA1-CA3 and the granule cell layer) were evidenced throughout the longitudinal hippocampal axis (p<0.05); on the other hand, the astrocyte density did not differ. Moreover, reference ranges were defined for these parameters in the pyramidal cell layer and in the granule cell layer. The findings did not differ according to breed or age. In veterinary medicine these parameters have not been evaluated in cats so far. As surgical treatment may become a therapeutic option for cats with temporal lobe epilepsy, estimating normal values of the hippocampal cytoarchitecture will help in the standardized histopathological examination of resected hippocampal specimens to reach a diagnosis of hippocampal sclerosis., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine cutoff values for the diagnosis of atlantoaxial instability (AAI) based on cross-sectional imaging in small-breed dogs., Study Design: Retrospective multicenter study., Sample Population: Client-owned dogs (n = 123) and 28 cadavers., Methods: Dogs were assigned to three groups: a control group, a "potentially unstable" group, and an AAI-affected group, according to imaging findings and clinical signs. The ventral compression index (VCI), cranial translation ratio (CTR), C1-C2 overlap, C1-C2 angle, atlantoaxial distance, basion-dens interval, dens-to-axis length ratio (DALR), power ratio, and clivus canal angles were measured on CT or T2-weighted magnetic resonance (MR) images. Receiver operating characteristic (ROC) analysis was performed to define cutoff values in flexed (≥25°) and extended (<25°) head positions., Results: Cutoff values for the VCI of ≥0.16 in extended and ≥0.2 in flexed head positions were diagnostic for AAI (sensitivity of 100% and 100%, specificity of 94.54% and 96.67%, respectively). Cutoff values for the other measurements were defined with a lower sensitivity (75%-96%) and specificity (70%-97%). A combination of the measurements did not increase the sensitivity and specificity compared with the VCI as single measurement., Conclusion: Cutoff values for several imaging measurements were established with good sensitivity and specificity. The VCI, defined as the ratio between the ventral and dorsal atlantodental interval, had the highest sensitivity and specificity in both head positions., Clinical Significance: The use of defined cutoff values allows an objective diagnosis of AAI in small-breed dogs. The decision for surgical intervention, however, should remain based on a combination of clinical and imaging findings., (© 2022 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Fully automated synthetic chemistry would substantially change the field by providing broad on-demand access to small molecules. However, the reactions that can be run autonomously are still limited. Automating the stereospecific assembly of Csp 3 -C bonds would expand access to many important types of functional organic molecules 1 . Previously, methyliminodiacetic acid (MIDA) boronates were used to orchestrate the formation of Csp 2 -Csp 2 bonds and were effective building blocks for automating the synthesis of many small molecules 2 , but they are incompatible with stereospecific Csp 3 -Csp 2 and Csp 3 -Csp 3 bond-forming reactions 3-10 . Here we report that hyperconjugative and steric tuning provide a new class of tetramethyl N-methyliminodiacetic acid (TIDA) boronates that are stable to these conditions. Charge density analysis 11-13 revealed that redistribution of electron density increases covalency of the N-B bond and thereby attenuates its hydrolysis. Complementary steric shielding of carbonyl π-faces decreases reactivity towards nucleophilic reagents. The unique features of the iminodiacetic acid cage 2 , which are essential for generalized automated synthesis, are retained by TIDA boronates. This enabled Csp 3 boronate building blocks to be assembled using automated synthesis, including the preparation of natural products through automated stereospecific Csp 3 -Csp 2 and Csp 3 -Csp 3 bond formation. These findings will enable increasingly complex Csp 3 -rich small molecules to be accessed via automated assembly., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Human-directed selective breeding has modified the phenotype of the modern Persian cat towards an extreme brachycephalic phenotype ('peke-face' Persian), which originates from a spontaneous mutation that first appeared in the 1950s in traditional Persian types. It was suggested that the peke-face phenotype results from pathologic skull development and might represent a craniosynostosis of the coronal sutures. We followed this hypothesis and investigated the time dependent status of the neurocranial sutures and synchondroses in an ontogenetic series of doll-faced and peke-faced Persian cats compared to Domestic Shorthair cats (DSHs). Cranial suture closure was assessed by examining an ontogenetic series of formalin-fixed head specimens (n = 55) and dry skulls (n = 32) using micro-computed tomography. Sagittal, metopic, coronal and lambdoid sutures as well as intersphenoidal, spheno-occipital and spheno-ethmoid synchondroses were examined. Logistic regression analysis was performed to test the global effect of age on suture closure within a group of peke-face Persians, doll-face Persians and DSHs and the 50% probability of having a closed suture was calculated and compared between groups. Age was a perfect predictor for the condition of the coronal sutures in peke-face Persians. Coronal sutures were found to be closed at 0-0.3 months. In doll-face and DSHs, coronal sutures were open throughout the lifetime with the exception of a few very old cats. Results of this study confirmed a coronal craniosynostosis that likely causes the extreme brachycephalic skull morphology in the peke-face Persian., (© 2022. The Author(s).)

Objective:  The aim of this study was to describe minimally invasive spinal stabilization using a unilateral uniplanar external skeletal fixator (ESF, type 1a) with polymethylmethacrylate, and to review short- and long-term outcomes and complications in a clinical case series., Study Design:  Medical records from animals affected by spinal fracture luxation were reviewed. The data included breed, age, gender, body weight, aetiology, preoperative and postoperative neurological state, radiographic findings, surgical treatment, pin size, number of pins and stabilized vertebrae, intra- and postoperative complications and neurological state at re-examinations., Results:  Thirty-two animals were identified; three were treated conservatively, 19 surgically and 10 were euthanatized. In eight dogs and six cats, the injured spinal column was treated with a laterally applied percutaneous type 1a ESF under fluoroscopic guidance. Positive profile end-threaded pins inserted were from 1.6/1.9 to 3.5/4.3 mm in dogs and 1.6/1.9 to 2/2.3 mm in cats and were placed into two to five vertebral bodies. At the re-examinations, the neurological status had improved in 12 animals, deteriorated in one, and was unchanged in another one. In eight cases, no complications were detected. The most common complications included erythema, exudation and pin loosening., Conclusion:  The present work shows that type 1a ESF can be successfully and minimally invasively applied to fractures and luxations of the spine in dogs and cats with minimal major complications., Competing Interests: None declared., (Thieme. All rights reserved.)

Placozoans are a promising model system to study fundamental regeneration processes in a morphologically and genetically very simple animal. We here provide a brief introduction to the enigmatic Placozoa and summarize the state of the art of animal handling and experimental manipulation possibilities., (© 2022. The Author(s).)

Neuroinflammation within the superficial dorsal horn (SDH) of the spinal cord induces inflammatory pain with symptoms of hyperalgesia and allodynia. Glial activation and production of inflammatory mediators (e.g. cytokines) is associated with modulation of nociceptive signalling. In this context, medicinal signalling cells, e.g. obtained from adipose tissue (AdMSCs), gained attention due to their capacity to modulate the inflammatory response in several diseases, e.g. spinal cord injury. We applied the recently established mixed neuroglial primary cell culture of the rat SDH to investigate effects of AdMSCs on the inflammatory response of SDH cells. Following establishment of a co-cultivation system, we performed specific bioassays for tumour necrosis factor alpha (TNFα) and interleukin (IL)-6, RT-qPCR and immunocytochemistry to detect changes in cytokine production and glial activation upon inflammatory stimulation with lipopolysaccharide (LPS). LPS-induced expression and release of pro-inflammatory cytokines (TNFα, IL-6) by SDH cells was significantly attenuated in the presence of AdMSCs. Further evidence for anti-inflammatory capacities of AdMSCs derived from a blunted LPS-induced TNFα/IL-10 expression ratio and suppressed nuclear translocation of the inflammatory transcription factor nuclear factor kappa B (NFκB) in SDH microglial cells. Expression of IL-10, transforming growth factor beta (TGF-β) and TNFα-stimulated gene-6 (TSG-6) was detected in AdMSCs, which are putative candidates for anti-inflammatory capacities of these cells. We present a novel co-cultivation system of AdMSCs with neuroglial primary cultures of the SDH to investigate immunomodulatory effects of AdMSCs at a cellular level., (© 2021. The Author(s).)

Lumbosacral vertebral motion is thought to be a factor in the development of degenerative lumbosacral stenosis in German shepherd dogs. So far, few studies exist describing natural canine lumbosacral movement in vivo . Therefore, this investigation aims to achieve a detailed in vivo analysis of bone movement of the lumbosacral region to gain a better understanding of the origin of degenerative lumbosacral stenosis using three-dimensional non-invasive in vivo analysis of canine pelvic and caudal lumbar motion (at L6 and L7). Biplanar cineradiography of the pelvis and caudal lumbar spine of four clinically sound German shepherd dogs at a walk and at a trot on a treadmill was recorded. Pelvic and intervertebral motion was virtually reconstructed and analyzed with scientific rotoscoping. The use of this technique made possible non-invasive measurement of physiological vertebral motion in dogs with high accuracy. Furthermore, the gait patterns of the dogs revealed a wide variation both between individual steps and between dogs. Pelvic motion showed a common basic pattern throughout the stride cycle. Motion at L6 and L7, except for sagittal rotation at a trot, was largely asynchronous with the stride cycle. Intervertebral motion in all dogs was small with approximately 2-3° rotation and translations of approximately 1-2 mm. The predominant motion of the pelvis was axial rotation at a walk, whereas lateral rotation was predominant at a trot. L7 showed a predominance of sagittal rotation (with up to 5.1° at a trot), whereas lateral rotation was the main component of the movement at L6 (about 2.3° in both gaits). During trotting, a coupling of various motions was detected: axial rotation of L7 and the pelvis was inverse and was coupled with craniocaudal translation of L7. In addition, a certain degree of compensation of abnormal pelvic movements during walking and trotting by the caudal lumbar spine was evident., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schaub, Kelleners, Schmidt, Eley and Fischer.)

All vertebrate species have a distinct morphology and movement pattern, which reflect the adaption of the animal to its habitat. Yet, our knowledge of motion patterns of the craniocervical junction of dogs is very limited. The aim of this prospective study is to perform a detailed analysis and description of three-dimensional craniocervical motion during locomotion in clinically sound Chihuahuas and Labrador retrievers. This study presents the first in vivo recorded motions of the craniocervical junction of clinically sound Chihuahuas ( n = 8) and clinically sound Labrador retrievers ( n = 3) using biplanar fluoroscopy. Scientific rotoscoping was used to reconstruct three-dimensional kinematics during locomotion. The same basic motion patterns were found in Chihuahuas and Labrador retrievers during walking. Sagittal, lateral, and axial rotation could be observed in both the atlantoaxial and the atlantooccipital joints during head motion and locomotion. Lateral and axial rotation occurred as a coupled motion pattern. The amplitudes of axial and lateral rotation of the total upper cervical motion and the atlantoaxial joint were higher in Labrador retrievers than in Chihuahuas. The range of motion (ROM) maxima were 20°, 26°, and 24° in the sagittal, lateral, and axial planes, respectively, of the atlantoaxial joint. ROM maxima of 30°, 16°, and 18° in the sagittal, lateral, and axial planes, respectively, were found at the atlantooccipital joint. The average absolute sagittal rotation of the atlas was slightly higher in Chihuahuas (between 9.1 ± 6.8° and 18.7 ± 9.9°) as compared with that of Labrador retrievers (between 5.7 ± 4.6° and 14.5 ± 2.6°), which corresponds to the more acute angle of the atlas in Chihuahuas. Individual differences for example, varying in amplitude or time of occurrence are reported., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schikowski, Eley, Kelleners, Schmidt and Fischer.)

Captive cheetahs often demonstrate a high incidence of diseases in which vitamin A imbalances are implicated. These can occur even under controlled and optimised feeding regimens, which is why surveillance of vitamin A status is mandatory in the successful health management of cheetahs. Serum levels of the vitamin do not reflect the true vitamin A status and liver tissue analysis is rather impractical for routine application in large felids. A biomarker for evaluating overt and subclinical vitamin A deficiency in cheetahs is needed. This study evaluates whether increased calvarial bone thickness can be detected on routine skull radiographs of vitamin A deficient cheetahs compared to unaffected animals, and secondly, evaluates whether there is increased bone thickness in clinically sound captive cheetahs in general compared to wild-living controls. Bone thickness in the neuro- and splanchnocranium was measured in 138 skull radiographs. Significant thickening of the parietal bones was found in latero-lateral radiographs of immature cheetahs (< 12 months) with vitamin A deficiency. This finding may allow a presumptive diagnosis of hypovitaminosis A in immature cheetahs. A general difference in skull thickness between free-living and captive cheetahs was not found., Competing Interests: The authors have declared that no competing interests exist.

For many years, there has been a trend to breed cats with an increasing degree of brachycephalic head features, which are known to have a severe impact on the animals' health and welfare. The direct relation between different grades of brachycephaly and their negative implications have not been researched in this species. The aim of this study was therefore to establish correlations between the different grades of brachycephaly and reduced upper respiratory airways, exophthalmos of the eye globes and malalignment of the teeth in Persian cats. Sixty-nine Persian cats of various skull dimensions and ten Domestic shorthair cats were recruited for the study. The cats' skulls were examined using three-dimensional reconstructions created from Computed Tomography datasets. Brachycephaly was graded using established craniometric measurements (facial index, cranial index, skull index, craniofacial angle). The flow area of the nasal passageways at different locations, the amount of the eye globe not supported by the bony orbit and the axial deviation of the teeth were quantified and evaluated for a correlation with the grade of brachycephaly. The results of this study clearly show that increased grades of brachycephaly in Persian cats resulted in larger extra-orbital parts of the ocular bulbs. The brachycephalic skull dimension also resulted in a lower height of the naso-osseal aperture, while other areas of the nasal airways were not correlated with the severity of brachycephaly. Persian cats showed a significantly increased occurrence of premolar tooth displacement in the upper jaw with increasing brachycephaly grades. It was interesting to note that the measured values had a broad range and values of some individual Persian cats showed an overlap with those of Domestic shorthair cats., Competing Interests: The authors have declared that no competing interests exist.