Xanthinuria in a familial group of Munchkin cats and an unrelated domestic shorthair cat.

CASE SERIES SUMMARY: Four confirmed cases of xanthinuria in cats, and one suspected case based on pedigree analysis, were identified. Clinical presentations varied and included haematuria, pollakiuria, dysuria, and urethral and ureteral obstruction. All cats had upper urinary tract uroliths. Diagnosis was obtained through infrared mass spectrometry of uroliths or urine. Clinical signs commenced at 3-8 months of age and reduced in all cats in the medium to long term after the introduction of a protein-restricted diet. Four cats were castrated males and one was a spayed female. Cases consisted of four Munchkin pedigree cats and one unrelated domestic shorthair cat. All four affected Munchkin pedigree cats were related, with three cases full siblings and the fourth case a half-sibling. No connection to the Munchkin pedigree could be established for the domestic shorthair cat. A candidate causative genetic variant (XDH p.A681V) proposed for this cat was excluded in the Munchkin family. RELEVANCE AND NOVEL INFORMATION: All affected cats presented diagnostic challenges and routine urinalysis was insufficient to obtain a diagnosis. Cases of feline xanthinuria may be underdiagnosed due to situations where uroliths cannot be retrieved for analysis and there is an inability to make a diagnosis using crystal morphology alone on routine urinalysis. Metabolic screening of urine may provide an effective mechanism to confirm xanthinuria in suspected cases where uroliths are inaccessible or absent. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs and urethral obstruction developing secondary to xanthine urolithiasis. A protein-restricted diet appears to reduce clinical signs as part of long-term management. PLAIN LANGUAGE SUMMARY: Four closely related Munchkin cats and one domestic shorthair cat were found with a suspected genetic disease causing high levels of xanthine in their urine. The case series looks at similarities and differences in their clinical signs, as well as difficulties experienced in obtaining a correct diagnosis. All cats had upper urinary tract stones and required metabolic testing of the stones or urine to diagnose. All cats were young when their clinical signs started and were on a high-protein diet. Four cats were desexed males and one was a desexed female. A genetic variant that may have caused the disease in the domestic shorthair cat was ruled out in the Munchkin family. Cases of high xanthine levels in feline urine may be underdiagnosed as the stones may not be accessed for testing. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs. A protein-restricted diet appears to reduce clinical signs as part of long-term management.

An estimation of osteochondrodysplasia prevalence in Australian Scottish Fold cats: a retrospective study using VetCompass Data.

BACKGROUND: All Scottish Fold cats are believed to be affected by osteochondrodysplasia, a painful degenerative joint disorder. This retrospective study aimed to estimate the prevalence of osteochondrodysplasia in Scottish Fold and Scottish Straight cats in Australian veterinary clinics using electronic patient records (EPRs), collected between 1992 and 2018. RESULTS: Consultation events (34,926) in EPRs from veterinary clinics located in New South Wales, Queensland, and Victoria, were collected from 1,131 Scottish Fold and 117 Scottish Shorthair cats. A clinical diagnosis of osteochondrodysplasia was made in 12/1,131 Scottish Fold cats. Additionally, 69 cats were identified with suspected osteochondrodysplasia. Of these, 64 were Scottish Fold and 5 were Scottish Shorthair cats. Male and female cats were equally represented. However, a significant difference was observed for the age clinical signs were first recorded in the EPRs. Cats diagnosed clinically with osteochondrodysplasia were significantly younger (p < 0.0001) compared to cats identified as suspected SFOCD cases. CONCLUSIONS: Findings from this study suggest a relatively low prevalence of clinically diagnosed Scottish Fold osteochondrodysplasia (SFOCD) in the studied Australian Scottish Fold population, with cats generally diagnosed with SFOCD at less than 30 months of age. Further evidence is required to accurately assess the clinical relevance of SFOCD in the Scottish Fold population.

Candidate causative variant for xanthinuria in a Domestic Shorthair cat.

Xanthinuria is a clinically significant form of urolithiasis in cats with poor clinical outcomes and limited treatment options. In humans, xanthinuria has an autosomal recessive mode of inheritance, with variants in xanthine dehydrogenase (XDH) and molybdenum cofactor sulfurase (MOCOS) responsible for cases. While causative genetic variants have not been identified in the domestic cat, a recessive mode of inheritance has been suggested. DNA was extracted from EDTA-stabilised blood obtained from a Domestic Shorthair cat with clinically confirmed xanthinuria. Whole-genome sequencing and variant assessment in XDH and MOCOS identified XDH:c.2042C>T (XDH:p.(A681V)) as a candidate causative variant for xanthinuria in this cat. The variant is located in a highly conserved part of the molybdenum-pterin co-factor domain, responsible for catalysing the hydroxylation of hypoxanthine to xanthine and uric acid. Variants in this domain of XDH have been shown to disrupt enzyme function and to cause xanthinuria in other species. When assessed in the wider cat population, the variant had an allele frequency of 15.8%, with 0.9% of the animals assessed homozygous for the alternative allele. Cats diagnosed with xanthinuria should be tested for this variant to validate its clinical relevance in the wider population.

The Role of Human-Animal Bonds for People Experiencing Crisis Situations.

Human-animal bonds, by providing social support, have been shown to improve the health and wellbeing of pet owners, especially those experiencing a crisis situation. The human-animal bond for people in crisis situations is complex and multifaceted, as it has shown to improve health, whilst it can also discourage people from seeking help, due to fears of leaving their pet behind. The purpose of the study is to capture and to assess the role of the human-animal bond for people in crisis situations. Semi-structured interviews were conducted with pet owners involved in the RSPCA NSW Community Programs (n = 13) in 2021 and 2022. The findings of the study indicate that the human-animal bond is highly valued by people experiencing crisis situations, that the human-animal bonds can affect people's ability to seek help or refuge, and that the human-animal bond helps people to recover after a crisis. The findings suggest that community crisis support services, prison systems, hospital systems, emergency housing, and government legislation should recognize and aim to preserve this bond to provide the best help for people experiencing crisis situations.

Interventions for Promoting Meconium Passage in Very Preterm Infants-A Survey of Current Practice at Tertiary Neonatal Centers in Germany.

Meconium passage is often delayed in preterm infants. Faster meconium passage appears to shorten the time to full enteral feeds, while severely delayed meconium passage may indicate meconium obstruction. Neonatologists often intervene to promote meconium passage, assuming that benefits outweigh potential risks such as necrotizing enterocolitis (NEC). We performed an anonymous online survey on different approaches to facilitate meconium passage among tertiary neonatal intensive care units (NICUs) in Germany between February 2022 and April 2022. We collected information on enteral nutrition, gastrointestinal complications, and interventions to promote meconium passage. We received 102 completed questionnaires (response rate 64.6%). All responders used interventions to promote meconium passage, including enemas (92.0%), orally applied contrast agents (61.8%), polyethylene glycol (PEG) (46.1%), acetylcysteine (19.6%), glycerin suppositories (11.0%), and maltodextrin (8.8%). There was substantial heterogeneity among NICUs regarding frequency, composition, and mode of administration. We found no differences in NEC incidence between users and nonusers of glycerin enemas, high or low osmolar contrast agents, or PEG. There is wide variability in interventions used to promote meconium passage in German NICUs, with little or no evidence for their efficacy and safety. Within this study design, we could not identify an increased risk of NEC with any intervention reported.

Feline Skeletal Reference Guide: A Cadaveric Radiographic Measurement on Lower Limb Extremities.

OBJECTIVE: The aim of this study was to create a feline reference database for the length, width and slenderness (length to width ratio) of metacarpal and metatarsal bones, radius and tibia. STUDY DESIGN: Radiographs of the radius, tibia, metacarpus and metatarsus were performed in domestic short hair cat cadavers (n = 40). Length and width of the aforementioned bones were measured in mature domestic shorthair cats and bone slenderness (length/width) and index ratios calculated. RESULTS: A significant skeletal sex dimorphism exists in cats, with bones of the metacarpus, metatarsus, radius and tibia generally longer and wider in male cats compared with female cats, with differences frequently significant. The most significant difference was identified for the width of Mc5 (p = 0.0008) and the length and width of Mt5 (p = 0.0005). Index ratios for length and width of radius to metacarpal bones, and tibia to metatarsal bones, were not significantly different between male and female cats, except for Mc5. The index ratio for Mc5 was significantly higher in male cats (p = 0.002). CONCLUSION: The present study provides insights into the normal length and width of distal forelimb and hind limb bones as well as bone index ratios in mature domestic shorthair cats. Using this information, it is now possible to quantitatively assess the relationship between these bones in domestic cats using radiography. This will assist not only with the diagnosis and categorization of skeletal abnormalities but can also guide surgical interventions of metacarpal and metatarsal bone fractures.

Comparison of nostril sizes of newborn infants with outer diameter of endotracheal tubes.

BACKGROUND: Recommendations for endotracheal tube (ETT) size usually refer to the inner diameter (ID). Outer diameters (OD), however, vary greatly between manufacturers, which in some brands might cause difficulties in passing the ETT through the nostrils if choosing the nasal route for intubation. Even though the nostrils are dilatable by an ETT, it might be difficult to pass an ETT through the posterior naris (narrowest point of the nasal passage), if the OD is bigger than the nostrils. Therefore, nostril size may provide some guidance for the appropriate ETT size preventing unsuccessful intubation attempts. This study therefore compares nostril sizes of newborn infants with ODs of ETTs from several manufacturers. METHODS: This is a subgroup analysis of a prospective observational study, performed in a single tertiary perinatal centre in Germany. The diameter of the nostril of infants born between 34 and 41 weeks´ gestation was measured in 3D images using 3dMDvultus software and compared to the OD of ETT from five different manufacturers. RESULTS: Comparisons of nostril sizes with ODs of different ETTs were made for 99 infants with a mean (SD) birthweight of 3058g (559) [range: 1850-4100g]. Mean (SD) nostril size was 5.3mm (0.6). The OD of the 3.5mm ETT of different manufacturers ranged from 4.8-5.3mm and was thus larger than the nostril size of 20-46% of late preterm or term infants. Some OD of a 3.0mm ETT were even bigger than the OD of a 3.5mm ETT (e.g. the 3.0mm ETT from Rüsch® has an OD of 5.0mm while the 3.5mm ETT from Portex® has an OD of 4.8mm). CONCLUSIONS: Clinicians should be aware of the OD of ETTs to reduce unsuccessful intubation attempts caused by ETT sizes not fitting the nasal cavity. Generated data may help to adapt recommendations in future. TRIAL REGISTRATION: Subgroup analysis of the "Fitting of Commonly Available Face Masks for Late Preterm and Term Infants (CAFF)"-study: NCT03369028, www.ClinicalTrials.gov , December 11, 2017.

Exploiting genomic synteny in Felidae: cross-species genome alignments and SNV discovery can aid conservation management.

BACKGROUND: While recent advances in genomics has enabled vast improvements in the quantification of genome-wide diversity and the identification of adaptive and deleterious alleles in model species, wildlife and non-model species have largely not reaped the same benefits. This has been attributed to the resources and infrastructure required to develop essential genomic datasets such as reference genomes. In the absence of a high-quality reference genome, cross-species alignments can provide reliable, cost-effective methods for single nucleotide variant (SNV) discovery. Here, we demonstrated the utility of cross-species genome alignment methods in gaining insights into population structure and functional genomic features in cheetah (Acinonyx jubatas), snow leopard (Panthera uncia) and Sumatran tiger (Panthera tigris sumatrae), relative to the domestic cat (Felis catus). RESULTS: Alignment of big cats to the domestic cat reference assembly yielded nearly complete sequence coverage of the reference genome. From this, 38,839,061 variants in cheetah, 15,504,143 in snow leopard and 13,414,953 in Sumatran tiger were discovered and annotated. This method was able to delineate population structure but limited in its ability to adequately detect rare variants. Enrichment analysis of fixed and species-specific SNVs revealed insights into adaptive traits, evolutionary history and the pathogenesis of heritable diseases. CONCLUSIONS: The high degree of synteny among felid genomes enabled the successful application of the domestic cat reference in high-quality SNV detection. The datasets presented here provide a useful resource for future studies into population dynamics, evolutionary history and genetic and disease management of big cats. This cross-species method of variant discovery provides genomic context for identifying annotated gene regions essential to understanding adaptive and deleterious variants that can improve conservation outcomes.

An approach to define newborns´ sniffing position using an angle based on reproducible facial landmarks.

BACKGROUND: The neutral or sniffing position is advised for mask ventilation in neonates to avoid airway obstruction. As definitions are manifold and often unspecific, we wanted to investigate the reliability and reproducibility of angle measurements based on facial landmarks that may be used in future clinical trials to determine a hypothetical head position with minimal airway obstruction during mask ventilation. METHODS: In a prospective single-center observational study, 2D sagittal photographs of 24 near-term and term infants were taken, with five raters marking facial landmarks to assess interobserver agreement of those landmarks and angle δ, defined as the angle between the line parallel to the lying surface and the line crossing Subnasale (Sn) and Porion' (P'). Angle δ was assessed in sniffing (δsniff ) and physiologic (δphys ) head position, the former based on a published, yet poorly defined head position where the tip of the nose aligns to the ceiling with the head in a supine, relaxed mid-position. RESULTS: Infants had a mean (SD) gestational age of 37.3 (2.3) weeks. Angle δ could be determined in all 48 images taken in either the sniffing or the physiological head position. Interobserver correlation coefficient was 98.6 for all measurements independent of head position. Angle δsniff was 90.5° (5.7) in the sniffing position. CONCLUSIONS: This study provides a new measuring technique using an angle that is reproducible and reliable and may be used in future studies to correlate head position with airway obstruction.

Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus).

Diabetes mellitus, a common endocrinopathy affecting domestic cats, shares many clinical and pathologic features with type 2 diabetes in humans. In Australia and Europe, diabetes mellitus is almost four times more common among Burmese cats than in other breeds. As a genetically isolated population, the diabetic Australian Burmese cat provides a spontaneous genetic model for studying diabetes mellitus in humans. Studying complex diseases in pedigreed breeds facilitates tighter control of confounding factors including population stratification, allelic frequencies and environmental heterogeneity. We used the feline SNV array and whole genome sequence data to undertake a genome wide-association study and runs of homozygosity analysis, of a case-control cohort of Australian and European Burmese cats. Our results identified diabetes-associated haplotypes across chromosomes A3, B1 and E1 and selective sweeps across the Burmese breed on chromosomes B1, B3, D1 and D4. The locus on chromosome B1, common to both analyses, revealed coding and splice region variants in candidate genes, ANK1, EPHX2 and LOX2, implicated in diabetes mellitus and lipid dysregulation. Mapping this condition in Burmese cats has revealed a polygenic spectrum, implicating loci linked to pancreatic beta cell dysfunction, lipid dysregulation and insulin resistance in the pathogenesis of diabetes mellitus in the Burmese cat.

Randomized Longitudinal Study Comparing Three Nasal Respiratory Support Modes to Prevent Intermittent Hypoxia in Very Preterm Infants.

Nasal continuous positive airway pressure (NCPAP) devices using variable (vf-) and continuous (cf-) flow or synchronized nasal intermittent positive pressure ventilation (s-NIPPV) are used to prevent or treat intermittent hypoxia (IH) in preterm infants. Results concerning which is most effective vary. We aimed to investigate the effect of s-NIPPV and vf-NCPAP compared to cf-NCPAP on the rate of IH episodes. Preterm infants with a gestational age of 24.9-29.7 weeks presenting with IH while being treated with cf-NCPAP were monitored for eight hours, then randomized to eight hours of treatment with vf-NCPAP or s-NIPPV. Data from 16 infants were analyzed. Due to an unexpectedly low sample size, the results were only reported descriptively. No relevant changes in the rate of IH events were detected between cf- vs. vf-NCPAP or between cf-NCPAP vs. s-NIPPV. Although limited by its small sample size, s-NIPPV, vf- and cf-NCPAP seemed to be similarly effective in the treatment of IH in these infants.

Evaluating practioners' preferences regarding vascular emergency access in newborn infants in the delivery room: a national survey.

BACKGROUND: Venous access during neonatal emergencies in the delivery room (DR) can be accomplished through an umbilical venous catheter (UVC) or an intraosseous (IO) access. Preference of one over the other is unclear. We wanted to evaluate practioners' views. METHODS: An anonymous online questionnaire was circulated to healthcare professionals with different background and experience, all working in neonatal intensive care units in Germany. The web-based survey consisted of 13 questions and data collection was performed using an online tool. RESULTS: We received 502 completed questionnaires, 152 (30%) were from neonatologists, the remainder from residents, fellows and neonatal nurses. For resuscitation of term newborns in the DR 61% of neonatologists vs. 53% of non-neonatologists were in favour of UVC instead of an IO as an emergency access. UVC placement was rated (very) difficult to impossible by 60% of neonatologists and 90% of non-neonatologists (p < 0.05). All respondents cited lack of experience as the main reason for feeling reluctant to place an UVC or IO access, the latter only being taken into consideration in term infants. CONCLUSIONS: UVC placement in the DR is rated more often difficult to use by non-neonatologists than by neonatologists, apparently related to lack of experience. IO access was only considered for resuscitating term infants due to lacking practice and missing approval for birth weights < 3000 g. Frequent training might improve these clinical skills.

Do commonly available round facemasks fit near-term and term infants?

OBJECTIVE: With inappropriately large facemasks, it is more difficult to create a seal on the face, potentially leading to ineffective ventilation during neonatal stabilisation. We investigated whether commonly available round facemasks are of appropriate size by measuring facial dimensions in near-term and term infants using two-dimensional (2D) and three-dimensional (3D) images. DESIGN: Prospective single-centre observational study. SETTING: Infants born in our centre at 34-41 weeks' gestation were eligible. INTERVENTION: Patients were photographed with 2D and 3D technique. MAIN OUTCOME MEASURES: Distances between nasion and gnathion were measured and compared with the outer diameter of various round facemasks. METHODS: 2D and 3D images were performed using standard equipment. Correlations between gestational age and the above-mentioned distances were assessed using Pearson's r. RESULTS: Images were taken from 102 infants with a mean (SD) gestational age of 37.9 (2.3) weeks. Mean distance between nasion and gnathion was 46.9 mm (5.1) in 2D and 49.9 mm (4.1) in 3D images, that is, on average 3 mm smaller in 2D than with 3D (p<0.01). Based on these measurements, round facemasks with an external diameter of 50 mm seemed fitting for most (61%) term infants and 42 mm masks for most (72%) near-term infants (GA 34-36 weeks). CONCLUSIONS: Round facemasks with an external diameter of 60 mm are too large for almost all newborn infants, while 42/50 mm round facemasks are well fitting. Important anatomical structures were only visible using 3D images. CLINICAL TRIAL REGISTRATION NUMBER: NCT03369028.

Correction: Mutations in MITF and PAX3 Cause "Splashed White" and Other White Spotting Phenotypes in Horses.

[This corrects the article DOI: 10.1371/journal.pgen.1002653.].

Genomic Characterization of External Morphology Traits in Kelpies Does Not Support Common Ancestry with the Australian Dingo.

The Kelpie is a breed developed in Australia for use as a livestock herding dog. It has been proposed that the development of the breed included gene flow from the Australian Dingo (Canis dingo), a canid species present on the Australian continent for around 4000 years. The Kelpie breed is split between working and conformation types that have readily recognizable differences in external morphology. We characterize known gene variants relating to external morphology in sequenced representatives of both Kelpie types (Australian Kelpie-conformation; Australian Working Kelpie-herding) and compare the variants present with those in sequenced Australian Dingoes, including 25 canids with locus-constrained data and one with a whole genome sequence. Variants assessed include identified coat color and ear morphology variants. We describe a new variant site in the transcribed region of methionine sulfoxide reductase 3 that may relate to ear phenotype. None of the morphology variants analyzed offer support for co-ancestry of the Kelpie breed with the Australian Dingo.