The larynx is an essential organ in mammals with three primary functions - breathing, swallowing, and vocalizing. A wide range of disorders are known to impair laryngeal function, which results in difficultybreathing (dyspnea), swallowing impairment (dysphagia), and/or voice impairment (dysphonia). Dysphagia, in particular, can lead to aspiration pneumonia and associated morbidity, recurrent hospitalization, and early mortality. Despite these serious consequences, existing treatments for laryngeal dysfunction are largely aimed at surgical and behavioral interventions that unfortunately do not typically restore normal laryngeal function, thus highlighting the urgent need for innovative solutions. To bridge this gap, we have been developing an experimental endoscopic approach to investigate laryngeal dysfunction in murine (i.e., mouse and rat) models. However, endoscopy in rodents is quite challenging due to their small size relative to current endoscope technology, anatomical differences in the upper airway, and the necessity for anesthesia to optimally access the larynx. Here, we describe a novel transoral laryngoscopy approach that permits close-up, unobstructed video imaging of laryngeal motion in mice and rats. Critical steps in the protocol include precise anesthesia management (to prevent overdosing that abolishes swallowing and/or risks respiratory distress-related mortality) and micromanipulator control of the endoscope (for stable video recording of laryngeal motion by a single researcher for subsequent quantification). Importantly, the protocol can be performed over time in the same animals to study the impact of various pathological conditions specifically on laryngeal function. A novel advantage of this protocol is the ability to visualize airway protection during swallowing, which is not possible in humans due to epiglottic inversion over the laryngeal inlet that obstructs the glottis from view. Rodents therefore provide a unique opportunity to specifically investigate the mechanisms of normal versus pathological laryngeal airway protection for the ultimate purpose of discovering treatments to effectively restore normal laryngeal function.

Whole blood viscosity, a hemorheological factor, is currently used for diagnosis, as it is correlated with various vascular diseases that are difficult to diagnose early with a general blood test. It was determined that it was necessary to set reference intervals for further studies and utilization of whole blood viscosity in cats, a representative companion animal, and this study was conducted. Fifty healthy cats were recruited for the study, and whole blood viscosity, complete blood count, and serum chemistry tests were performed. The reference intervals of whole blood viscosity were 15.169 to 43.684 cP at a shear rate of 1 s−1 reflecting diastole, and 3.524 to 5.544 cP at a shear rate of 300 s−1 reflecting systole. Red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils in the complete blood count, and total protein, albumin, globulin, and cholesterol in the serum chemistry were significantly correlated with whole blood viscosity. The results of this study set the reference intervals of whole blood viscosity for healthy cats in a wide shear rate range that has not yet been fully established, and its correlation with other blood indicators investigated.

Domestic cats were derived from the Near Eastern wildcat (Felis lybica), after which they dispersed with people into Europe. As they did so, it is possible that they interbred with the indigenous population of European wildcats (Felis silvestris). Gene flow between incoming domestic animals and closely related indigenous wild species has been previously demonstrated in other taxa, including pigs, sheep, goats, bees, chickens, and cattle. In the case of cats, a lack of nuclear, genome-wide data, particularly from Near Eastern wildcats, has made it difficult to either detect or quantify this possibility. To address these issues, we generated 75 ancient mitochondrial genomes, 14 ancient nuclear genomes, and 31 modern nuclear genomes from European and Near Eastern wildcats. Our results demonstrate that despite cohabitating for at least 2,000 years on the European mainland and in Britain, most modern domestic cats possessed less than 10% of their ancestry from European wildcats, and ancient European wildcats possessed little to no ancestry from domestic cats. The antiquity and strength of this reproductive isolation between introduced domestic cats and local wildcats was likely the result of behavioral and ecological differences. Intriguingly, this long-lasting reproductive isolation is currently being eroded in parts of the species' distribution as a result of anthropogenic activities.

The European wildcat population in Scotland is considered critically endangered as a result of hybridization with introduced domestic cats,1,2 though the time frame over which this gene flow has taken place is unknown. Here, using genome data from modern, museum, and ancient samples, we reconstructed the trajectory and dated the decline of the local wildcat population from viable to severely hybridized. We demonstrate that although domestic cats have been present in Britain for over 2,000 years,3 the onset of hybridization was only within the last 70 years. Our analyses reveal that the domestic ancestry present in modern wildcats is markedly over-represented in many parts of the genome, including the major histocompatibility complex (MHC). We hypothesize that introgression provides wildcats with protection against diseases harbored and introduced by domestic cats, and that this selection contributes to maladaptive genetic swamping through linkage drag. Using the case of the Scottish wildcat, we demonstrate the importance of local ancestry estimates to both understand the impacts of hybridization in wild populations and support conservation efforts to mitigate the consequences of anthropogenic and environmental change.

Salmonella is a foodborne zoonotic bacterium, and the antimicrobial-resistant strains of Salmonella are a worldwide health concern. Herein, we employed a meta-analysis to determine the pooled prevalence of Salmonella and its antimicrobial resistance status in human, animal, and environmental isolates in South Asia. To this end, we followed the standard guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements for searching literature in three databases namely PubMed, Google Scholar, and CAB abstracts, and a total of 100 eligible datasets were finally included which were published from January 2010 to June 2021. In the pooled prevalence of Salmonella in South Asia, the random model effect was 14.47% (95% CI: 10.17–20.19) with a high degree of heterogeneity (I2, 99.8%) and overall antimicrobial resistance was 70% (95% CI: 63.0–76.0) with a heterogeneity of 23.6%. The temporal distribution of the overall antimicrobial resistance (%) against Salmonella was increased from 53 to 77% within 10 years. Out of 18 distinct Salmonella serotypes, S. enterica was highly prevalent (14.22%, 95% CI: 4.02–39.64) followed by S.pullorum (13.50%, 95% CI: 5.64–29.93) with antimicrobial resistance (%) were 86.26 and 90.06, respectively. Noteworthy, nalidixic acid (74.25%) and tetracycline (37.64%) were found mostly resistant to Salmonella whereas ceftriaxone (1.07%) and cefixime (1.24%) were sensitive. This systematic review demonstrated that overall antibiotic resistance profiles of Salmonella are increasing over time in South Asia. Thus, adequate hygienic practices, proper use of antimicrobials, and implementation of antibiotic stewardship are imperative for halting the Salmonella spread and its antimicrobial resistance.

IntroductionDiet-associated dilated cardiomyopathy (DCM) has been suspected in breeds that have not been previously noted to have a predisposition to the DCM phenotype. This study hypothesized that over 210 days, dogs fed diets with varying amounts of animal-sourced protein and carbohydrate sources would not be negatively impacted in terms of their cardiac parameters and function.MethodsThirty-two purebred beagles and 33 mixed-breed hounds were randomized into four diet groups and studied for 210 days. The diet groups were as follows: the high-animal-protein grain-free (HAGF) group, the low-animal-protein grain-free (LAGF) group, the high-animal-protein grain-inclusive (HAGI), and the low-animal-protein grain-inclusive (LAGI) group. Cardiac-specific biomarkers, endomyocardial biopsies, and linear and volumetric echocardiographic parameters were evaluated.ResultsThere was a treatment-by-day-by-breed effect observed for the normalized left ventricular internal diameter at end-diastole (p = 0.0387) and for the normalized left ventricular internal diameter at end-systole (p = 0.0178). On day 210, mixed-breed hounds fed the LAGI diet had a smaller normalized left ventricular internal diameter at end-diastole than on day 90. On day 210, beagles fed the LAGF diet had a larger normalized left ventricular internal diameter at end-systole than those fed the LAGI diet. Fractional shortening for beagles in the LAGF group was significantly lower (p = 0.007) than for those in the HAGI and LAGI groups. Cardiac-specific biomarkers and endomyocardial biopsies were not significantly different between breeds, diets, and various time points.DiscussionThis study did not detect the development of cardiac dysfunction throughout the study period through the echocardiographic parameters measured, select cardiac biomarkers, or endomyocardial biopsies. There were noted interactions of treatment, breed, and time; therefore, isolating a diet association was not possible. Future research should further investigate the other factors that may help to identify the variable(s) and possible mechanisms underlying suspected diet-associated DCM in dogs.

In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal. The model-predicted outputs are found to be consistent with published clinical data. Model simulations suggest that the balance between the contractile function of the left ventricle and the load opposed by the arterial circulation attains similar levels in females and males, but is achieved through different combinations of factors. Additionally, we examine the potential of using the BCG waveform, which is directly related to cardiovascular volumes, as a noninvasive method for monitoring cardiovascular function. Our findings provide valuable insights into the underlying mechanisms of cardiovascular sex differences and may help facilitate the development of effective noninvasive cardiovascular monitoring methods for early diagnosis and prevention of cardiovascular disease in both women and men.

The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats. Clinical and genetic analyses were conducted on a Siamese cat family (n = 18), including two siblings with RH. Radiographs were obtained for the affected kittens and echocardiograms of an affected kitten and sire. Whole genome sequencing was completed on the two cases and the parents. Genomic data were compared with the 99 Lives Cat Genome data set of 420 additional domestic cats with whole genome and whole exome sequencing data. Variants were considered as homozygous in the two cases of the siblings with RH and heterozygous in the parents. Candidate variants were genotyped by Sanger sequencing in the extended pedigree. Radiographs of the female kitten revealed bilateral absence of the radii and bowing of the humeri, while the male kitten showed a dysplastic right radius. Echocardiography suggested the female kitten had restrictive cardiomyopathy with a positive left atrial-to-aortic root ratio (LA:Ao = 1.83 cm), whereas hypertrophic cardiomyopathy was more likely in the sire, showing diastolic dysfunction using tissue Doppler imaging (59.06 cm/s). Twenty-two DNA variants were unique and homozygous in the affected kittens and heterozygous in the parents. Seven variants clustered in one chromosomal region, including two frameshift variants in cardiomyopathy associated 5 (CMYA5) and five variants in junction mediating and regulatory protein, P53 cofactor (JMY ), including a missense and an in-frame deletion. The present study suggested an autosomal recessive mode of inheritance with variable expression for RH in the Siamese cat family. Candidate variants for the phenotype were identified, implicating their roles in bone development. These genes should be considered as potentially causal for other cats with RH. Siamese cat breeders should consider genetically testing their cats for these variants to prevent further dissemination of the suspected variants within the breed.

To describe a novel scoring system of feline pigmented iris lesions prior to utilization of diode laser ablation of progressive pigmented iris lesions and to retrospectively evaluate short- and long-term patient outcomes following transcorneal diode laser ablation. 317 client-owned cats (356 eyes) were included. Records of cats undergoing diode laser ablation from January 2000 to December 2018 were retrospectively reviewed. A novel clinical grading system to describe severity of feline iris hyperpigmentation was developed. Recorded parameters included signalment, operated-upon eye, presurgical iris pigmentation score, intraocular pressure, visual status, postoperative complications, repeat laser surgery, patient status at last follow-up, time to death, and presumptive or known cause of death. Complications included corneal ulceration (25/356 [7%]), glaucoma (18/356 [5%]), uveitis (4/356 [1.1%]), and corneal edema (3/356 [0.8%]). Enucleation was performed in 12 eyes due to blindness and secondary glaucoma. Repeat laser due to continued progression of pigment was performed in 18.5% of eyes. Two study patients were euthanized due to presumptive metastatic disease. Of the 250 cats for whom confirmation was available via phone call or medical records, 240 (96%) were alive at 1 year. Diode laser ablation appears safe overall and may be effective in decreasing progression of feline iris pigmentation. Complication risks appear minimal.

Anecdotally, adults reach higher levels of subjective intoxication on days they are fatigued or sleep-deprived, but sleep is not typically discussed as a predictor of blood alcohol concentration (BAC) in clinical settings. To inform clinical work and future research, this perspective reviews data examining the impact of sleep (process S) and circadian (process C) factors on indicators of BAC in humans and animal models. Literature searches of medical and psychological databases were conducted to identify articles that manipulated sleep/circadian factors and reported effects on indicators of alcohol pharmacology (e.g. BAC, alcohol metabolism). Of the 86 full-text articles reviewed, 21 met inclusion criteria. Studies included manipulations of time of day, circadian phase (evidence for process C), and time in bed (evidence for process S). Evidence for time-of-day effects on alcohol pharmacology was most compelling. Studies also provided evidence for circadian phase effects, but failed to find support for time-in-bed effects. Although results were not uniform across studies, most evidence from human and animal models indicates that peak BACs occur toward the beginning of the biological day, with some studies indicating slower alcohol elimination rates at this time. Circadian factors likely influence alcohol pharmacokinetics, perhaps due to altered elimination of alcohol from the body. This means that individuals may reach higher BACs if they drink during the morning (when, for most people, circadian alerting is low) versus other times of the day. Alcohol prevention and intervention efforts should highlight sleep/circadian health as a potential contributor to alcohol-related harm.