Cat Model Research Articles

Extracellular vesicles are involved in the paracrine communication between epithelial cells in different regions of the domestic cat epididymis.

Sperm maturation depends on exposure to specific microenvironments within the different segments of the epididymis, but mechanisms underlying how these microenvironments are produced or maintained are not well understood. We hypothesized that epididymal extracellular vesicles (EVs) could play a role in the process of maintaining microenvironments in different regions of the epididymis. Specifically, we tested whether the EVs from different regions of the epididymis can serve as a form of paracrine communication between cells in different segments. Domestic cat tissues were used to develop a reproducible in vitro culture system for corpus epididymis explants that were then exposed to EVs collected from upstream (i.e. caput) segments. The impacts of different culture or exposure conditions were compared by analyzing the morphology, apoptosis, transcriptional activity, and gene expression in the explants. Here, we report the development of the first in vitro culture system for epididymal tissue explants in the domestic cat model. Using this system, we found that EVs from the caput segment have a significant effect on the transcriptional profile of tissue from the corpus segment (1233 differentially expressed genes due to EV supplementation). Of note, expression of genes associated with regulation of epithelial cell differentiation and cytokine signaling in the epididymis were regulated by the presence of EVs. Together, our findings comprise the first report of paracrine control of segmental gene regulation by epididymal EVs in any species. These results contribute to a better understanding of epididymis biology and could lead to techniques to enhance or suppress male fertility.

Exploring the potential of machine learning to understand the occurrence and health risks of haloacetic acids in a drinking water distribution system

Determining the occurrence of disinfection byproducts (DBPs) in drinking water distribution system (DWDS) remains challenging. Predicting DBPs using readily available water quality parameters can help to understand DBPs associated risks and capture the complex interrelationships between water quality and DBP occurrence. In this study, we collected drinking water samples from a distribution network throughout a year and measured the related water quality parameters (WQPs) and haloacetic acids (HAAs). 12 machine learning (ML) algorithms were evaluated. Random Forest (RF) achieved the best performance (i.e., R2 of 0.78 and RMSE of 7.74) for predicting HAAs concentration. Instead of using cytotoxicity or genotoxicity separately as the surrogate for evaluating toxicity associated with HAAs, we created a health risk index (HRI) that was calculated as the sum of cytotoxicity and genotoxicity of HAAs following the widely used Tic-Tox approach. Similarly, ML models were developed to predict the HRI, and RF model was found to perform the best, obtaining R2 of 0.69 and RMSE of 0.38. To further explore advanced ML approaches, we developed 3 models using uncertainty-based active learning. Our findings revealed that Categorical Boosting Regression (CAT) model developed through active learning substantially outperformed other models, achieving R2 of 0.87 and 0.82 for predicting concentration and the HRI, respectively. Feature importance analysis with the CAT model revealed that temperature, ions (e.g., chloride and nitrate), and DOC concentration in the distribution network had a significant impact on the occurrence of HAAs. Meanwhile, chloride ion, pH, ORP, and free chlorine were found as the most important features for HRI prediction. This study demonstrates that ML has the potential in the prediction of HAA occurrence and toxicity. By identifying key WQPs impacting HAA occurrence and toxicity, this research offers valuable insights for targeted DBP mitigation strategies.

Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: "A Spoonful of Sugar Helps the Medicine Go Down".

Viral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA)in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation. This enables titratable gene delivery with unprecedently low charge transfer. The clinic-ready bionics-derived CC-GET device achieved neurotrophin-encoding miniplasmid DNA delivery to the cochlea to promote auditory nerve regeneration; validated in deafened guinea pig and cat models, leading to improved central auditory tuning with bionics-based hearing. The performance of CC-GET is evaluated in the brain, an organ problematic for pulsed electric field-based plasmid DNA delivery, due to high required currents causing Joule-heating and damaging electroporation. Here CC-GET enables safe precision targeting of gene expression. In the guinea pig, reporter expression is enabled in physiologically critical brainstem regions, and in the striatum (globus pallidus region) delivery of a red-shifted channelrhodopsin and a genetically-encoded Ca2+sensor, achieved photoactivated neuromodulation relevant to the treatment of Parkinson's Disease and other focal brain disorders.

Exploring the Consistent Roles of Motor Areas Across Voluntary Movement and Locomotion.

Multiple cortical motor areas are critically involved in the voluntary control of discrete movement (e.g., reaching) and gait. Here, we outline experimental findings in nonhuman primates with clinical reports and research in humans that explain characteristic movement control mechanisms in the primary, supplementary, and presupplementary motor areas, as well as in the dorsal premotor area. We then focus on single-neuron activity recorded while monkeys performed motor sequences consisting of multiple discrete movements, and we consider how area-specific control mechanisms may contribute to the performance of complex movements. Following this, we explore the motor areas in cats that we have considered as analogs of those in primates based on similarities in their cortical surface topology, anatomic connections, microstimulation effects, and activity patterns. Emphasizing that discrete movement and gait modification entail similar control mechanisms, we argue that single-neuron activity in each area of the cat during gait modification is compatible with the function ascribed to the activity in the corresponding area in primates, recorded during the performance of discrete movements. The findings that demonstrate the premotor areas' contribution to locomotion, currently unique to the cat model, should offer highly valuable insights into the control mechanisms of locomotion in primates, including humans.

A NEW POSTURAL MOTOR RESPONSE TO SPINAL CORD STIMULATION: POST-STIMULATION REBOUND EXTENSION.

Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.

Is the mouse nose a miniature version of a rat nose? A computational comparative study

Background and objectiveAlthough the mouse is a widely used animal model in biomedical research, there are few published studies on its nasal aerodynamics, potentially due to its small size. It is not appropriate to assume that mice and rats' nasal structure and airflow characteristics are the same because the ratio of nasal surface area to nasal volume and body weight is much higher in a mouse than in a rat. The aim of this work is to use anatomically accurate image-based computational fluid dynamic modeling to quantitatively reveal the characteristics of mouse nasal airflow and mass transport that haven't been detailed before and find key differences to that of rat nose, which will deepen our understanding of the mouse's physiological functions. MethodsWe created an anatomically accurate 3D computational nasal model of a B6 mouse using postmortem high-resolution micro-CT scans and simulated the airflow distribution and odor transport patterns under restful breathing conditions. The deposition pattern of airborne particles was also simulated and validated against experimental data. In addition, we calculated the gas chromatograph efficiency of odor transport in the mouse employing the theoretical plate concept and compared it with previous studies involving cat and rat models. ResultsSimilar to the published rat model, respiratory and olfactory flow regimes are clearly separated in the mouse nasal cavity. A high-speed dorsal medial (DM) stream was observed, which enhances the delivery speed and efficiency of odor to the ethmoid (olfactory) recess (ER). The DM stream split into axial and secondary paths in the ER. However, the secondary flow in the mouse is less extensive than in the rat. The gas chromatograph efficiency calculations suggest that the rat may possess a moderately higher odorant transport efficiency than that of the mouse due to its more complex ethmoid recess structure and extensive secondary flow. However, the mouse's nasal structure seems to adapt better to varying airflow velocity. ConclusionsDue to the inherent structural disparities, the rat and mouse models exhibit moderate differences in airflow and mass transport patterns, potentially impacting their olfaction and other behavioral habits.

Toward telomere-to-telomere cat genomes for precision medicine and conservation biology.

Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat models has revealed dozens of health-related genetic variants, the molecular basis for mammalian pigmentation and patterning, and species-specific adaptations. Improved genomic surveillance of natural and captive populations across the cat family tree will increase our understanding of the genetic architecture of traits, population dynamics, and guide a future of genome-enabled biodiversity conservation.

Functional mapping of the lower urinary tract by epidural electrical stimulation of the spinal cord in decerebrated cat model

Several neurologic diseases including spinal cord injury, Parkinson’s disease or multiple sclerosis are accompanied by disturbances of the lower urinary tract functions. Clinical data indicates that chronic spinal cord stimulation can improve not only motor function but also ability to store urine and control micturition. Decoding the spinal mechanisms that regulate the functioning of detrusor (Detr) and external urethral sphincter (EUS) muscles is essential for effective neuromodulation therapy in patients with disturbances of micturition. In the present work we performed a mapping of Detr and EUS activity by applying epidural electrical stimulation (EES) at different levels of the spinal cord in decerebrated cat model. The study was performed in 5 adult male cats, evoked potentials were generated by EES aiming to recruit various spinal pathways responsible for LUT and hindlimbs control. Recruitment of Detr occurred mainly with stimulation of the lower thoracic and upper lumbar spinal cord (T13-L1 spinal segments). Responses in the EUS, in general, occurred with stimulation of all the studied sites of the spinal cord, however, a pronounced specificity was noted for the lower lumbar/upper sacral sections (L7-S1 spinal segments). These features were confirmed by comparing the normalized values of the slope angles used to approximate the recruitment curve data by the linear regression method. Thus, these findings are in accordance with our previous data obtained in rats and could be used for development of novel site-specific neuromodulation therapeutic approaches.

Cat presumptive zygotes assessment in relation to their development

Abstract The evaluation of oocytes and zygotes, based on their size, shape and morphology, is a valuable tool for predicting subsequent embryo development. While this assessment is non-invasive and made possible with time-lapse monitoring systems, not all the assessment criteria used for zygotes with pale cytoplasm can be used for domestic cat zygotes, which have dark cytoplasm. In this study, feline presumptive zygotes were evaluated for shape, size, and morphology. Measurements were also made of the diameter of the entire zygote, its cytoplasm, and the zona pellucida. Differences in the dataset were assessed using the generalized linear model (GLM) procedure. While there was no relationship between a combination of the tested parameters with the potential for cleavage, blastocyst development, and hatching, the parameters of the shape and size of the entire oocyte, and of the zona pellucida, were related to the development potential. The results presented in this study indicate that the assessment procedure for human zygotes has to be adjusted to be used in the cat model, however the relationship between measurements of the diameter of presumptive feline zygotes and the thickness of zona pellucida with their developmental potential deserves further investigation to optimize assessment of cat presumptive zygotes.

Predicting compressive and flexural strength of high-performance concrete using a dynamic Catboost Regression model combined with individual and ensemble optimization techniques

Compressive Strength (CS) and Flexural Strength (FS) cannot be overstated when designing reinforced concrete structures, as industry standards govern these factors. Creating reliable predictive models for these properties offers the potential to enhance cost-effectiveness and efficiency by decreasing the necessity for numerous rounds of lab testing and iterative experiments, which are essential for obtaining valuable design information. In construction, evaluating the characteristics of advanced high-performance concrete (HPC) is crucial. Machine learning techniques are widely recognized as competent tools for forecasting the mechanical characteristics of concrete substances. This research centers on the comparison of different algorithms, including the standalone Catboost Regression model (CAT), hybrid models that incorporate the CAT model along with two distinct optimization algorithms, namely Artificial Rabbits Optimization (ARO) and Honey Badger Algorithm (HBA), as well as an ensemble approach that combines CAT with the ARO-HBA ensemble optimization algorithm. Considering the results indicated by the R2 values, the CAHB model showed significantly better performance in predicting both CS (R2trainCAHB=0.996) and FS (R2trainCAHB=0.994). Furthermore, when examining statistical accuracy metrics such as RMSE and MAE, it became evident that CAHB performed significantly better than CAT in forecasting the mechanical properties of concrete.

Ant backbone phylogeny resolved by modelling compositional heterogeneity among sites in genomic data

Ants are the most ubiquitous and ecologically dominant arthropods on Earth, and understanding their phylogeny is crucial for deciphering their character evolution, species diversification, and biogeography. Although recent genomic data have shown promise in clarifying intrafamilial relationships across the tree of ants, inconsistencies between molecular datasets have also emerged. Here I re-examine the most comprehensive published Sanger-sequencing and genome-scale datasets of ants using model comparison methods that model among-site compositional heterogeneity to understand the sources of conflict in phylogenetic studies. My results under the best-fitting model, selected on the basis of Bayesian cross-validation and posterior predictive model checking, identify contentious nodes in ant phylogeny whose resolution is modelling-dependent. I show that the Bayesian infinite mixture CAT model outperforms empirical finite mixture models (C20, C40 and C60) and that, under the best-fitting CAT-GTR + G4 model, the enigmatic Martialis heureka is sister to all ants except Leptanillinae, rejecting the more popular hypothesis supported under worse-fitting models, that place it as sister to Leptanillinae. These analyses resolve a lasting controversy in ant phylogeny and highlight the significance of model comparison and adequate modelling of among-site compositional heterogeneity in reconstructing the deep phylogeny of insects.

Predicting maximum scour depth at sluice outlet: a comparative study of machine learning models and empirical equations

Estimating the maximum scour depth of sluice outlets is pivotal in hydrological engineering, directly influencing the safety and efficiency of water infrastructure. This research compared traditional empirical formulas with advanced machine learning (ML) algorithms, including RID, SVM, CAT, and XGB, utilizing experimental datasets from prior studies. Performance statistics highlighted the efficacy of the ML algorithms over empirical formulas, with CAT and XGB leading the way. Specifically, XGB demonstrated superiority with a correlation coefficient (CORR) of 0.944 and a root mean square error (RMSE) of 0.439. Following closely, the CAT model achieved a CORR of 0.940, and SVM achieved 0.898. For empirical formulas, although CORR values up to 0.816 and RMSE values of 0.799 can be obtained, these numbers are still lower than most ML algorithms. Furthermore, a sensitivity analysis underscored the densimetric Froude number (Fd) as the most crucial factor in ML models, with influences ranging from 0.839 in RID to 0.627 in SVM. Uncertainty in ML model estimates was further quantified using the Monte Carlo technique with 1,000 simulations on testing datasets. CAT and XGB have shown more stability than the other models in providing estimates with mean CORRs of 0.937 and 0.946, respectively. Their 95% confidence intervals (CIs) are [0.929–0.944] for CAT and [0.933–0.954] for XGB. These results demonstrated the potential of ML algorithms, particularly CAT and XGB, in predicting the maximum scour depth. Although these models offer high accuracy and higher 95% CI than others, the empirical formulas retain their relevance due to their simplicity and quick computation, which may still make them favored in certain scenarios.

Mesocarnivores den site selection in arid ecosystems; A case study of Rüppell's fox and sand cat in central Iran

Understanding the relationships between species and their pattern of coexistence is essential in conservation planning. Rüppell's fox and sand cat are two poorly known species of desert areas that coexist in most parts of the desert belt of Africa and the Middle East. However, their habitat selection in many parts of their distribution are unknown. In this research, using the data collected from a three-year monitoring plan, we investigated the relationship between the den sites of Rüppell's fox and sand cat and habitat variables based on the generalized linear mixed model (GLMM) method. The results showed that for Rüppell's foxes, only the density of rodent burrows had a significant and positive effect. In the sand cat model, in addition to prey, vegetation density (P-value < 0.05) and vegetation height (P-value < 0.10) had significantly positive effects and elevation had a significantly negative effect (P-value < 0.10). We found that the sand cat is more specialized in habitat selection and depends more on the habitat cover. While the Rüppell's fox chose a more diverse range of soil and vegetation classes, the sand cat selected its den sites exclusively in sandy loam soils with the predominant cover of Haloxylon spp. and Caligonum spp. Acting as a generalist species, Rüppell's fox displayed a more pronounced response to human presence and selected dens with a broader view of their surroundings. These findings enhance our understanding of mesocarnivore coexistence in desert regions and provide valuable insights for the conservation planning of these species.

A combination of β-hydroxybutyrate and citrate ameliorates disease progression in a rat model of polycystic kidney disease.

Our research has shown that interventions producing a state of ketosis are highly effective in rat, mouse, and cat models of polycystic kidney disease (PKD), preventing and partially reversing cyst growth and disease progression. The ketone β-hydroxybutyrate (BHB) appears to underlie this effect. In addition, we have demonstrated that naturally formed microcrystals within kidney tubules trigger a renoprotective response that facilitates tubular obstruction clearance in healthy animals but, alternatively, leads to cyst formation in PKD. The administration of citrate prevents microcrystal formation and slows PKD progression. Juvenile Cy/+ rats, a nonorthologous PKD model, were supplemented from 3 to 8 wk of age with water containing titrated BHB, citrate, or in combination to find minimal effective and optimal dosages, respectively. Adult rats were given a reduced BHB/citrate combination or equimolar control K/NaCl salts from 8 to 12 wk of age. In addition, adult rats were placed in metabolic cages following BHB, citrate, and BHB/citrate administration to determine the impact on mineral, creatinine, and citrate excretion. BHB or citrate alone effectively ameliorates disease progression in juvenile rats, decreasing markers of cystic disease and, in combination, producing a synergistic effect. BHB/citrate leads to partial disease regression in adult rats with established cystic disease, inhibiting cyst formation and kidney injury. BHB/citrate confers benefits via multiple mechanisms, increases creatinine and citrate excretion, and normalizes mineral excretion. BHB and citrate are widely available and generally recognized as safe compounds and, in combination, exhibit high promise for supporting kidney health in polycystic kidney disease.NEW & NOTEWORTHY Combining β-hydroxybutyrate (BHB) and citrate effectively slows and prevents cyst formation and expansion in young Cy/+ rats using less BHB and citrate than when used alone, demonstrating synergy. In adult rats, the combination causes a partial reversal of existing disease, reducing cyst number and cystic area, preserving glomerular health, and decreasing markers of kidney injury. Our results suggest a safe and feasible strategy for supporting kidney health in polycystic kidney disease (PKD) using a combination of BHB and citrate.

The study of the course of the infectious process in lungs of cats during experimental infection with SARS-CoV-2

Aim. To study and characterise the features of the course of coronavirus infection in a domestic cat model, as well as to assess the danger of SARSCoV-2 isolated in Russia for these animals based on the data obtained, with the possibility of extrapolating to wild felines.Material and Methods. For the study, model animals – Felis silvestris catus – were divided into 3 groups. The viral strain of SARS-Cov-2/human/RUS/Nsk-FRCFTM-1/2020 was cultivated on Vero E6 cell culture and then administered intranasally in a volume of 200 μl, 105TCID50/ml, to animals from the first and second groups. Model animals from the first group were euthanized and lung fragments were taken on 6–day post infection (d.p.i.), animals from the second group – on 14 d.p.i. The third group – the control group, was injected with saline in an equivalent volume. Histological sections colored with hematoxylin and eosin were investigated for pathomorphological changes in lung tissue using light microscopy.Results. According to the obtained results the pathomorphological picture in the lungs of experimental animals indicates the course of interstitial pneumonia for both 6 and 14 d.p.i. In addition, it has been determined that by 14 d.p.i. the growth of fibrous tissue in the lungs begins to be visualised, indicating the beginning of light regenerative processes.Conclusion. The study showed that cats are susceptible to the SARS-CoV-2 virus, and these model animals are characterized by the emergence of clinical manifestations and morphological patterns in the lungs, which correspond to interstitial pneumonia.

Effect of volume and methylene blue on fluorescence intensity and transit of indocyanine green for sentinel lymph node mapping in a simulated feline tumor model.

To compare the effect of volume and solution on transit time and fluorescence intensity (FI) using near-infrared fluorescence imaging (NIRF) in a simulated tumor model in cats. Secondarily, to describe SLN mapping with indocyanine green (ICG) NIRF and report any adverse effects of intradermally injected ICG in cats. 7 healthy purpose-bred domestic shorthaired male cats. Cats were randomly divided into 2 groups (ICG or ICG + methylene blue [MB]). Transit time and FI were determined for 1 or 2 mL solutions injected intradermally in 4 quadrants around a simulated tumor. Following massage, fluorescence intensity was quantified by calculating the corrected total ROI fluorescence using ImageJ software. Cats were monitored for adverse effects up to 4 weeks post-injection. A larger solution volume had decreased transit times to the SLN (P = .001). There was no significant difference in transit times between ICG and ICG-MB. ICG demonstrated a greater FI (P = .001) in the SLN compared to ICG-MB. Methylene blue did not percutaneously fluoresce under NIRF. The volume of the solution did not significantly affect FI. No adverse reactions were reported. Increased volume of ICG may aid in rapid percutaneous lymphatic tracking from tumor to SLN. Indocyanine green alone may be preferred over ICG-MB for greater visualization of the SLN. Intradermal injections of ICG and ICG-MB were well-tolerated in healthy cats with no significant complications. Clinical evaluation of this technique in an impaired lymphatic system, as seen in cancer patients, should be assessed in future research.

Neuromechanical Strategies for Obstacle Negotiation during Overground Locomotion following Incomplete Spinal Cord Injury in Adult Cats.

Following incomplete spinal cord injury in animals, including humans, substantial locomotor recovery can occur. However, functional aspects of locomotion, such as negotiating obstacles, remains challenging. We collected kinematic and electromyography data in 10 adult cats (5 males, 5 females) before and at weeks 1-2 and 7-8 after a lateral mid-thoracic hemisection on the right side of the cord while they negotiated obstacles of three different heights. Intact cats always cleared obstacles without contact. At weeks 1-2 after hemisection, the ipsilesional right hindlimb contacted obstacles in ∼50% of trials, triggering a stumbling corrective reaction or absent responses, which we termed Other. When complete clearance occurred, we observed exaggerated ipsilesional hindlimb flexion when crossing the obstacle with contralesional Left limbs leading. At weeks 7-8 after hemisection, the proportion of complete clearance increased, Other responses decreased, and stumbling corrective reactions remained relatively unchanged. We found redistribution of weight support after hemisection, with reduced diagonal supports and increased homolateral supports, particularly on the left contralesional side. The main neural strategy for complete clearance in intact cats consisted of increased knee flexor activation. After hemisection, ipsilesional knee flexor activation remained, but it was insufficient or more variable as the limb approached the obstacle. Intact cats also increased their speed when stepping over an obstacle, an increase that disappeared after hemisection. The increase in complete clearance over time after hemisection paralleled the recovery of muscle activation patterns or new strategies. Our results suggest partial recovery of anticipatory control through neuroplastic changes in the locomotor control system.SIGNIFICANCE STATEMENT Most spinal cord injuries (SCIs) are incomplete and people can recover some walking functions. However, the main challenge for people with SCIs that do recover a high level of function is to produce a gait that can adjust to everyday occurrences, such as turning, stepping over an obstacle, etc. Here, we use the cat model to answer two basic questions: How does an animal negotiate an obstacle after an incomplete SCI and why does it fail to safely clear it? We show that the inability to clear an obstacle is because of improper activation of muscles that flex the knee. Animals recover a certain amount of function thanks to new strategies and changes within the nervous system.

Salbutamol transport and deposition in healthy cat airways under different breathing conditions and particle sizes.

Salbutamol is a bronchodilatator commonly used for the treatment of feline inflammatory lower airway disease, including asthma or acute bronchospasm. As in humans, a pressurized metered dose inhaler (pMDI) is used in conjunction with a spacer and a spherical mask to facilitate salbutamol administration. However, efficacy of inhalation therapy is influenced by different factors including the non-cooperative character of cats. In this study, the goal was to use computational fluid dynamics (CFD) to analyze the impact of breathing patterns and salbutamol particle size on overall drug transport and deposition using a specific spherical mask and spacer designed for cats. A model incorporating three-dimensional cat airway geometry, a commercially available spherical mask, and a 10 cm spacer, was used for CFD analysis. Two peak inspiratory flows were tested: 30 mL/s and 126 mL/s. Simulations were performed with 30s breathing different inspiratory and expiratory times, respiratory frequencies and peaks. Droplet spray transport and deposition were simulated with different particle sizes typical of the drug delivery therapies (1, 5, 10, and 15 μm). The percentage of particle deposition into the device and upper airways decreased with increasing particle diameter during both flows imposed in this cat model. During increased mean ventilatory rate (MVR) conditions, most of the salbutamol was lost in the upper airways. And during decreased MVR conditions, most of the particles remained in suspension (still in hold-up) between the mask and the carina, indicating the need for more than 30 s to be transported. In both flows the percentage of particles traveling to the lung was low at 1.5%-2.3%. In conclusion, in contrast to what has been described in the human literature, the results from this feline model suggest that the percentage of particles deposited on the upper airway decreases with increasing particle diameter.

Epistemic uncertainty in catastrophe models—A base level examination

AbstractIn this paper, we evaluate sources of variation in the output from catastrophe models with emphasis on the epistemic uncertainty in modeled expected losses. Using building data from the 34 buildings that comprised the California Northridge campus at the time of the Northridge earthquake, we explore the sensitivity of estimated average annual losses obtained from a cat model to the quality of model input. Namely, we consider how changes in four key model assumptions—building locations, building height, construction type, and the event catalog—affect cat model loss estimates. We find that accurate information on some input variables is critical (e.g., all steel construction) and the interaction between input variables should not be discounted. Our results have important implications for insurer decisions that are informed by the output of catastrophe models—product pricing, portfolio diversification and underwriting decisions, negotiations and discussions with regulators and similar activities with capital market participants. The financial impact of improving data quality and targeting data related to key model inputs for that insurer when at scale is not trivial. As such, this paper provides an impetus for establishing and improving benchmarks for model inputs.

A remnant kidney surgery model in cats induces acute and chronic outcomes that mimic spontaneous chronic kidney disease.

To report acute and chronic outcomes of cats with chronic kidney disease (CKD) induced by a remnant kidney model. 32 purpose-bred cats (n = 15 female, n = 17 male). Cats underwent a 2-stage reduction in renal mass through partial arterial ligation of 1 kidney (day 28) and delayed contralateral nephrectomy (day 0), targeting an 11/12th functional nephrectomy. Acute (days -28 - 29) survival and renal function parameters were compared over time, and the latter were evaluated as predictors for acute mortality. Chronic (days 30 to >1,100) survival, renal function, and morphology were described. Acutely, renal function deteriorated in all cats (mean ± SD baseline and day 28 serum creatinine mean concentration, 1.13 ± 0.23 mg/dL and 3.03 ± 1.20 mg/dL, respectively; P < .001; and GFR, 3.22 mL/min/kg ± 0.12 and 1.21 mL/min/kg ± 0.08, respectively; P < .001). Seven (22%) cats were euthanized after because of clinical signs of uremia after contralateral nephrectomy. Prenephrectomy renal function tests were not significant indicators for survival during this acute phase. Twenty-five cats entered the chronic phase. Ten cats were euthanized at a median of 163 days from nephrectomy because of progressive renal dysfunction. Median survival times were significantly different when stratified by acute kidney injury grade at day 29. Cats in the chronic phase had clinical courses similar to cats with naturally occurring CKD, and most (13/15) were in CKD stage 2. The remnant kidney model is effective at reducing kidney function to an extent that mimics important characteristics of spontaneous CKD in cats.