The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis.

Clonal haematopoiesis, which is highly prevalent in older individuals, arises from somatic mutations that endow a proliferative advantage to haematopoietic cells. Clonal haematopoiesis increases the risk of myocardial infarction and stroke independently of traditional risk factors1. Among the common genetic variants that give rise to clonal haematopoiesis, the JAK2V617F (JAK2VF) mutation, which increases JAK-STAT signalling, occurs at a younger age and imparts the strongest risk of premature coronary heart disease1,2. Here we show increased proliferation of macrophages and prominent formation of necrotic cores in atherosclerotic lesions in mice that express Jak2VF selectively in macrophages, and in chimeric mice that model clonal haematopoiesis. Deletion of the essential inflammasome components caspase 1 and 11, or of the pyroptosis executioner gasdermin D, reversed these adverse changes. Jak2VF lesions showed increased expression of AIM2, oxidative DNA damage and DNA replication stress, and Aim2 deficiency reduced atherosclerosis. Single-cell RNA sequencing analysis of Jak2VF lesions revealed a landscape that was enriched for inflammatory myeloid cells, which were suppressed by deletion of Gsdmd. Inhibition of the inflammasome product interleukin-1ß reduced macrophage proliferation and necrotic formation while increasing the thickness of fibrous caps, indicating that it stabilized plaques. Our findings suggest that increased proliferation and glycolytic metabolism in Jak2VF macrophages lead to DNA replication stress and activation of the AIM2 inflammasome, thereby aggravating atherosclerosis. Precise application of therapies that target interleukin-1ß or specific inflammasomes according to clonal haematopoiesis status could substantially reduce cardiovascular risk.

How Lazy Are Pet Cats Really? Using Machine Learning and Accelerometry to Get a Glimpse into the Behaviour of Privately Owned Cats in Different Households.

Surprisingly little is known about how the home environment influences the behaviour of pet cats. This study aimed to determine how factors in the home environment (e.g., with or without outdoor access, urban vs. rural, presence of a child) and the season influences the daily behaviour of cats. Using accelerometer data and a validated machine learning model, behaviours including being active, eating, grooming, littering, lying, scratching, sitting, and standing were quantified for 28 pet cats. Generalized estimating equation models were used to determine the effects of different environmental conditions. Increasing cat age was negatively correlated with time spent active (p < 0.05). Cats with outdoor access (n = 18) were less active in winter than in summer (p < 0.05), but no differences were observed between seasons for indoor-only (n = 10) cats. Cats living in rural areas (n = 7) spent more time eating than cats in urban areas (n = 21; p < 0.05). Cats living in single-cat households (n = 12) spent more time lying but less time sitting than cats living in multi-cat households (n = 16; p < 0.05). Cats in households with at least one child (n = 20) spent more time standing in winter (p < 0.05), and more time lying but less time sitting in summer compared to cats in households with no children (n = 8; p < 0.05). This study clearly shows that the home environment has a major impact on cat behaviour.

Smart capsules for sensing and sampling the gut: status, challenges and prospects.

Smart capsules are developing at a tremendous pace with a promise to become effective clinical tools for the diagnosis and monitoring of gut health. This field emerged in the early 2000s with a successful translation of an endoscopic capsule from laboratory prototype to a commercially viable clinical device. Recently, this field has accelerated and expanded into various domains beyond imaging, including the measurement of gut physiological parameters such as temperature, pH, pressure and gas sensing, and the development of sampling devices for better insight into gut health. In this review, the status of smart capsules for sensing gut parameters is presented to provide a broad picture of these state-of-the-art devices while focusing on the technical and clinical challenges the devices need to overcome to realise their value in clinical settings. Smart capsules are developed to perform sensing operations throughout the length of the gut to better understand the body's response under various conditions. Furthermore, the prospects of such sensing devices are discussed that might help readers, especially health practitioners, to adapt to this inevitable transformation in healthcare. As a compliment to gut sensing smart capsules, significant amount of effort has been put into the development of robotic capsules to collect tissue biopsy and gut microbiota samples to perform in-depth analysis after capsule retrieval which will be a game changer for gut health diagnosis, and this advancement is also covered in this review. The expansion of smart capsules to robotic capsules for gut microbiota collection has opened new avenues for research with a great promise to revolutionise human health diagnosis, monitoring and intervention.

Myeloid LXR (Liver X Receptor) Deficiency Induces Inflammatory Gene Expression in Foamy Macrophages and Accelerates Atherosclerosis.

BACKGROUND: Cholesterol loaded macrophage foam cells are a prominent feature of atherosclerotic plaques. Single-cell RNA sequencing has identified foam cells as TREM2 (triggering receptor expressed on myeloid cells 2) positive populations with low expression of inflammatory genes, resembling the TREM2 positive microglia of neurodegenerative diseases. Cholesterol loading of macrophages in vitro results in activation of LXR (liver X receptor) transcription factors and suppression of inflammatory genes. METHODS: To test the hypothesis that LXRs mediate anti-inflammatory effects in Trem2 expressing atherosclerotic plaque foam cells, we performed RNA profiling on plaque cells from hypercholesterolemic mice with myeloid LXR deficiency. RESULTS: Myeloid LXR deficiency led to a dramatic increase in atherosclerosis with increased monocyte entry, foam cell formation, and plaque inflammation. Bulk cell-RNA profiling of plaque myeloid cells showed prominent upregulation of inflammatory mediators including oxidative, chemokine, and chemotactic genes. Single-cell RNA sequencing revealed increased numbers of foamy TREM2-expressing macrophages; however, these cells had reduced expression of the Trem2 gene expression module, including phagocytic and cholesterol efflux genes, and had switched to a proinflammatory and proliferative phenotype. Expression of Trem2 was suppressed by inflammatory signals but not directly affected by LXR activation in bone marrow-derived macrophages. CONCLUSIONS: Our current studies reveal the key role of macrophage LXRs in promoting the Trem2 gene expression program and in suppressing inflammation in foam cells of atherosclerotic plaques.

The Use of Triaxial Accelerometers and Machine Learning Algorithms for Behavioural Identification in Domestic Cats (Felis catus): A Validation Study.

Animal behaviour can be an indicator of health and welfare. Monitoring behaviour through visual observation is labour-intensive and there is a risk of missing infrequent behaviours. Twelve healthy domestic shorthair cats were fitted with triaxial accelerometers mounted on a collar and harness. Over seven days, accelerometer and video footage were collected simultaneously. Identifier variables (n = 32) were calculated from the accelerometer data and summarized into 1 s epochs. Twenty-four behaviours were annotated from the video recordings and aligned with the summarised accelerometer data. Models were created using random forest (RF) and supervised self-organizing map (SOM) machine learning techniques for each mounting location. Multiple modelling rounds were run to select and merge behaviours based on performance values. All models were then tested on a validation accelerometer dataset from the same twelve cats to identify behaviours. The frequency of behaviours was calculated and compared using Dirichlet regression. Despite the SOM models having higher Kappa (>95%) and overall accuracy (>95%) compared with the RF models (64-76% and 70-86%, respectively), the RF models predicted behaviours more consistently between mounting locations. These results indicate that triaxial accelerometers can identify cat specific behaviours.

Lipid and metabolic syndrome traits in coronary artery disease: a Mendelian randomization study.

Mendelian randomization (MR) of lipid traits in CAD has provided evidence for causal associations of LDL-C and TGs in CAD, but many lipid trait genetic variants have pleiotropic effects on other cardiovascular risk factors that may bias MR associations. The goal of this study was to evaluate pleiotropic effects of lipid trait genetic variants and to account for these effects in MR of lipid traits in CAD. We performed multivariable MR using inverse variance-weighted and MR-Egger methods in large (n ≥ 300,000) GWAS datasets. We found that 30% of lipid trait genetic variants have effects on metabolic syndrome traits, including BMI, T2D, and systolic blood pressure (SBP). Nonetheless, in multivariable MR analysis, LDL-C, HDL-C, TGs, BMI, T2D, and SBP are independently associated with CAD, and each of these associations is robust to adjustment for directional pleiotropy. MR at loci linked to direct effects on HDL-C and TGs suggests locus- and mechanism-specific causal effects of these factors on CAD.

Anti-Inflammatory Effects of HDL (High-Density Lipoprotein) in Macrophages Predominate Over Proinflammatory Effects in Atherosclerotic Plaques.

OBJECTIVE: HDL (high-density lipoprotein) infusion reduces atherosclerosis in animal models and is being evaluated as a treatment in humans. Studies have shown either anti- or proinflammatory effects of HDL in macrophages, and there is no consensus on the underlying mechanisms. Here, we interrogate the effects of HDL on inflammatory gene expression in macrophages. Approach and Results: We cultured bone marrow-derived macrophages, treated them with reconstituted HDL or HDL isolated from APOA1Tg;Ldlr-/- mice, and challenged them with lipopolysaccharide. Transcriptional profiling showed that HDL exerts a broad anti-inflammatory effect on lipopolysaccharide-induced genes and proinflammatory effect in a subset of genes enriched for chemokines. Cholesterol removal by POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine) liposomes or ß-methylcyclodextrin mimicked both pro- and anti-inflammatory effects of HDL, whereas cholesterol loading by POPC/cholesterol-liposomes or acetylated LDL (low-density lipoprotein) before HDL attenuated these effects, indicating that these responses are mediated by cholesterol efflux. While early anti-inflammatory effects reflect reduced TLR (Toll-like receptor) 4 levels, late anti-inflammatory effects are due to reduced IFN (interferon) receptor signaling. Proinflammatory effects occur late and represent a modified endoplasmic reticulum stress response, mediated by IRE1a (inositol-requiring enzyme 1a)/ASK1 (apoptosis signal-regulating kinase 1)/p38 MAPK (p38 mitogen-activated protein kinase) signaling, that occurs under conditions of extreme cholesterol depletion. To investigate the effects of HDL on inflammatory gene expression in myeloid cells in atherosclerotic lesions, we injected reconstituted HDL into Apoe-/- or Ldlr-/- mice fed a Western-type diet. Reconstituted HDL infusions produced anti-inflammatory effects in lesion macrophages without any evidence of proinflammatory effects. CONCLUSIONS: Reconstituted HDL infusions in hypercholesterolemic atherosclerotic mice produced anti-inflammatory effects in lesion macrophages suggesting a beneficial therapeutic effect of HDL in vivo.

Wheat particle size, insoluble fibre sources and whole wheat feeding influence gizzard musculature and nutrient utilisation to different extents in broiler chickens.

A 21-day experiment was conducted to investigate the effects of wheat particle size, insoluble fibre source and whole wheat (WW) inclusion on the gizzard musculature, intestinal architecture and nutrient utilisation of broiler chickens. The following seven treatments, all in mash form, were tested: control diet using finely ground wheat (Fine); control diet using medium-ground wheat (Medium); control diet using coarsely ground wheat (Coarse); fine diet diluted with 10 g/kg lignocellulose (LC); fine diet diluted with 30 g/kg oat hulls (OH); fine diet diluted with 30 g/kg wood shavings (WS); and ground wheat in the fine diet replaced with 50 and 100 g/kg WW during the second (day 8-14) and third (day 15-21) weeks of the study respectively. Except for the LC diet, all treatments increased (p < 0.05) the thickness of the caudodorsal thick muscle of gizzard compared to the fine diet. The highest (p < 0.05) caudoventral thin and cranioventral thick muscle diameters in the gizzard walls were achieved with the OH and WS diets. Feeding OH, WS and WW diets improved (p < 0.05) starch digestibility compared with the fine diet, while medium, coarse and LC diets had no effect (p > 0.05). All diets containing fibre sources (LC, OH and WS) reduced (p < 0.05) the energy digestibility compared to the fine diet. Birds fed OH and WS diets gained the lowest (p < 0.05) weights. Feeding LC, OH, WS and WW diets increased (p < 0.05) the feed per gain compared with the fine diet. The current results suggest that there is a potential for coarse particles, insoluble fibre sources and WW feeding to improve the gizzard musculature and digestibility of some nutrients, with the effect being more pronounced with the inclusion of structural fibre sources.

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats.

OBJECTIVE: To assess the potential of a thermal carbon dioxide (CO2) laser to explore antinociception in pain-free cats. STUDY DESIGN: Experimental, prospective, blinded, randomized study. ANIMALS: Sixty healthy adult female cats with a (mean±standard deviation) weight of 3.3±0.6 kg. METHODS: Cats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg(-1); buprenorphine 20 µg kg(-1); medetomidine 2 µg kg(-1); tramadol 2 mg kg(-1), and ketoprofen 2 mg kg(-1). Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15-30, 30-45, 45-60, 60-75, 90-105 and 120-135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO2 laser. Within-treatment differences in response latency were assessed using Friedman's test. Differences amongst treatments were assessed using independent Kruskal-Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect. RESULTS: Cats treated with morphine (χ2=12.90, df=6, p=0.045) and tramadol (χ2=20.28, df=6, p=0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p<0.05) only for tramadol at 60-75 and 90-105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond. CONCLUSIONS AND CLINICAL RELEVANCE: The CO2 laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.

Using meta-analysis to understand the impacts of dietary protein and fat content on the composition of fecal microbiota of domestic dogs (Canis lupus familiaris): A pilot study.

The interplay between diet and fecal microbiota composition is garnering increased interest across various host species, including domestic dogs. While the influence of dietary macronutrients and their associated microbial communities have been extensively reviewed, these reviews are descriptive and do not account for differences in microbial community analysis, nor do they standardize macronutrient content across studies. To address this, a meta-analysis was performed to assess the impact of dietary crude protein ("protein") and dietary crude fat ("fat") on the fecal microbiota composition in healthy dogs. Sixteen publications met the eligibility criteria for the meta-analysis, yielding a final data set of 314 dogs. Diets were classed as low, moderate, high, or supra in terms of protein or fat content. Sequence data from each publication were retrieved from public databases and reanalyzed using consistent bioinformatic pipelines. Analysis of community diversity indices and unsupervised clustering of the data with principal coordinate analysis revealed a small effect size and complete overlap between protein and fat levels at the overall community level. Supervised clustering through random forest analysis and partial least squares-discriminant analysis indicated alterations in the fecal microbiota composition at a more individual taxonomic level, corresponding to the levels of protein or fat. The Prevotellaceae Ga6A1 group and Enterococcus were associated with increasing levels of protein, while Allobaculum and Clostridium sensu stricto 13 were associated with increasing levels of fat. Interestingly, the random forest analyses revealed that Sharpea, despite its low relative abundance in the dog's fecal microbiome, was primarily responsible for the separation of the microbiome for both protein and fat. Future research should focus on validating and understanding the functional roles of these relatively low-abundant genera.

Infant responsiveness, alertness, haemoglobin and growth in rural Sidama, Ethiopia.

Several recent studies have supported relations between infant behaviour (alertness and responsiveness) and nutrition in addition to investigating infant behaviour within the context of changes in iron status over time. Existing research is typically limited to the investigation of the effects of a single vitamin or mineral, and no studies have been found that examined the influence that early alertness and responsiveness have on growth in early infancy, despite the fact that relations between behaviour and nutritional status may be bidirectional. The current study used a sample of Ethiopian infants and investigated anthropometrics, haemoglobin, the frequency of alertness and the frequency of responsiveness at 6 and 9 months of age. Six-month weight-for-age predicted 9-month frequency of alertness, while 6-month haemoglobin predicted 9-month frequency of responsiveness. Compared with responsive infants, non-responsive infants at 6 months remained more non-responsive at 9 months, although weight-for-age for both groups converged at 9 months. Results support relations between nutrition and behaviour (alertness and responsiveness) and provide evidence of a potentially useful tool (the Laboratory Temperament Assessment Battery) that was adapted to evaluate these relations in Ethiopia.

Home stimulation, development, and nutritional status of children under 2 years of age in the highlands of Madagascar.

BACKGROUND: The Vakinankaratra region of Madagascar has a high burden of child undernutrition which, in addition to poor psychosocial stimulation, is a strong risk factor of poor child development. However, there are limited studies evaluating the relations between developmental deficits, child nutrition outcomes, and home stimulation in the region. The purpose of this study was to assess the development of children aged 11-13 months in relation to their nutritional status and to examine parental home stimulation attitudes and practices in the Vakinankaratra region. METHODS: Cognitive (n = 36), language (n = 36), motor (n = 36), and socioemotional (n = 76) development were assessed using the Bayley Scales of Infant and Toddler Development III. Household stimulation environment was evaluated using the family care indicators survey. Stunting (length-for-age z-score < - 2) and underweight (weight-for-age z-score < - 2) were determined using the 2006 WHO growth standards. Perceptions of and barriers to greater home stimulation for children were collected using focus group discussions among parents and in-depth interviews with community nutrition agents. RESULTS: Almost all mothers reported that parent-child interaction with talk and play was very important. Alarmingly high stunting rates (> 69%) were observed in this subsample. Limited time and tiredness were the major barriers to home stimulation mentioned by parents and confirmed by key informants. Children had a very limited variety of play materials, and most of the mothers used household objects (75%) and materials from outside the house (71%) as children's toys. Composite cognitive [mean (SD): 60 (10.3)], motor [61.9 (13.4)], language [62 (13.2)], and socioemotional [85.1 (17.9]) scores were low. Fine motor, cognitive, and receptive and expressive language scores were correlated [0.4 < r < 0.7, p < 0.05]. CONCLUSIONS: The very high stunting rates and very low performance on cognitive, motor, language, and socioemotional development assessments of children in the Vakinankaratra region require urgent attention.

Prolonged glucocorticoid administration affects oocyte morphology in cats (Felis catus) undergoing an ovarian stimulation protocol.

While captivity-related stress and the associated rise in baseline glucocorticoid (GC) concentrations have been linked to ovarian quiescence in some felid species, no study has examined the effects of elevated GC on oocyte quality. This study examined the effects of exogenous GC administration on the ovarian response and oocyte quality of domestic cats after an ovarian stimulation protocol. Entire mature female cats were divided into treatment (n = 6) and control (n = 6) groups. Cats in the GC treatment (GCT) group were given 1 mg kg-1 oral prednisolone daily from Day 0-45. All cats (n = 12) were given 0.088 mg kg-1 day-1 progesterone orally from Day 0-37, before treatment with 75 IU eCG im to induce follicular growth on Day 40, followed by 50 IU hCG im 80 h later to induce ovulation. Cats were ovariohysterectomised 30 h after the hCG treatment. Blood samples were collected on Days 0, 10, 30 and 40 (prior to eCG treatment), 80 h after eCG treatment, and on Day 45 for cortisol, glucose, prednisolone, oestradiol, and progesterone analysis. Cortisol concentrations did not differ between treatment groups throughout the study. Mean glucose concentrations were higher in the GCT cats (P = 0.004). Prednisolone was undetectable in all samples. Oestradiol and progesterone concentrations confirmed that the eCG treatment stimulated follicular activity and ovulation in all cats. Following ovariohysterectomy, the ovarian responses were graded (1 = excellent, 4 = poor) and oocytes retrieved from the oviducts. Each oocyte was given a total oocyte score (TOS: using an 9-point scale, 8 = best) based on four parameters: oocyte morphology, size, ooplasm uniformity and granularity, and zona pellucida (ZP) thickness and variation. Ovulation was confirmed in all cats, with a mean of 10.5 ± 1.1 ovulations per cat. Ovarian mass, ovarian response, number of ovulations, and oocyte recovery did not differ between groups. Oocyte diameter did not differ between the groups, but the ZP was thinner in the GCT group (3.1 ± 0.3 µm vs. 4.1 ± 0.3 µm, P = 0.03). The TOS was similar between treatment and control cats, but the ooplasm grade was lower (1.5 ± 0.1 vs. 1.9 ± 0.1, P = 0.01) and there was a tendency for ZP grade to be poorer (0.8 ± 0.1 vs. 1.2 ± 0.2; P = 0.08) in the treatment group. In conclusion, the GC treatment resulted in morphological changes to oocytes collected following ovarian stimulation. Whether these changes would affect fertility warrants further investigation.

Drivers of Palatability for Cats and Dogs-What It Means for Pet Food Development.

The pet food industry is an important sector of the pet care market that is growing rapidly. Whilst the number of new and innovative products continues to rise, research and development to assess product performance follows traditional palatability methodology. Pet food palatability research focuses on the amount of food consumed through use of one-bowl and two-bowl testing, but little understanding is given to why differences are observed, particularly at a fundamental ingredient level. This review will highlight the key differences in feeding behaviour and nutritional requirements between dogs and cats. The dominant pet food formats currently available and the ingredients commonly included in pet foods are also described. The current methods used for assessing pet food palatability and their limitations are outlined. The opportunities to utilise modern analytical methods to identify complete foods that are more palatable and understand the nutritional factors responsible for driving intake are discussed.

Interactive relations among maternal depressive symptomatology, nutrition, and parenting.

Theoretical models linking maternal nutrition, depressive symptomatology, and parenting are underdeveloped. However, existing literature suggests that iron status and depressive symptomatology interact in relation to problematic parenting styles (authoritarian, permissive). Therefore, in the current study the authors investigate these interactive relations in a sample of breastfeeding mothers (n = 105) interviewed at three months postpartum. Participants completed questionnaires (from December 2008 to January 2011) regarding their depressive symptomatology and parenting styles. Iron status (i.e., hemoglobin, soluble transferrin receptors, and serum ferritin concentrations) was assessed from blood samples. Significant interactions were found between iron status and depressive symptomatology in relation to authoritarian parenting style (low warmth, high punishment and directiveness). For those women with hemoglobin below 14.00 g/dL, depressive symptomatology was positively related to authoritarian parenting style (p < 0.001). Thus, screening for poor iron status and depressive sympatomology in postpartum women may help to identify those at risk for problematic parenting. Dietary interventions may help to eliminate relations between depressive symptoms and problematic parenting.

Polymicrobial bacteraemia with Clostridioides difficile and Pseudomonas aeruginosa in an elderly man following antibiotic use.

Clostridioides difficile is a micro-organism well known to cause pseudomembranous colitis with rare extraintestinal manifestations. We present the case of an elderly male with multiple comorbidities who presented with acute onset of fever/chills and hypotension, found to have polymicrobial bacteraemia with C. difficile and Pseudomonas aeruginosa He was treated with piperacillin/tazobactam for P. aeruginosa bacteraemia, oral vancomycin for C. difficile colitis and intravenous, followed by oral metronidazole for C. difficile bacteraemia. Pseudomonas cleared after 1 day, and Clostridioides cleared after 4 days. Following an initial septic presentation, he responded appropriately to antimicrobial therapy and did well in follow-up.

Accelerometry and infrared thermography show potential for assessing ovarian activity in domestic cats (Felis catus).

Accurate and reliable monitoring of ovarian activity is challenging in many felids as current methods are either invasive or not amenable to real-time assessments. This 45-day study assessed whether accelerometry and infrared (IR) thermography can be used to address these limitations. Intact female domestic cats (n = 12) were given 0.088 mg kg-1 day-1 altrenogest (progestin) orally for 37 days to suppress follicular growth. On Day 40, cats were given 75 IU eCG im to induce follicular growth and 50 IU hCG im 80 h later to induce ovulation. Cats were ovariohysterectomised 30-31 h after the hCG treatment. Actical® accelerometers were fitted to the cats' collars and activity monitored continuously from the start of the altrenogest treatment until ovariohysterectomy. Infrared images of the perivulvar, perianal, and gluteal area were taken of each cat on Day 30 and daily from Days 36-45 of the study. Perivulvar temperature (PVT), PVT relative to gluteal temperatures (PVT-GT), and PVT relative to perianal temperature (PVT-PAT) were recorded for each image. Blood samples were collected on Days 0, 10, 30, and 40, immediately prior to the hCG treatment, and at the time of ovariohysterectomy. Serum oestradiol and progesterone concentrations indicated complete ovarian suppression by Day 30 and, together with morphological assessment of the ovaries, confirmed the induction of follicular growth and ovulation in all cats. Daily activity counts differed among cats (P < 0.001), so the daily activity counts of each cat were converted to a proportional change from the average daily activity count from Days 30-39 (defined as the 'proportional daily activity'). Proportional daily activity counts increased after the stimulation of follicular growth with eCG, with peak levels (2.03 ± 0.29-fold higher than pre-treatment levels; P = 0.006) occurring three days after the eCG treatment. The PVT-GT showed the greatest sensitivity to detect subtle changes in body temperature, increasing from early to late follicular growth (1.96 ± 0.33 °C increase from Day 41-43; P < 0.001) and decreasing after hCG-induced ovulation (1.24 ± 0.41 °C decrease from Day 43-45; P = 0.01). In conclusion, both accelerometry and IR thermography show potential as non-invasive, real-time methods for assessing ovarian activity in cats, but further research is required to determine if these methods could be used to monitor natural/non-stimulated oestrous cycles.

Exogenous glucocorticoid treatment affects Sertoli cell load and epididymal sperm quality in domestic cats (Felis catus).

Elevated glucocorticoid (GC) concentrations associated with captivity-related stress have been linked to impaired testicular function and low sperm quality in felids, but direct physiological evidence is lacking. This study assessed the effects of exogenous GC treatment on felid testicular function using the domestic cat (Felis catus) as a model species. Sixteen intact male cats aged 2.4 ± 0.8 years (mean ± SEM) were divided randomly into treatment (n = 8) and control (n = 8) groups. Treatment cats were given 1 mg kg-1 oral prednisolone daily for 50 days. Blood samples were taken on Days 0 (first prednisolone treatment), 2, 4, 7, 10, 20, 30, 40, 50 (prior to neutering) and 60 of the trial. All cats were orchiectomised on day 50, epididymal sperm assessed, and the testes fixed for histological assessment. Testosterone concentrations did not differ between the two groups. While sperm motility was similar between the treatment and control groups, cats given prednisolone had a higher proportion of morphologically abnormal sperm in both the caput (72.5% vs. 59.6%, P < 0.001) and cauda (56.7% vs. 35.8%, P < 0.001) epididymis. Testicular histomorphometric data and total number of germ cells per seminiferous tubule cross section did not differ between groups, nor did the relative abundance of spermatogonia, spermatocytes, and spermatids. Cats given prednisolone had fewer Sertoli cells per tubule cross-section than those in the control group (17.1 ± 0.9 vs. 19.7 ± 0.8, P = 0.04), which was likely related to higher rates of Sertoli cell apoptosis in treatment versus control cats (0.25 ± 0.02 vs. 0.10 ± 0.02 apoptotic Sertoli cells per tubule, respectively; P < 0.001). Sertoli cell load (number of germ cells per Sertoli cell) was also higher in the treatment group than in the control group (11.5 ± 0.8 vs. 9.4 ± 1.2 germ cells per Sertoli cell, respectively; P < 0.001), and was positively correlated with the percentage of morphologically abnormal sperm in the epididymis (r2 = 0.78, P < 0.001). Prednisolone treatment resulted in an increase in the proportion of abnormal sperm in the epididymis, which may be explained by an increased nurturing demand on a reduced Sertoli cell population. These findings provide novel evidence to support the hypothesis that elevated GC concentrations, such as those resulting from captivity-related stress, have the potential to impair testicular function and sperm quality in felids.

Addressing dyslipidemic risk beyond LDL-cholesterol.

Despite the success of LDL-lowering drugs in reducing cardiovascular disease (CVD), there remains a large burden of residual disease due in part to persistent dyslipidemia characterized by elevated levels of triglyceride-rich lipoproteins (TRLs) and reduced levels of HDL. This form of dyslipidemia is increasing globally as a result of the rising prevalence of obesity and metabolic syndrome. Accumulating evidence suggests that impaired hepatic clearance of cholesterol-rich TRL remnants leads to their accumulation in arteries, promoting foam cell formation and inflammation. Low levels of HDL may associate with reduced cholesterol efflux from foam cells, aggravating atherosclerosis. While fibrates and fish oils reduce TRL, they have not been uniformly successful in reducing CVD, and there is a large unmet need for new approaches to reduce remnants and CVD. Rare genetic variants that lower triglyceride levels via activation of lipolysis and associate with reduced CVD suggest new approaches to treating dyslipidemia. Apolipoprotein C3 (APOC3) and angiopoietin-like 3 (ANGPTL3) have emerged as targets for inhibition by antibody, antisense, or RNAi approaches. Inhibition of either molecule lowers TRL but respectively raises or lowers HDL levels. Large clinical trials of such agents in patients with high CVD risk and elevated levels of TRL will be required to demonstrate efficacy of these approaches.

In Vitro Assessment of Hydrolysed Collagen Fermentation Using Domestic Cat (Felis catus) Faecal Inocula.

The gastrointestinal microbiome has a range of roles in the host, including the production of beneficial fermentation end products such as butyrate, which are typically associated with fermentation of plant fibres. However, domestic cats are obligate carnivores and do not require carbohydrates. It has been hypothesised that in the wild, collagenous parts of prey-the so-called animal-derived fermentable substrates (ADFS) such as tendons and cartilage-may be fermented by the cat's gastrointestinal microbiome. However, little research has been conducted on ADFS in the domestic cat. Faecal inoculum was obtained from domestic cats either consuming a high carbohydrate (protein:fat:carbohydrate ratio of 35:20:28 (% dry matter basis)) or high protein (protein:fat:carbohydrate ratio of 75:19:1 (% dry matter basis)) diet. ADFS (hydrolysed collagen, cat hair, and cartilage) were used in a series of static in vitro digestions and fermentations. Concentrations of organic acids and ammonia were measured after 24 h of fermentation, and the culture community of microbes was characterised. The type of inoculum used affected the fermentation profile produced by the ADFS. Butyrate concentrations were highest when hydrolysed collagen was fermented with high protein inoculum (p < 0.05). In contrast, butyrate was not detectable when hydrolysed collagen was fermented in high carbohydrate inoculum (p < 0.05). The microbiome of the domestic cat may be able to ferment ADFS to provide beneficial concentrations of butyrate.