Developing diagnostic tools for canine periodontitis: combining molecular techniques and machine learning models.

BACKGROUND: Dental plaque microbes play a key role in the development of periodontal disease. Numerous high-throughput sequencing studies have generated understanding of the bacterial species associated with both canine periodontal health and disease. Opportunities therefore exist to utilise these bacterial biomarkers to improve disease diagnosis in conscious-based veterinary oral health checks. Here, we demonstrate that molecular techniques, specifically quantitative polymerase chain reaction (qPCR) can be utilised for the detection of microbial biomarkers associated with canine periodontal health and disease. RESULTS: Over 40 qPCR assays targeting single microbial species associated with canine periodontal health, gingivitis and early periodontitis were developed and validated. These were used to quantify levels of the respective taxa in canine subgingival plaque samples collected across periodontal health (PD0), gingivitis (PD1) and early periodontitis (PD2). When qPCR outputs were compared to the corresponding high-throughput sequencing data there were strong correlations, including a periodontal health associated taxa, Capnocytophaga sp. COT-339 (rs =0.805), and two periodontal disease associated taxa, Peptostreptococcaceae XI [G-4] sp. COT-019 (rs=0.902) and Clostridiales sp. COT-028 (rs=0.802). The best performing models, from five machine learning approaches applied to the qPCR data for these taxa, estimated 85.7% sensitivity and 27.5% specificity for Capnocytophaga sp. COT-339, 74.3% sensitivity and 67.5% specificity for Peptostreptococcaceae XI [G-4] sp. COT-019, and 60.0% sensitivity and 80.0% specificity for Clostridiales sp. COT-028. CONCLUSIONS: A qPCR-based approach is an accurate, sensitive, and cost-effective method for detection of microbial biomarkers associated with periodontal health and disease. Taken together, the correlation between qPCR and high-throughput sequencing outputs, and early accuracy insights, indicate the strategy offers a prospective route to the development of diagnostic tools for canine periodontal disease.

Umami taste perception and preferences of the domestic cat (Felis catus), an obligate carnivore.

The domestic cat (Felis catus) is an obligate carnivore, and as such has a meat-based diet. Several studies on the taste perception of cats have been reported, indicating that their sense of taste has evolved based on their carnivorous diet. Here, we propose that umami (mediated by Tas1r1-Tas1r3) is the main appetitive taste modality for the domestic cat by characterizing the umami taste of a range of nucleotides, amino acids, and their mixtures for cats obtained using complementary methods. We show for the first time that cats express Tas1r1 in taste papillae. The cat umami receptor responds to a range of nucleotides as agonists, with the purine nucleotides having the highest activity. Their umami receptor does not respond to any amino acids alone; however, 11 l-amino acids with a range of chemical characteristics act as enhancers in combination with a nucleotide. l-Glutamic acid and l-Aspartic acid are not active as either agonists or enhancers of the cat umami receptor due to changes in key binding residues at positions 170 and 302. Overall, cats have an appetitive behavioral response for nucleotides, l-amino acids, and their mixtures. We postulate that the renowned palatability of tuna for cats may be due, at least in part, to its specific combination of high levels of inosine monophosphate and free l-Histidine that produces a strong synergistic umami taste enhancement. These results demonstrate the critical role that the umami receptor plays in enabling cats to detect key taste compounds present in meat.

Bitter taste sensitivity in domestic dogs (Canis familiaris) and its relevance to bitter deterrents of ingestion.

As the most favoured animal companion of humans, dogs occupy a unique place in society. Understanding the senses of the dog can bring benefits to both the dogs themselves and their owners. In the case of bitter taste, research may provide useful information on sensitivity to, and acceptance of, diets containing bitter tasting materials. It may also help to protect dogs from the accidental ingestion of toxic substances, as in some instances bitter tasting additives are used as deterrents to ingestion. In this study we examined the receptive range of dog bitter taste receptors (Tas2rs). We found that orthologous dog and human receptors do not always share the same receptive ranges using in vitro assays. One bitter chemical often used as a deterrent, denatonium benzoate, is only moderately active against dTas2r4, and is almost completely inactive against other dog Tas2rs, including dTas2r10, a highly sensitive receptor in humans. We substituted amino acids to create chimeric dog-human versions of the Tas2r10 receptor and found the ECL2 region partly determined denatonium sensitivity. We further confirmed the reduced sensitivity of dogs to this compound in vivo. A concentration of 100µM (44.7ppm) denatonium benzoate was effective as a deterrent to dog ingestion in a two-bottle choice test indicating higher concentrations may increase efficacy for dogs. These data can inform the choice and concentration of bitter deterrents added to toxic substances to help reduce the occurrence of accidental dog poisonings.

A transcriptomic atlas of mammalian olfactory mucosae reveals an evolutionary influence on food odor detection in humans.

The mammalian olfactory system displays species-specific adaptations to different ecological niches. To investigate the evolutionary dynamics of olfactory sensory neuron (OSN) subtypes across mammalian evolution, we applied RNA sequencing of whole olfactory mucosa samples from mouse, rat, dog, marmoset, macaque, and human. We find that OSN subtypes, representative of all known mouse chemosensory receptor gene families, are present in all analyzed species. Further, we show that OSN subtypes expressing canonical olfactory receptors are distributed across a large dynamic range and that homologous subtypes can be either highly abundant across all species or species/order specific. Highly abundant mouse and human OSN subtypes detect odorants with similar sensory profiles and sense ecologically relevant odorants, such as mouse semiochemicals or human key food odorants. Together, our results allow for a better understanding of the evolution of mammalian olfaction in mammals and provide insights into the possible functions of highly abundant OSN subtypes.

Comparison of the alternative models SOURCE and SWAT for predicting catchment streamflow, sediment and nutrient loads under the effect of land use changes.

Quantifying the water quantity and quality variations resulting from human induced activities is important for policy makers in view of increasing water scarcity and water pollution. Simple models can be robust tools in estimating the runoff from catchments, but do they also sufficiently reflect complex physio-chemical processes required for spatially-explicit simulation of soil-water interactions, and the resulting pollutant responses in catchments? Do these models respond sensitive to the impacts of different land use change representations? These questions are considered by applying the semi-distributed process-based catchment models SWAT and SOURCE to the Sixth Creek catchment in South Australia. Both models used similar data whereas inputs for SOURCE were generated from land-use based Functional Units (FUs), while FUs for SWAT were based on land use, soil and slope combinations. After satisfying calibration of both models for the outlet station of the catchment, the simulated flow by SOURCE produced high goodness of fit metrics, while nutrient loads simulated by SWAT were more realistic. Both models benefitted from using locally available Potential Evapotranspiration data for calibrating the hydrology. Scenarios of intensified land uses by two models showed more credible results for sediment and nutrient loads with the static approach when simulating the linear rather than the non-linear land use changes. The study has shown that informing decisions on the hydrology at catchment scale is well suited to less-complex models, whereas decisions on impact of land use change on water quality in catchments are better suited by models with process descriptions for soil-water interactions.

The role of cardiac output monitoring in obstetric anesthesia.

PURPOSE OF REVIEW: Haemodynamic monitoring in obstetric patients has evolved during the last decade, with the development of minimally invasive and noninvasive continuous cardiac output (CO) monitors. This review focuses on recent articles that improve our understanding of physiology and haemodynamic changes during spinal anaesthesia in healthy pregnant women, and pathophysiology in women with preeclampsia and other cardiovascular disease. RECENT FINDINGS: Recent research findings in healthy women focus on the haemodynamic changes due to aortocaval compression, fluid administration, vasopressor therapy, and oxytocin during spinal anaesthesia for caesarean delivery. In preeclampsia, the haemodynamics of early versus late-onset disease and fluid management have been the subject of considerable investigation. Case reports suggest that invasive monitoring in combination with echocardiography is preferable for clinical management of high-risk obstetrics cases with unstable haemodynamics. SUMMARY: In healthy women, left lateral tilt remains an important clinical intervention during caesarean delivery, and phenylephrine is an essential early adjunct to fluid therapy. Noradrenaline may have a clinical benefit in selected patients. Carbetocin has similar haemodynamic effects to oxytocin. Haemodynamic changes associated with delivery per se may be minor compared with those due to oxytocin. Uncomplicated severe preeclampsia is usually associated with a normal to raised CO. Early-onset preeclampsia may be associated with more vasoconstriction and lower CO than late-onset disease. Passive leg raising may be useful to judge fluid responsiveness, and lung ultrasound may predict pulmonary oedema in preeclampsia. Further research is warranted to study the area of circulatory changes during delivery and the postpartum period, in healthy and preeclamptic women.

Characterization of beta-lactamases responsible for resistance to extended-spectrum cephalosporins in Escherichia coli and Salmonella enterica strains from food-producing animals in the United Kingdom.

Nine epidemiologically unrelated isolates [1 Salmonella Bredeney from turkeys, and 8 Escherichia coli [3 environmental isolates (2 from chickens, 1 from pigs), and 5 isolates from cattle with neonatal diarrhea]] were examined both pheno- and genotypically for extended-spectrum beta-lactam (ESBL) resistance. Resistance phenotypes (ampicillin, aztreonam, cefotaxime, cefpodoxime, ceftazidime, and ceftriaxone) suggested the presence of an ESBL enzyme, but cefoxitin MICs (>/= 32 mg/L) suggested the presence of an AmpC-like enzyme. Synergism experiments with benzo(b)thiophene-2-boronic acid (BZBTH2B) and isoelectric focusing (IEF) revealed the presence of an AmpC beta-lactamase with a pI >/= 9. amp C multiplex PCR, sequence, and Southern analyses indicated that only the Salmonella isolate had a plasmid-encoded AmpC beta-lactamase CMY-2 on a nonconjugative 60-MDa plasmid. PCR and sequence analysis of the E. coli ampC promoter identified mutations at positions -88(T), -82(G), -42(T), -18(A), -1(T) and +58(T) in all the isolates. In addition one strain had two extra-mutations at positions +23(A) and +49(G), and another strain had one extra-mutation at position +32(A). DNA fingerprinting revealed that all the E. coli isolates were different clones. It also showed that the U.K. Salmonella isolate was indistinguisable from a Canadian Salmonella isolate from turkeys; both had identical resistance phenotypes and produced CMY-2. This is the first report of a CMY-2 Salmonella isolate in the United Kingdom. These data imply that beta-lactam resistance in animal isolates can be generated de novo as evidenced by the E. coli strains, or in the case of the Salmonella strains be the result of intercontinental transmission due to an acquired resistance mechanism.

Antihypertensive medications and renal disease.

Patients with ESRD are likely to have hypertension as a comorbid condition. The management of hypertension must involve nonpharmacologic as well as pharmacologic treatment. In most cases, nonpharmacologic treatment, including severe sodium restriction, smoking cessation, elimination of alcohol intake, and weight reduction, can significantly lower blood pressure in the ESRD patient. If these methods remain insufficient, then a variety of pharmacologic treatment options exist, with ACE inhibitors and diuretics being the most common medical agents employed. Treating hypertension in this patient population, while extremely challenging, greatly reduces the risk of developing cardiac disease, thereby, reducing the risk of mortality.