Gut microbiota promoting propionic acid production accompanies caloric restriction-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for 7 days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during caloric restriction-induced weight loss (adjusted p < 0.05). Repeated measures correlation revealed the relative abundances of Prevotella 9 copri (correlation coefficient = 0.532, 95% CI (0.275, 0.717), p = 0.0002) significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during caloric restriction-induced weight loss.

The compounding effects of income loss and change in living arrangement on emerging adult women's mental health during COVID's onset.

Research suggests that young adult women were among those more susceptible to mental health declines in the initial months of COVID-19. Unfortunately, longitudinal data examining mental health before and after the pandemic's onset are extremely limited. In a sample of 240 women ages 18-29 who were surveyed online first in November-December 2019 and then again between May and July 2020, this study aimed to examine how major life changes associated with the pandemic (i.e. loss of income, loss of employment, change in relationship status, and change in living arrangement) impacted mental health (i.e. depression, anxiety, stress). Multivariate regression analyses were conducted on three models predicting stress, anxiety, and depression from the four life changes, controlling for the effects of mental health before the COVID-19 pandemic. Results showed that a change in living arrangement was uniformly associated with increased mental health problems among women who also experienced a decrease in income. Likewise, loss of income was uniformly related to increased mental health problems among women who also experienced a change in living arrangement. In contrast, job loss was associated with a decrease in stress, and changes in relationship status were not associated with mental health outcomes. These findings highlight the potential for COVID-19 to produce co-occurring and synergistic stressors. Meanwhile, the impact of job loss on mental health may have been attenuated by enhanced unemployment benefits. Mental health interventions that aim to support young women as the pandemic abates should be tailored to address the impact of multiple psychosocial stressors.

Gut microbiota promoting propionic acid production accompanies diet-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for seven days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during diet-induced weight loss (adjusted p < 0.05). Spearman correlation revealed the relative abundances of Prevotella 9 copri (ρ = 0.6385, p = 0.0006) and Blautia caecimuris (ρ = 0.5269, p = 0.0068) were significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during diet-induced weight loss.

The morphological and ecological variation of Arctostaphylos (Ericaceae) fruit: A link between plant ecology and animal foraging behavior.

Persistent soil seed banks are characteristic of Arctostaphylos (Ericaceae) species in the Mediterranean-climate California Floristic Province. While most species are obligate seeders, regeneration of stands of all Arctostaphylos species ultimately depends on post-fire seedling recruitment. Arctostaphylos seed banks are created, in large part, by scatter-hoarding rodents. Variation in fruit morphology, therefore, is expected to impact the Arctostaphylos-rodent interaction. Seeds produce sufficient rewards (nutritious mature embryo) to entice rodents to disperse and ultimately bury seeds in the soil. Hard seed coats increase the time required to extract the embryo, encouraging rodents to choose storage over immediate predation, and nutlets are frequently empty. We assessed the variation of fruit nutlet fusion and seed viability among 38 Arctostaphylos taxa. Factors such as latitude, elevation, life history, ploidy, and phylogenetic position were also analyzed. Generalized mixed-effects models were used to determine the factors contributing to variation in fruit nutlet fusion and seed viability. Our results indicate that fruit volume and shape are the most important variables affecting nutlet fusion and seed viability. Additionally, other potential influences only show a weak correlation and are not predicted to significantly impact nutlet fusion or seed viability. These findings provide insights into evolved strategies used by plants to increase reproductive success via scatter-hoarding rodents. Our study benefits the conservation and restoration of Arctostaphylos stands by emphasizing the importance of animal-mediated dispersal and providing estimates of seed viability for different species. With the anticipated effects of climate change, such as departures from historic fire regimes, the preservation of the relationship between plants and animal foragers is crucial for the continued survival of Arctostaphylos and California's evergreen chaparral.

Seed size-seed number trade-offs: influence of seed size on the density of fire-stimulated persistent soil seed banks.

PREMISE: Does the seed size-seed number allocation trade-off model apply to long-term persistent soil seed banks? This trade-off between seed size versus number of seeds produced is usually applied at a single population on an annual basis. Our question is how this model might apply to close relatives that produce dormant seed forming long-term persistent soil seed banks. These two criteria allow a focus on divergent evolution of conspecifics and permits us to isolate seed size in the spectrum of life history traits that may be influencing seed traits, and on how seed size influences accumulation and persistence in the soil. METHODS: In California, Arctostaphylos species only produce physiologically dormant seed that are fire-stimulated and that vary in seed size permitting seed size-seed bank density relationship as a test of the seed size-seed number allocation model. Soil seed banks of 10 species of Arctostaphylos were sampled with fruit volumes ranging from 21-1063 mm3 . Seed bank density was determined by hand extraction from soil samples. RESULTS: We found that seed bank densities were significantly negatively related to fruit or seed size. CONCLUSIONS: Rather than an issue of allocational trade-off between size and number, we interpret these results as reflecting seed predation and postfire seedling establishment. Seed bank densities, even after decades, generally were less than one or two-year's seed production, suggesting intense seed predation. Burial by scatter-hoarding rodents provided sufficient seeds deep enough for survival of fire. Variation on seed size suggests seedling establishment constraints, but it needs further research.

Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel-Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study.

PURPOSE: PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients. METHODS: Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes. RESULTS: Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort (n = 6). No significant reduction in affected tissue volume was observed (mean -4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement). CONCLUSION: Despite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.

Extended seed rain period of Adenostoma fasciculatum impacts diverse seed predators.

AIMS: The principal chaparral species in California, Adenostoma fasciculatum, an evergreen, sclerophyllous shrub, is broadly distributed and provides habitat and food resources for a large and diverse animal community. The effects of climate change, including elevated temperatures, fire frequency and severity, along with increased urban encroachment, have placed pressure on chaparral habitats in California. Our goal is to investigate aspects of reproductive ecology as a measure of the potential resiliency of A. fasciculatum. We focus on seed rain (all seed falling into the seed traps regardless of origin) and seed banks in the context of plant-animal interactions and regeneration. METHODS: Stand recovery following disturbance is achieved through both resprouting and germination from established persistent soil seed banks. In this study we focus on seed ecology using a series of experiments to document the length and quantity of seed rain, seed predation, parsing the importance of the community of granivores, and evaluating the connection between stand age and germination rate from soil seed banks. IMPORTANT FINDINGS: Our research documented an 8-month seed rain duration with over 1 million seeds per m2, multiple seed predators including passerines (songbirds) and rodents, and points to the possibility of native ants playing a role in the seed dispersal process. This is important given the recent advancement of the invasive Argentine ant (Linepthema humile) into Californian chaparral. This research demonstrates a clear relationship between A. fasciculatum and both resident and migratory granivores in the chaparral. We documented that a 39-year-old stand had higher germination rates than those which were 16, 20, 41 and 71 years old and how seed banks play a major role in assuring resiliency following fire. These findings are important for wildland managers to assure the continued resiliency of A. fasciculatum.

Commercial kefir products assessed for label accuracy of microbial composition and density.

Kefirs are fermented beverages containing yeast and bacteria produced by the fermentation of water or milk with kefir grains. Because microorganism density may influence a product's health benefits, label accuracy regarding viable bacterial density and taxonomy of fermented foods is important. In this study, the microbiota of 5 commercial kefir products were measured quantitatively using standard plating techniques and characterized using high-resolution, long-read 16S rRNA gene amplicon sequencing. To enumerate viable lactic acid bacteria, 2 lots of each product were plated on de Man, Rogosa and Sharpe agar upon opening and following 14 d and incubated under anaerobic and aerobic conditions. Results revealed that 66% of products with a guaranteed count of colony-forming units per gram overstated microorganism density by at least 1 log, with only product E exceeding 1 × 109 cfu/g. Sequencing results demonstrated moderate product label accuracy in regard to taxonomy, yet several products contained bacterial species above the minimum detectable threshold (0.001% relative abundance) that were not included on the labels (e.g., Streptococcus salivarius, Lactobacillus paracasei). Our results demonstrate a moderate level of labeling accuracy for commercial kefir products intended for human consumption. Regulatory agencies and consumers must continue to scrutinize these products and demand a higher level of accuracy and quality.

Allopatry, hybridization, and reproductive isolation in Arctostaphylos.

PREMISE: Hybridization plays a key role in introgressive adaptation, speciation, and adaptive radiation as a source of evolutionary innovation. Hybridization is considered common in Arctostaphylos, yet species boundaries are retained in stands containing multiple species. Arctostaphylos contains diploids and tetraploids, and recent phylogenies indicate two clades; we hypothesize combinations of these traits limit or promote hybridization rates. METHODS: We statistically analyzed co-occurrence patterns of species by clade membership and ploidy level from 87 random 0.1 ha plots. We sampled multiple sites to analyze for percent hybridization based on morphology. Finally, phenophases were analyzed by scoring herbarium sheets for a large number of taxa from both clades as well as tetraploids, and second, surveying three field sites over two years for divergence in phenological stages between co-occurring taxa. RESULTS: Most taxa in Arctostaphylos are allopatric relative to other congenerics. When two taxa co-occur, the patterns are a diploid with a tetraploid, or two diploids from different clades. When three taxa co-occur, the pattern is two diploids from different clades and a tetraploid. Field and herbarium data both indicate flowering phenology is displaced between diploids from the two clades; one of the diploid clades and tetraploids overlap considerably. CONCLUSIONS: The two deep clades in Arctostaphylos are genetically distant, with hybrids rare or non-existent when taxa co-occur. Reproductive isolation between clades is enhanced by displaced flowering phenology for co-occurring species. Within clades, taxa appear to have few reproductive barriers other than an allopatric distribution or different ploidy levels.

Acoustic shock: an update review.

BACKGROUND: This paper discusses the concept of acoustic shock based on a literature review and the results of our own research into cases seen in both clinical and medicolegal practice. With the demise of traditional 'metal bashing' and 'smoke stack' heavy industries, there has been a decline in the incidence of noise-induced hearing loss and tinnitus in this form of employment. However, with the increasing establishment of call centre work, the emergence of acoustic shock has been noted. Acoustic shock is recognised as a clinical entity distinct from noise-induced hearing loss and acoustic trauma. OBJECTIVE: This article discusses clinical implications, medicolegal considerations in light of a recent high-profile court case and proposed criteria for diagnosis.

Subspecies differentiation in an enigmatic chaparral shrub species.

PREMISE: Delimiting biodiversity units is difficult in organisms in which differentiation is obscured by hybridization, plasticity, and other factors that blur phenotypic boundaries. Such work is more complicated when the focal units are subspecies, the definition of which has not been broadly explored in the era of modern genetic methods. Eastwood manzanita (Arctostaphylos glandulosa Eastw.) is a widely distributed and morphologically complex chaparral shrub species with much subspecific variation, which has proven challenging to categorize. Currently 10 subspecies are recognized, however, many of them are not geographically segregated, and morphological intermediates are common. Subspecies delimitation is of particular importance in this species because two of the subspecies are rare. The goal of this study was to apply an evolutionary definition of "subspecies" to characterize structure within Eastwood manzanita. METHODS: We used publicly available geospatial environmental data and reduced-representation genome sequencing to characterize environmental and genetic differentiation among subspecies. In addition, we tested whether subspecies could be differentiated by environmentally associated genetic variation. RESULTS: Our analyses do not show genetic differentiation among subspecies of Eastwood manzanita, with the exception of one of the two rare subspecies. In addition, our environmental analyses did not show ecological differentiation, though limitations of the analysis prevent strong conclusions. CONCLUSIONS: Genetic structure within Eastwood manzanita does not correspond to current subspecies circumscriptions, but rather reflects geographic distribution. Our study suggests that subspecies concepts need to be reconsidered in long-lived plant species, especially in the age of next-generation sequencing.

Demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma: a UK population study.

OBJECTIVE: To investigate the demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma. DESIGN: A retrospective national population-based study. SETTING: UK 1995-2015. POPULATION: A total of 234 women with a diagnosis of gestational choriocarcinoma, in the absence of a prior molar pregnancy, managed at the UKs two gestational trophoblast centres in London and Sheffield. METHODS: Retrospective review of the patient's demographic and clinical data. Comparison with contemporary UK birth and pregnancy statistics. MAIN OUTCOMES: Incidence statistics for non-molar choriocarcinoma across the maternal age groups. Cure rates for patients by FIGO prognostic score group. RESULTS: Over the 21-year study period, there were 234 cases of non-molar gestational choriocarcinoma, giving an incidence of 1:66 775 relative to live births and 1:84 226 to viable pregnancies. For women aged under 20, the incidence relative to viable pregnancies was 1:223 494, for ages 30-34, 1:80 227, and for ages 40-45, 1:41 718. Treatment outcomes indicated an overall 94.4% cure rate. Divided by FIGO prognostic groups, the cure rates were low-risk group 100%, high-risk group 96% and ultra-high-risk group 80.5%. CONCLUSIONS: Non-molar gestational choriocarcinoma is a very rare diagnosis with little prior detailed information on the demographics and natural history. The data in this study give age-related incidence data based on a large national population study. The results also demonstrated the widely varying natural history of this rare malignancy and the marked correlation of disease incidence with rising maternal age. TWEETABLE ABSTRACT: National gestational choriocarcinoma database indicates a close association between increasing maternal age and incidence.

Influence of a climatic gradient on genetic exchange between two oak species.

PREMISE: In plant groups with limited intrinsic barriers to gene flow, it is thought that environmental conditions can modulate interspecific genetic exchange. Oaks are known for limited barriers to gene flow among closely related species. Here, we use Quercus as a living laboratory in which to pursue a fundamental question in plant evolution: Do environmental gradients restrict or promote genetic exchange between species? METHODS: We focused on two North American oaks, the rare Quercus dumosa and the widespread Q. berberidifolia. We sampled intensively along a contact zone in California, USA. We sequenced restriction site-associated DNA markers and measured vegetative phenotype. We tested for genetic exchange, the association with climate, and the effect on phenotype. RESULTS: There is evidence for genetic exchange between the species. Admixed plants are found in areas of intermediate climate, while less admixed plants are found at the extremes of the climatic gradient. Genetic and phenotypic patterns are out of phase in the contact zone; some plants display the phenotype of one species but are genetically associated with another. CONCLUSIONS: Our results support the hypothesis that a strong climatic gradient can promote genetic exchange between species. The overall weak correlation between genotype and phenotype in the contact zone between the species suggests that genetic exchange can lead to the breakdown of trait combinations used to define species. This incongruency predicts ongoing problems for conservation of Q. dumosa, with implications for conservation of other oaks.

Local patterns of diversity in California northern coastal scrub.

Within global biodiversity hotspots such as the California Floristic Province, local patterns of diversity must be better understood to prioritize conservation for the greatest number of species. This study investigates patterns of vascular plant diversity in relation to coast-inland environmental gradients in the shrublands of Central California known as northern coastal scrub. We sampled coastal shrublands of the San Francisco Bay Area at coastal and inland locations, modeled fine-scale climatic variables, and developed an index for local exposure to maritime salts. We compared diversity, composition, and structure of the coastal and inland plots using indirect gradient analysis and estimated species accumulation using rarefaction curves. Coastal plots were significantly higher in alpha, beta, and gamma diversity than inland plots. Plant diversity (effective species number) in coastal plots was 2.1 times greater than inland plots, and beta diversity was 1.9 times greater. Estimated richness by rarefaction was 2.05 times greater in coastal sites than inland sites. Salt deposition and water availability were the abiotic process most strongly correlated with increased maritime plant diversity and compositional differences. Stands of northern coastal scrub on the immediate coast with higher maritime influence exhibit markedly higher plant diversity than most interior stands, paralleling previous work in other vegetation types in this region. These studies suggest that the California coastline deserves special consideration for botanical conservation. Fine-scale climatic models of cloud frequency, water availability, and the salt deposition index presented here can be used to define priority areas for plant conservation in California and other coastal regions worldwide.

Collectively Improving Our Teaching: Attempting Biology Department-wide Professional Development in Scientific Teaching.

Many efforts to improve science teaching in higher education focus on a few faculty members at an institution at a time, with limited published evidence on attempts to engage faculty across entire departments. We created a long-term, department-wide collaborative professional development program, Biology Faculty Explorations in Scientific Teaching (Biology FEST). Across 3 years of Biology FEST, 89% of the department's faculty completed a weeklong scientific teaching institute, and 83% of eligible instructors participated in additional semester-long follow-up programs. A semester after institute completion, the majority of Biology FEST alumni reported adding active learning to their courses. These instructor self-reports were corroborated by audio analysis of classroom noise and surveys of students in biology courses on the frequency of active-learning techniques used in classes taught by Biology FEST alumni and nonalumni. Three years after Biology FEST launched, faculty participants overwhelmingly reported that their teaching was positively affected. Unexpectedly, most respondents also believed that they had improved relationships with departmental colleagues and felt a greater sense of belonging to the department. Overall, our results indicate that biology department-wide collaborative efforts to develop scientific teaching skills can indeed attract large numbers of faculty, spark widespread change in teaching practices, and improve departmental relations.

The effect of diet, adiposity, and weight loss on the secretion of incretin hormones in cats.

Degree of adiposity and dietary macronutrient composition affect incretin hormone secretion in humans and mice, but little is known about their effect in cats. In this study, 7 overweight cats were fed a maintenance diet (MD) for at least 2 wk followed by a reduced calorie diet (RCD), which was lower in fat and higher in carbohydrates and fiber. Cats were fed ad libitum initially, and then, food was restricted to achieve 1%-2% loss of body weight weekly (11 wk). When lean, cats were fed MD for 2 wk. A standardized meal test (SMT) using a third diet was performed after at least 7 d on each diet, before and after weight loss (four SMT's total). Glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) concentrations were measured immediately before and over 6 h after feeding the SMT. Area under the curve (AUC) was compared for GLP-1, GIP, and insulin concentrations using 2-way analysis of variance. Leaner cats had increased GIPAUC compared to obese cats (P = 0.025). There was a trend toward increased GIPAUC on RCD compared to the MD (P = 0.085). There was a moderate negative correlation between body fat percentage and GLP-1AUC (r = -0.45; P = 0.05). There was no effect of diet on GLP-1AUC. In conclusion, degree of adiposity and dietary macronutrient content could be important in determining GIP responses not only acutely but also on a long-term basis. Further investigation of GIP responses in cats should take both diet and degree of adiposity into account.

Atypical neurofibromatosis type 1 with unilateral limb hypertrophy mimicking overgrowth syndrome.

Neurofibromatosis type 1 (NF1; OMIM 162200), a dominantly inherited multitumor syndrome, results from mutations in the Neurofibromin 1 (NF1) gene. We present the case of a Hungarian woman with the clinical phenotype of NF1 over her whole body and the clinical features of unilateral overgrowth involving her entire left leg. This unusual phenotype suggested either the atypical form of NF1 or the coexistence of NF1 and overgrowth syndrome. Direct sequencing of the genomic DNA isolated from peripheral blood revealed a novel frameshift mutation (c.5727insT, p.V1909fsX1912) in the NF1 gene. Next-generation sequencing of 50 oncogenes and tumour suppressor genes, performed on the genomic DNAs isolated from tissue samples and peripheral blood, detected only wild-type sequences. Based on these results, we concluded that the patient is affected by an unusual phenotype of NF1, and that the observed unilateral overgrowth of the left leg might be a rare consequence of the identified c.5727insT mutation.

Classification systems in Gestational trophoblastic neoplasia - Sentiment or evidenced based?

The classification system for Gestational trophoblastic neoplasia (GTN) has proved a controversial topic for over 100years. Numerous systems simultaneously existed in different countries, with three main rival classifications gaining popularity, namely histological, anatomical and clinical prognostic systems. Until 2000, prior to the combination of the FIGO and WHO classifications, there was no worldwide consensus on the optimal classification system, largely due to a lack of high quality data proving the merit of one system over another. Remarkably, a validated, prospectively tested classification system is yet to be conducted. Over time, increasing criticisms have emerged regarding the currently adopted combined FIGO/WHO classification system, and its ability to identify patients most likely to develop primary chemotherapy resistance or disease relapse. This is particularly pertinent for patients with low-risk disease, whereby one in three patients are resistant to first line therapy, rising to four out of five women who score 5 or 6. This review aims to examine the historical basis of the GTN classification systems and critically appraise the evidence on which they were based. This culminates in a critique of the current FIGO/WHO prognostic system and discussion surrounding clinical preference versus evidence based practice.

Fibroblast Growth Factor-23 Concentration in Dogs with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with hyperphosphatemia, decreased vitamin D metabolite concentrations, and hyperparathyroidism. This syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is an early biomarker of CKD in people. It is an independent risk factor for both progression of renal disease and survival time in humans and cats with CKD. Information about FGF-23 in healthy dogs and those with CKD is lacking. OBJECTIVES: To measure FGF-23 concentration in dogs with different stages of CKD and determine its association with factors involved in CKD-MBD, including serum phosphorus and parathyroid hormone (PTH) concentrations. A secondary aim was to validate an ELISA for measurement of plasma FGF-23 concentration in dogs. ANIMALS: Thirty-two client-owned dogs with naturally occurring CKD and 10 healthy control dogs. METHODS: Prospective cross-sectional study. An FGF-23 ELISA was used to measure plasma FGF-23 concentration in dogs and their association with serum creatinine, phosphorus, calcium, and PTH concentrations. RESULTS: Plasma FGF-23 concentrations increased with severity of CKD and were significantly different between IRIS stages 1 and 2 versus stages 3 and 4 (P < .0001). Increases in FGF-23 concentrations were more frequent than hyperparathyroidism or hyperphosphatemia in this cohort. Serum creatinine and phosphorus concentrations were the strongest independent predictors of FGF-23 concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma FGF-23 concentrations increase in dogs with CKD as disease progresses. Plasma FGF-23 concentrations appear to be useful for further study of the pathophysiology of CKD-MBD in dogs.

Association of Vitamin D Metabolites with Parathyroid Hormone, Fibroblast Growth Factor-23, Calcium, and Phosphorus in Dogs with Various Stages of Chronic Kidney Disease.

BACKGROUND: Hypovitaminosis D is associated with progression of renal disease, development of renal secondary hyperparathyroidism (RHPT), chronic kidney disease-mineral bone disorder (CKD-MBD), and increased mortality in people with CKD. Despite what is known regarding vitamin D dysregulation in humans with CKD, little is known about vitamin D metabolism in dogs with CKD. OBJECTIVES: The purpose of our study was to further elucidate vitamin D status in dogs with different stages of CKD and to relate it to factors that affect the development of CKD-MBD, including parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), calcium, and phosphorus concentrations. METHODS: Thirty-seven dogs with naturally occurring CKD were compared to 10 healthy dogs. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and 24,25-dihydroxyvitamin D [24,25(OH)2 D], and PTH and FGF-23 concentrations were measured. Their association with serum calcium and phosphorus concentrations and IRIS stage was determined. RESULTS: Compared to healthy dogs, all vitamin D metabolite concentrations were significantly lower in dogs with International Renal Interest Society (IRIS) stages 3 and 4 CKD (r [creatinine]: -0.49 to -0.60; P < .05) but not different in dogs with stages 1 and 2 CKD. All vitamin D metabolites were negatively correlated with PTH, FGF-23, and phosphorus concentrations (r: -0.39 to -0.64; P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: CKD in dogs is associated with decreases in all vitamin D metabolites evaluated suggesting that multiple mechanisms, in addition to decreased renal mass, affect their metabolism. This information could have prognostic and therapeutic implications.