Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis.

Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of ß-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gs-coupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.

The obesity-linked human lncRNA AATBC stimulates mitochondrial function in adipocytes.

Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, thermogenic adipocytes are linked to cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this plasticity could help improving metabolism. Here, we show that the lncRNA Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Comparing transcriptional profiles of human adipose tissues and cultured adipocytes we discovered that AATBC was enriched in thermogenic conditions. Using primary and immortalized human adipocytes we found that AATBC enhanced the thermogenic phenotype, which was linked to increased respiration and a more fragmented mitochondrial network. Expression of AATBC in adipose tissue of mice led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, BMI, and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.

Similar Insulin Regulation of Splanchnic FFA and VLDL-TG in Men with Nonalcoholic Hepatic Steatosis and Steatohepatitis.

This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis vs. steatohepatitis (NASH) in splanchnic and hepatic FFA and VLDL-triglycerides (VLDL-TG) balances. The study involved 17 obese men with biopsy-proven NAFLD (9 with NASH and 8 with simple steatosis). We used hepatic vein catheterization in combination with [3H]palmitate and [14C]VLDL-TG tracers to measure splanchnic palmitate and VLDL-TG uptake and release rates during basal and hyperinsulinemic conditions. Indocyanine green was used to measure splanchnic plasma flow. Splanchnic palmitate uptake was similar in the two groups and significantly reduced during hyperinsulinemia (NASH: 62 (48-77) vs. 38 (18-58) µmol/min; simple steatosis: 62 (46-78) vs. 45 (25-65) µmol/min, mean (95% CI), basal vs. clamp periods, respectively, p = 0.02 time-effect). Splanchnic palmitate release was also comparable between groups and non-significantly diminished during hyperinsulinemia. The percent palmitate delivered to the liver originating from visceral adipose tissue (VAT) lipolysis was similar and unchanged by hyperinsulinemia. Splanchnic uptake and release of VLDL-TG were similar between groups. Hyperinsulinemia suppressed VLDL-TG release (p <0.05 time-effect) in both groups. Insulin mediated glucose disposal was similar in the two groups (p = 0.54). IN CONCLUSIONS: Obese men with NASH and simple steatosis have similar splanchnic uptake and release of FFA and VLDL-TG and a similar proportion of FFA from VAT lipolysis delivered to the liver. These results suggest that FFA and VLDL-TG splanchnic balances are unaffected by NAFLD severity.

Neonatal Gut and Immune Responses to ß-Casein Enriched Formula in Piglets.

BACKGROUND: ß-casein is the main casein constituent in human milk (HM) and a source of bioactive peptides for the developing gastrointestinal tract and immune system. Infant formulas contain less ß-casein than HM, but whether different concentrations of ß-casein affect tolerability and gut and immune maturation in newborns is unknown. OBJECTIVES: Using near-term piglets as a model for newborn infants, we investigated whether increasing the ß-casein fraction in bovine-based formula is clinically safe and may improve gut and immune maturation. METHODS: Three groups of near-term pigs (96% gestation) were fed formula with bovine casein and whey protein (ratio 40:60): 1) standard skim milk casein (BCN-standard, 35% ß-casein of total casein, n = 18); 2) ß-casein enrichment to HM concentrations (BCN-medium, 65%, n = 19); and 3) high ß-casein enrichment (BCN-high, 91%, n = 19). A reference group was fed 100% whey protein concentrate (WPC) as protein (WPC, n = 18). Intestinal and immune parameters were assessed before and after euthanasia on day 5. RESULTS: Clinical variables (mortality, activity, body growth, and diarrhea) were similar among the groups, and no differences in intestinal or biochemical parameters were observed between BCN-standard and BCN-medium pigs. However, pigs receiving high amounts of ß-casein (BCN-high) had lower small intestine weight and tended to have more intestinal complications (highest gut pathology score, permeability, and interleukin-8) than the other groups, particularly those receiving no casein (WPC pigs). Blood lymphocyte, thrombocyte, and reticulocyte counts were increased with higher ß-casein, whereas eosinophil counts were reduced. In vitro blood immune cell responses were similar among groups. CONCLUSIONS: ß-casein enrichment of bovine-based formula to HM concentrations is clinically safe, as judged from newborn, near-term pigs, whereas no additional benefits to gut maturation were observed. However, excessive ß-casein supplementation, beyond concentrations in HM, may potentially induce gut inflammation together with increased blood cell populations relative to natural ß-casein concentrations or pure whey-based formula.

Using registry data to identify individual dairy cows with abnormal patterns in routinely recorded somatic cell counts.

Data from the Danish milk recording system routinely enter the Danish Cattle Database, including somatic cell counts (SCC) for individual animals. Elevated SCC can signal intramammary inflammation, suggesting subclinical mastitis. Detecting mastitis is pivotal to limit severity, prevent pathogen spread, and target treatment or culling. This study aimed to differentiate normal and abnormal SCC patterns using recorded registry data. We used registry data from 2010 to 2020 for dairy cows in herds with 11 annual milk recordings. To create consistency across herds, we used data from 13,996 unique animals and eight different herds, selected based on the amount of data available, only selecting Holstein animals and conventional herds. We fitted log10-transformed SCC to days in milk (DIM) using the Wilmink and Wood's curve functions, originally developed for milk yield over the lactation. We used Nonlinear Least Square and Nonlinear Mixed Effect models to fit the log10-transformed SCC observations to DIM at animal level. Using mean squared residuals (MSR), we found a consistently better fit using a Wood's style function. Detection of MSR outliers in the model fitting process was used to identify animals with log10(SCC) curves deviating from the expected "normal" curve for that same animal. With this study, we propose a method to identify single animals with SCC patterns that indicate abnormalities, such as mastitis, based on registry data. This method could potentially lead to a registry data-based detection of mastitis cases in larger dairy herds.

Effects of physical form of ß-lactoglobulin and calcium ingestion on GLP-1 secretion, gastric emptying and energy intake in humans: a randomised crossover trial.

The aim of this study was to assess whether adding Ca2+ to aggregate or native forms of ß-lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of ß-lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca2+-rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13C-acetate and 13C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1TOTAL) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v. 1550 ± 456 pmol·l-1·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v. 1844 ± 550 pmol·l-1·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life (P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v. 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v. AGGREG (P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902).

Educational attainment in eating disorders: What can we learn from visualising data.

BACKGROUND: Educational attainment is an understudied outcome in eating disorders (ED). We compared the educational attainment of individuals with and without ED. METHODS: This study is a nationwide, register-based, observational epidemiological study using record linkage. The studied cohorts were (1) all persons treated psychiatrically for ED from 1970 to 2014, and (2) a control population matched for sex, age, and place of residence. The International Standard Classification of Education 2011 was used to classify educational attainment. We employed ineqord, a series of graphical and analytical tools that are appropriate for comparing the distributions of ordinal data (Jenkins, 2020). RESULTS: Females with ED attained higher educational levels than males with ED. Males with ED had lower average educational levels than controls. On average, female controls attained higher educational levels than patients with ED in the eating disorders not otherwise specified or overeating groups. Females with anorexia nervosa, differed from matched controls: While their median was the same, too many participants were in the lower and higher levels of educational attainment. Females with bulimia nervosa had higher educational levels than matched controls on average. CONCLUSIONS: Educational attainment differs between individuals with and without out ED for all ED diagnoses and in both sexes.

Discovery of NSD2-Degraders from Novel and Selective DEL Hits.

NSD2 is a histone methyltransferase predominantly catalyzing di-methylation of histone H3 on lysine K36. Increased NSD2 activity due to mutations or fusion-events affecting the gene encoding NSD2 is considered an oncogenic event and a driver in various cancers, including multiple myelomas carrying t(4;14) chromosomal translocations and acute lymphoblastic leukemia's expressing the hyperactive NSD2 mutant E1099 K. Using DNA-encoded libraries, we have identified small molecule ligands that selectively and potently bind to the PWWP1 domain of NSD2, inhibit NSD2 binding to H3K36me2-bearing nucleosomes, but do not inhibit the methyltransferase activity. The ligands were subsequently converted to selective VHL1-recruiting NSD2 degraders and by using one of the most efficacious degraders in cell lines, we show that it leads to NSD2 degradation, decrease in K3 K36me2 levels and inhibition of cell proliferation.

Bioactive milk peptides: an updated comprehensive overview and database.

Partial digestion of milk proteins leads to the formation of numerous bioactive peptides. Previously, our research team thoroughly examined the decades of existing literature on milk bioactive peptides across species to construct the milk bioactive peptide database (MBPDB). Herein, we provide a comprehensive update to the data within the MBPDB and a review of the current state of research for each functional category from in vitro to animal and clinical studies, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, antioxidant, dipeptidyl peptidase (DPP)-IV inhibitory, opioid, anti-inflammatory, immunomodulatory, calcium absorption and bone health and anticancer activity. This information will help drive future research on the bioactivities of milk peptides.

Clinical outcomes using a 3D printed tandem-needle-template and the EMBRACE-II planning aims for image guided adaptive brachytherapy in locally advanced cervical cancer.

BACKGROUND: Extensive local disease or narrow vagina may compromise brachytherapy (BT) in patients with cervical cancer. This is the first study to analyze long-term outcomes of using 3D printed vaginal tandem-needle templates (3DP TNT) for transvaginal insertion of needles in parallel (P) or parallel and oblique (P&O) direction to the tandem. MATERIAL AND METHODS: All patients treated with BT using 3DP TNT from 2015-2020 were included. Decision to use a 3DP TNT and preplanning were made after 4-5 weeks of external beam radiotherapy, based on gynecological examination and MRI with a tandem-ring applicator in situ. The TNT was 3D-printed in house consisting of a circular template with P&O holes for guidance of plastic needles and a shaft fitting the uterine tandem. Thus, the radioactive source was never in direct contact with the 3DP TNT. The TNT was 3D printed in a standard or personalized configuration. Planning aims were based on the Embrace II protocol. RESULTS: 101 patients (median age of 63 years) were included: 49 with P needles only and 52 with P&O needles. Personalized TNT was used in 19 patients in the P&O group. Performance status (WHO) was > 0 in 48%. FIGO2018 stage III-IV was present in 77%. T-score at diagnosis and BT was 9.1 and 6.3 respectively, with a significantly higher T-score in the P&O compared to P group. The mean high-risk CTV D90 was 93 Gy with no significant difference between the two groups. Three-year local control rates were 85%, 95%, 75% for the overall, P- and P&O group respectively and 68%, 80% and 56% for cancer specific survival. Grade ≥3 treatment related complications were observed in 10 (10%) patients. CONCLUSIONS: 3DP TNT for BT in cervical cancer provides successful management of very extensive local disease and/or unfavorable anatomy with the possibility for treatment individualization.

Overview and Challenges of Large-Scale Cultivation of Photosynthetic Microalgae and Cyanobacteria.

Microalgae and cyanobacteria are diverse groups of organisms with great potential to benefit societies across the world. These organisms are currently used in food, feed, pharmaceutical and cosmetic industries. In addition, a variety of novel compounds are being isolated. Commercial production of photosynthetic microalgae and cyanobacteria requires cultivation on a large scale with high throughput. However, scaling up production from lab-based systems to large-scale systems is a complex and potentially costly endeavor. In this review, we summarise all aspects of large-scale cultivation, including aims of cultivation, species selection, types of cultivation (ponds, photobioreactors, and biofilms), water and nutrient sources, temperature, light and mixing, monitoring, contamination, harvesting strategies, and potential environmental risks. Importantly, we also present practical recommendations and discuss challenges of profitable large-scale systems associated with economical design, effective operation and maintenance, automation, and shortage of experienced phycologists.

Perceptions of the rabbit as a low investment 'starter pet' lead to negative impacts on its welfare: Results of two Danish surveys.

Concerns over compromised companion rabbit (Oryctolagus cuniculus domesticus) welfare are widespread. The welfare problems have been linked to the perception of rabbits as low investment 'children's pets.' To test this hypothesis and investigate the current conditions for rabbits, data were gathered from two surveys in 2021: a nationally representative survey of Danish companion animal owners (Survey I) and a detailed social media-based survey of Danish rabbit owners (Survey II). Using logistic regression, three owner-related variables (whether a child/adult was responsible for care of the rabbit, owner-opinion on rabbits' suitability as 'starter pets' and willingness-to-pay [WTP] for veterinary treatment) were employed to investigate the effect of rabbit status on owner-provision of selected husbandry conditions. The 76 (Survey I) and 4,335 (Survey II) responses suggested that most rabbits are acquired for children and are solitarily housed, and that many are kept in cages of an unsuitable size and not checked daily. Owners who perceived rabbits as 'starter pets' and with lower WTP were more likely to house rabbits in restricted space and to not provide continuous gnawing opportunities, ad libitum hay or routine healthcare. A child fulfilling the role of the rabbit's main caretaker was also associated with inadequate housing type and fewer gnawing opportunities. Thus, many rabbits live in unsuitable conditions, and owners who perceive rabbits as low investment 'children's pets' are more likely to not provide recommended resources. Changing owners' perceptions of rabbits and promoting suitable husbandry through official education programmes and minimum requirements is important if there are to be improvements made to rabbit welfare.

The Entropy of Entropy: Are We Talking about the Same Thing?

In the last few decades, the number of published papers that include search terms such as thermodynamics, entropy, ecology, and ecosystems has grown rapidly. Recently, background research carried out during the development of a paper on "thermodynamics in ecology" revealed huge variation in the understanding of the meaning and the use of some of the central terms in this field-in particular, entropy. This variation seems to be based primarily on the differing educational and scientific backgrounds of the researchers responsible for contributions to this field. Secondly, some ecological subdisciplines also seem to be better suited and applicable to certain interpretations of the concept than others. The most well-known seems to be the use of the Boltzmann-Gibbs equation in the guise of the Shannon-Weaver/Wiener index when applied to the estimation of biodiversity in ecology. Thirdly, this tendency also revealed that the use of entropy-like functions could be diverted into an area of statistical and distributional analyses as opposed to real thermodynamic approaches, which explicitly aim to describe and account for the energy fluxes and dissipations in the systems. Fourthly, these different ways of usage contribute to an increased confusion in discussions about efficiency and possible telos in nature, whether at the developmental level of the organism, a population, or an entire ecosystem. All the papers, in general, suffer from a lack of clear definitions of the thermodynamic functions used, and we, therefore, recommend that future publications in this area endeavor to achieve a more precise use of language. Only by increasing such efforts it is possible to understand and resolve some of the significant and possibly misleading discussions in this area.

Localization of aquaglyceroporins in human and murine white adipose tissue.

The glycerol channel AQP7 facilitates glycerol efflux from adipose tissue (AT), and AQP7 deficiency has been suggested to promote obesity. However, the release of glycerol from AT is not fully blocked in AQP7-deficient mice, which suggests that either alternative glycerol channels are present in AT or significant simple diffusion of glycerol occurs. Previous investigations of the expression of other aquaglyceroporins (AQP3, AQP9, AQP10) than AQP7 in AT are contradictory. Therefore, we here aim at determining the cellular localization of AQP3 and AQP9 in addition to AQP7 in human and mouse AT using well-characterized antibodies for immunohistochemistry (IHC) and immunoblotting as well as available single-cell transcriptomic data from human and mouse AT. We confirm that AQP7 is expressed in endothelial cells and adipocytes in human AT and find ex vivo evidence for interaction between AQP7 and perilipin-1 in adipocytes. In addition, labeling for AQP7 in human AT also includes CD68-positive cells. No labeling for AQP3 or AQP9 was identified in endothelial cells or adipocytes in human or mouse AT using IHC. Instead, in human AT, AQP3 was predominantly found in erythrocytes, whereas AQP9 expression was observed in a small number of CD15-positive cells. The transcriptomic data revealed that AQP3 mRNA was found in a low number of cells in most of the identified cell clusters, whereas AQP9 mRNA was found in myeloid cell clusters as well as in clusters likely representing mesothelial progenitor cells. No AQP10 mRNA was identified in human AT. In conclusion, the presented results do not suggest a functional overlap between AQP3/AQP9/AQP10 and AQP7 in human or mouse white AT.

Macronutrient niches and field limitation in a woodland assemblage of harvestmen.

Description of animals' trophic niches helps us understand interactions between species in biological communities that are not easily observed. Analyses of macronutrient niches, that is, the range of macronutrient (protein:lipid:carbohydrate) ratios selected by generalist feeders, may be a useful alternative approach to inter-species comparisons of diets, especially within taxonomic assemblages of predators where species with similar nutritional requirements are likely to accept similar types of prey. Here we analysed the macronutritional niches of a woodland assemblage of seven harvestman species, all supposed to be predators with omnivorous tendencies. Five species (Mitopus morio, Leiobunum gracile, Oligolophus tridens, O. hanseni and Paroligolophus agrestis) were native and two species (Opilio canestrinii and Dicranopalpus ramosus) were recent invaders into the community. We compare the fundamental (FMN) and realized (RMN) macronutritional niche positions of the species using a 'double-test procedure', which provides information on whether the species were food limited in their natural habitat, and whether they were limited by specific macronutrients. All seven species were food limited and six species were non-protein limited in the field; of these, four species were carbohydrate limited, and in one species females were lipid limited and males were carbohydrate limited. These findings add to the notion that predators are mainly non-protein limited in the field. The FMN positions of the assemblage fell within 46%-50% protein, 29%-38% lipid and 16%-22% carbohydrate. The amount of carbohydrate in the self-selected diet combined with carbohydrate limitation confirms that the species are zoophytophagous. Two morphological clusters of species (large long-legged vs. small short-legged species) differed not only in microhabitat (upper vs. lower forest strata) but also in macronutrient selection, where large long-legged species selected higher proportion of carbohydrate than small short-legged species. Thus, morphologically similar species occupy the same habitat stratum and have similar macronutritional niches. We discuss the hypothesis that the invasive O. canestrinii might have an impact on native species as it allegedly had in urban environments previously. Two basic assumptions about interspecific resource competition were fulfilled, that is, high overlap of nutritional requirements and limitation by food and macronutrients.

Diverse repertoire of human adipocyte subtypes develops from transcriptionally distinct mesenchymal progenitor cells.

Single-cell sequencing technologies have revealed an unexpectedly broad repertoire of cells required to mediate complex functions in multicellular organisms. Despite the multiple roles of adipose tissue in maintaining systemic metabolic homeostasis, adipocytes are thought to be largely homogenous with only 2 major subtypes recognized in humans so far. Here we report the existence and characteristics of 4 distinct human adipocyte subtypes, and of their respective mesenchymal progenitors. The phenotypes of these distinct adipocyte subtypes are differentially associated with key adipose tissue functions, including thermogenesis, lipid storage, and adipokine secretion. The transcriptomic signature of "brite/beige" thermogenic adipocytes reveals mechanisms for iron accumulation and protection from oxidative stress, necessary for mitochondrial biogenesis and respiration upon activation. Importantly, this signature is enriched in human supraclavicular adipose tissue, confirming that these cells comprise thermogenic depots in vivo, and explain previous findings of a rate-limiting role of iron in adipose tissue browning. The mesenchymal progenitors that give rise to beige/brite adipocytes express a unique set of cytokines and transcriptional regulators involved in immune cell modulation of adipose tissue browning. Unexpectedly, we also find adipocyte subtypes specialized for high-level expression of the adipokines adiponectin or leptin, associated with distinct transcription factors previously implicated in adipocyte differentiation. The finding of a broad adipocyte repertoire derived from a distinct set of mesenchymal progenitors, and of the transcriptional regulators that can control their development, provides a framework for understanding human adipose tissue function and role in metabolic disease.

Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein.

Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. It was shown that after purification, the κ-CN molecules reassembled into multimer states, which then constituted the basis for the digestion studies. As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. This finding could be applied to produce dairy products with enhanced digestibility.

Increase in infected corneal ulcerations in dogs during the northern Colorado's 2020 wildfire season.

OBJECTIVE: In the fall of 2020, Colorado experienced the two largest wildfires in state history. The smoke blanketed the college town of Fort Collins, Colorado, the location of the Veterinary Teaching Hospital at Colorado State University (CSU-VTH). The objective for this cross-sectional observational study was to evaluate how these wildfires and the corresponding elevated air quality index (AQI)) was associated with infected corneal ulcerations in dogs when compared to the two previous years. ANIMALS: Seventeen dogs were included in this study. PROCEDURES: Medical records from dogs presented to the CSU-VTH ophthalmology service with infected corneal ulcerations in August, September, and October of 2020, 2019, and 2018 were evaluated. Only corneal ulcerations with growth on their microbial cultures were included in this study. RESULTS: The study revealed a significant increase in prevalence of infected corneal ulcerations in dogs presented to the CSU-VTH during the three wildfire months of 2020 that is, 3.5% (9/255) when compared with the two previous years, 2019: 1.0% (4/383, p = 0.04), and 2018: 0.9% (4/457) (p = .01). The AQI (mean ± standard error) was also significantly elevated for dogs that presented with infected corneal ulcerations in 2020 (70.2 ± 5.8) compared with 2019 (19.7 ± 8.7) and 2018 (45.6 ± 8.7) (p < .01). CONCLUSIONS AND CLINICAL RELEVANCE: Elevation of AQI from wildfires seems to be correlated with an increased prevalence of infected corneal ulceration in dogs. As the duration and frequency of wildfires continues to rise globally, the effects of these wildfires on animal health should be investigated further.

Issues with the European Pharmacopoeia Quality Control Method for 99mTc-Labelled Macroaggregated Albumin.

Technetium-99m macroaggregated albumin ([99mTc]Tc-MAA) is an injectable radiopharmaceutical used in nuclear medicine for lung perfusion scintigraphy. After changing to a new batch of macroaggregated albumin (MAA), we saw unwanted uptake in the liver and spleen. The batch was therefore tested by both the supplier and us and we found it to comply with the requirements of the European Pharmacopoeia (Ph. Eur.). However, a simple comparison between the problematic batch and a batch supplied by another manufacturer showed that there was a significant difference. The quality testing showed a higher number of small particles in the problem encumbered MAA batch with unwanted in vivo uptake. In this article we present a simple method of testing for particle size of [99mTc]Tc-MAA, which gives a good indication of how the radioactive drug performs in vivo. We argue that the quality control method described in the Ph. Eur. should be changed. The changes will improve concordance between the laboratory analyzes and what is seen in vivo in human lung perfusion scintigraphy. Furthermore, we hope that the MAA suppliers without delay will replace their release procedure to be in accordance with the method described in this article.

Differential in vitro digestion rates in gastric phase of bovine milk with different κ-casein phenotypes.

Casein (CN) micelles will coagulate in the stomach after ingestion, which is similar to the cheesemaking process. Although genetic variants of bovine proteins, especially κ-CN, have been confirmed to influence the coagulation properties of the CN micelle, its influence on milk digestibility has not been revealed yet. This study aimed to investigate how genetic variants, glycosylation degree of κ-CN, and CN micelle size influence digestion rates during in vitro gastrointestinal digestion. Three milk pools, representing κ-CN phenotypes of either AA, BB, or AB composition were prepared from milk of individual Danish Holstein cows representing these different genotypes. In vitro digestion of the 3 milk pools, AA, BB, or AB, was investigated by sodium dodecyl sulfate-PAGE, liquid chromatography-mass spectrometry, and degree of hydrolysis. The results showed that κ-CN AA milk had faster digestion rate in the gastric phase compared with BB and AB milks, whereas only small differences were apparent in the intestinal digestion phase. The results further documented that the milk pools representing κ-CN phenotypes BB and AB had comparable overall glycosylation degrees (50.9% and 50.0%, respectively) and higher than that of the AA milk pool (46.9%). Further, the AA milk pool was associated with larger CN micelles. These differences in CN micelle sizes and glycosylation degrees can be part of underlying explanations for the differential in vitro digestion rates observed between the AA, BB, and AB κ-CN milk pools.