Blood Chemistry Research Articles

A Report on Attempts to Acquire Exercise Habits Through Japanese Health Education for Adult Workers from Cebu, Philippines

Background: Good health is a pivotal aspect of daily life that contributes to social development. Physical activity is a vital component of a healthy lifestyle. Health promotion enables individuals to increase their control and improve their health, and health programs promote physical activity to improve health. Objectives: This study aims to introduce the Japanese health education guidelines according to the requirements of the International Organization for Standardization (ISO) 9001-certified health education system in the Cebu region of the Philippines and aims to improve the health of the participants. Methods: A 12-month health program was implemented in Cebu City, and 43 participants were recruited, aged 35.0 ± 9.9 years (mean ± SD), including 22 men aged 35.6 ± 7.9 years and 21 women aged 34.3 ± 7.9 years. The effects of the health program and physical activity were assessed using brain function tests and blood chemistry profiles before and after the program. Results: The average number of total daily steps taken by the 43 participants was 6,052. The weight and eyes-open single-leg stance for balance significantly improved. However, no significant differences were observed in the other physical fitness parameters, blood pressure, and brain function values. Conclusions: This health education is characterized by a mechanism that enables the setting of the next goal based on these evaluations and how to improve health. The participants have to be motivated to aim for a 7,000 daily step goal. Therefore, the participants and the staff involved in health education should build a relationship of trust and a deep bond, and the exercise continuation rate may increase, leading to a higher quality of life.

Intramuscular administration of tranexamic acid in a large swine model of hemorrhage with hyperfibrinolysis.

Traumatic injury with subsequent hemorrhage is one of the leading causes of mortality among military personnel and civilians alike. Posttraumatic hemorrhage accounts for 40% to 50% of deaths in severe trauma patients occurring secondary to direct vessel injury or the development of trauma-induced coagulopathy (TIC). Hyperfibrinolysis plays a major role in TIC and its presence increases a patient's risk of mortality. Early therapeutic intervention with intravenous (IV) tranexamic acid (TXA) prevents development of hyperfibrinolysis and subsequent TIC leading to decreased mortality. However, obtaining IV access in an austere environment can be challenging. In this study, we evaluated the efficacy of intramuscular (IM) versus IV TXA at preventing hyperfibrinolysis in a hemorrhaged swine. Yorkshire cross swine were randomized on the day of study to receive IM or IV TXA or no treatment. Swine were sedated, intubated, and determined to be hemodynamically stable before experimentation. Controlled hemorrhaged was induced by the removal of 30% total blood volume. After hemorrhage, swine were treated with 1,000 mg of IM or IV TXA. Control animals received no treatment. Thirty minutes post-TXA treatment, fibrinolysis was induced with a 50-mg bolus of tissue plasminogen activator. Blood samples were collected to evaluate blood TXA concentrations, blood gases, blood chemistry, and fibrinolysis. Blood TXA concentrations were significantly different between administration routes at the early time points but were equivalent by 20 minutes after injection, remaining consistently elevated for up to 3 hours postadministration. Induction of fibrinolysis resulted in 87.18 ± 4.63% lysis in control animals, compared with swine treated with IM TXA, 1.96 ± 2.66% and 1.5 ± 0.42% lysis in the IV TXA group. In the large swine model of hemorrhage with hyperfibrinolysis, IM TXA is bioequivalent and equally efficacious in preventing hyperfibrinolysis as IV TXA administration.

Circadian regulation of calcium and phosphorus homeostasis during the oviposition cycle in laying hens

Maintenance of calcium and phosphorus homeostasis in laying hens is crucial for preservation of skeletal integrity and eggshell quality, though physiological regulation of these systems is incompletely defined. To investigate changes in mineral and vitamin D3 homeostasis during the 24-h egg formation cycle, 32-wk-old commercial laying hens were sampled at 1, 3, 4, 6, 7, 8, 12, 15, 18, 21, 23, and 24 h post-oviposition (HPOP; n ≥ 4). Ovum location and egg calcification stage were recorded, and blood chemistry, plasma vitamin D3 metabolites, circulating parathyroid hormone (PTH), and expression of genes mediating uptake and utilization of calcium and phosphorus were evaluated. Elevated levels of renal 25-hydroxylase from 12 to 23 HPOP suggest this tissue might play a role in vitamin D3 25-hydroxylation during eggshell calcification. In shell gland, retinoid-x-receptor gamma upregulation between 6 and 8 HPOP followed by subsequently increased vitamin D receptor indicate that vitamin D3 signaling is important for eggshell calcification. Increased expression of PTH, calcitonin, and fibroblast growth factor 23 (FGF23) receptors in the shell gland between 18 and 24 HPOP suggest elevated sensitivity to these hormones toward the end of eggshell calcification. Shell gland sodium-calcium exchanger 1 was upregulated between 4 and 7 HPOP and plasma membrane calcium ATPase 1 increased throughout eggshell calcification, suggesting the primary calcium transporter may differ according to eggshell calcification stage. Expression in shell gland further indicated that bicarbonate synthesis precedes transport, where genes peaked at 6 to 7 and 12 to 18 HPOP, respectively. Inorganic phosphorus transporter 1 (PiT-1) expression peaked in kidney between 12 and 15 HPOP, likely to excrete excess circulating phosphorus, and in shell gland between 18 and 21 HPOP. Upregulation of FGF23 receptors and PiT-1 during late eggshell calcification suggest shell gland phosphorus uptake is important at this time. Together, these findings identified potentially novel hormonal pathways involved in calcium and phosphorus homeostasis along with associated circadian patterns in gene expression that can be used to devise strategies aimed at improving eggshell and skeletal strength in laying hens.

Use of inclisiran in a real-world setting: results from the italian Cholinet registry

Abstract Background Real world data indicate that PCSK9 inhibitors (PCSK9i) are started in very high-risk patients at higher LDL cholesterol (LDL-C) values than those recommended by guidelines. Different reimbursement rules may have an impact on access to injectable therapy among different countries. In Italy, reimbursement of injectable lipid lowering therapies (LLT) (i.e., PCSK9i and inclisiran) has been recently allowed for very high risk patients with LDL-C levels >70 mg/dl while on statin/ezetimibe LLT or statin intolerant, and, thereafter, inclisiran has been introduced in clinical practice. No data are available on inclisiran real world use in Italy and on the impact of new reimbursement rules on patient access to inclisiran. Purpose Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry involving 21 Italian centers, designed to assess efficacy, safety, adherence and persistence, as well characteristics of very high risk patients with atherosclerotic CV disease (ASCVD) and/or familial hypercholesterolemia (FH) receiving inclisiran. Methods From November 2022 through February 2023, the Cholinet registry enrolled patients receiving inclisiran due to elevated LDL-C levels in Italian centers as part of their medical therapy. Baseline characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at follow-up. Results We enrolled 105 patients (14% FH, 30% female, mean age 64 years) receiving inclisiran according to standard clinical practice. 37 of them reached 3 months follow up (i.e., time of first reinjection dose) and none of them missed the reinjection dose. At the time of inclisiran first prescription median LDL-C was 96.6 mg/dl and reached 48.8 mg/dl at the time of 3 months observation (49% reduction). In patients with ASCVD median LDL-C at baseline was 90.4 mg/dL and 44.4 mg/dl at follow-up (51% reduction). In patients with FH median LDL-C at baseline was 177.4 mg/dL and 109.5 mg/dL at follow-up (38% reduction). Of 105 patients enrolled, 92 patients (88%) were on LLT. Heterogeneity was found on the LDL-C reduction across our cohort (Figure 1) (Shapiro-Wilk test p<0.05) that appeared to be influenced by background LLT (Kruskal-Wallis rank for previous PCSK9i exposure p=0.0028, for background LLT p=0.0435) (Figure 2), but not by baseline LDL-C levels (ANOVA p=0.06). LDL-C target was achieved in 21 (66%) of 32 patients receiving background LLT and in 2 (40%) of 5 patients who did not. No patient reported side effects. Conclusion These preliminary results from the Cholinet registry show that, in a context of facilitated reimbursement access, inclisiran is introduced at substantially lower baseline LDL-C values than previously reported for PCSK9i, reflecting a favorable change in clinical practice. Inclisiran effectively and safely reduces LDL-C in patients with ASCVD or FH, with some etherogeneity that was associated with background LLT.Kernel density plot, LDL-C % reductionStratified Kernel density plot

Efficacy and safety of inclisiran in real world practice: insights from the Cholinet registry

Abstract Background Inclisiran has been recently introduced in clinical practice. Thus, efficacy and safety data from real world settings are scarce. In Italy, reimbursement of inclisiran has been recently introduced for very high cardiovascular (CV) risk patients with LDL cholesterol (LDL-C) >70 mg/dl on statin/ezetimibe background lipid lowering therapy (LLT). Purpose Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry involving 21 Italian centers, designed to assess efficacy, safety, adherence and persistence of inclisiran, and clinician’s behavior on LLT in very high CV risk patients with atherosclerotic CV disease and/or familial hypercholesterolemia (FH). Methods From November 2022 through February 2023, the Cholinet registry enrolled patients receiving inclisiran in Italian centers as part of their optimal medical therapy. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and in subsequent follow-up. Background therapy was assessed to evaluate treatment withdrawal, reduction of doses or any change from baseline during follow up. Results We enrolled 105 patients (14% with FH, 30% female, mean age 64 years) receiving inclisiran according to standard clinical practice. Data on follow-up at 3 months (i.e., time of first reinjection dose) were available for 37 of them. At the time of inclisiran first prescription median LDL-C was 96.6 mg/dl and reached 48.8 mg/dl at the time of 3 months observation (49% mean reduction, 47,8 mg/dl absolute median reduction). None of the 37 patients reaching 3 months follow up missed the reinjection dose administration. Of 105 patients enrolled, 92 patients (88%) were on LLT, of them 16 (17%) were on ezetimibe alone, 11 (12%) on statin alone and 65 (71%) on a statin and ezetimibe combination. Of the enrolled patients, 6 (6%) were previously treated with evolocumab and 4 (4%) with alirocumab. At the end of the observation period, of the 37 patients with a follow-up, 18 (49%) did not change background LLT. Of 19 patients changing background LLT, 3 withdrew therapy (16%) and 16 (84%) reduced dose or changed type of LLT. Among patients evaluated at 3 months follow up, 23 patients (62%) achieved their target LDL-C (Figure 1), of them 21 (91%) were on LLT (Figure 2). No adverse drug reactions were reported. Conclusion These preliminary findings from the Cholinet Italian registry show that inclisiran effectively reduces (49%) LDL-C in real world settings, with no patients missing the first reinjection dose. Yet, concomitant LLT was reduced or discontinued in 51% of patients. Target LDL-C was achieved in 23 out of 37 patients, 21 of them receiving LLT background therapy. Thus, combination of oral therapy and inclisiran is needed in the majority of very high CV risk patients to achieve LDL target, and use of inclisiran should not prompt discontinuation or reduction of concomitant LLT.LLT in patient achieving LDL-C targetLDL-C target % by LLT

Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: a single country, multicenter, observational study (AT-TARGET-IT)

Abstract Background PCSK9 inhibitors (PCSK9i) significantly decrease LDL cholesterol (LDL-C), either as monotherapy or in addition to the maximally tolerated dose of statin and/or ezetimibe. Yet, few data are available on efficacy and background lipid-lowering therapy (LLT) adjustment in patients treated with PCSK9i in real-world observations. Purpose AT-TARGET-IT is an Italian multicenter registry involving 9 Italian centers, designed to assess efficacy, adherence, and persistence of PCSK9i, as well as prescribing doctors’ behavior in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). Methods From June through November 2021, we enrolled patients with PCSK9i first prescription from 6 months before inclusion through starting of PCSK9i use. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at the latest observation preceding inclusion in the study. Background therapy was assessed at baseline and during follow-up, evaluating treatment withdrawal, reduction of doses, or changes from statin-ezetimibe association to single drug therapy. Results 798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not (Figure 1). 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence (Figure 2). At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. Conclusion PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.Stratified LDL-C target achievementAdherence and persistence status

Double-Masked, Vehicle-Controlled, Randomized, Phase II Study of the Ocular Hypotensive Activity and Safety of VVN539 Ophthalmic Solution

To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study. Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study. Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices. After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days). Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21). Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures. In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract 14730: The Effect of Electronic Cigarette Exposure With Nicotine on Expression of Inflammatory Genes and Blood Parameters in a Chronic Myocardial Infarction Model

Background: There are no data available regarding the effects of chronic electronic cigarette (eC) exposure on inflammatory gene expressions after myocardial infarction (MI) and whether eC could alter blood counts and chemistries in this setting. We determined the effect of eC on expression of genes for inflammatory cytokines and receptors and blood parameters during the healing phase of MI. Methods and Results: Sprague Dawley rats of either sex were subjected to a proximal left coronary artery occlusion to induce a large anterior wall MI. At 1 week, rats were randomized to exposure to air or E-cig with nicotine (eC Nic + ) for 12 weeks. After 12 weeks of exposure, rat inflammatory cytokine and receptor PCR array was performed (n=4 in each group). The data showed 70 out of 84 inflammatory-related genes were downregulated in the eC Nic+ group versus the air group and 11 downregulated genes reached a significant difference. Interleukin 6 (IL6), Tumor necrosis factor superfamily (TNF), Chemokine (C-C motif) ligand 12 (Ccl12), and C-X-C Motif Chemokine Receptor 3 (Cxcr3) gene expressions were significantly decreased by -6.49 fold, p=0.0048, -2.63 fold, p=0.0227, -2.71 fold, p=0.0146, and -2.28 fold, p=0.0067, respectively, in the eC Nic+ group vs air group. The rats in eC Nic+ group had significantly decreased white blood cell (WBC), lymphocyte and platelet count compared to the air group (Figure). Conclusions: Exposure to eC Nic+ alters the expression of inflammatory genes and decreases blood immune cells during the healing phase of MI. Our findings suggest that chronic inhalation of e-cigarette aerosols can suppress the immune and inflammatory response in the already compromised setting of MI.

Abstract 18755: Engineered Nanoparticles for the Oral Delivery of Cardioprotective Small RNA Therapeutics

Background: RNA drugs have been applied to cardiovascular conditions including hypercholesterolemia and amyloidosis, but such drugs are deliverable only by parenteral routes. The ability to deliver RNA drugs orally would be highly desirable. Here we describe the development of a casein-chitosan-based formulation (dubbed C2) for the oral delivery of TY1, a 24-nucleotide chemically-modified Y RNA which we are exploring as a therapeutic candidate for cardiac fibrosis. Materials and Methods: We characterized the size distribution of C2-encapsulated TY1 (C2-TY1) micelles by nanoparticle tracking analysis. qPCR quantified the number of TY1 copies per micelle, as well as the presence of exogenous RNA in intestinal tissue from animals fed C2-conjugated RNA. Using a mucin precipitation assay, we assessed the ability of C2 micelles to adsorb onto mucin. We then tested the resistance of C2-TY1 micelles to degradation through incubation with proteinase K and RNase. To assess safety, healthy animals were fed C2-TY1 (0.15mg/kg, comparable to doses effective intravenously), or vehicle (H 2 O), twice weekly and evaluated at four weeks. Finally, we gauged the therapeutic potential of orally-administered C2-TY1 in a rat model of myocardial infarction. Results: C2 micelles are 100-500 nm in size and efficiently encapsulate TY1 (~10 4 TY1 copies per particle; n=3 technical replicates). After oral gavage, C2 efficiently delivered exogenous RNA to intestinal tissue within 60 minutes, as verified by qPCR (n=9). Chitosan played a significant role in the mucoadhesive property of C2 (n=6). C2 protected TY1 from enzymatic degradation compared with other formulations (p<0.01; n=3 per group). In vivo , animals fed C2-TY1 had stable weight, exercise endurance, CBC and blood chemistry relative to controls, with no histologic abnormalities in vital organs (n=3-5 per group). When administered orally 20 minutes after reperfusion, C2-TY1 reduced infarct size (p<0.01) and decreased circulating levels of troponin I (p<0.05; n=3-6 per group). Preliminary findings show similar oral efficacy of two other, chemically-unrelated, small RNA drugs encapsulated in C2. Conclusion: The C2 formulation enables efficient and effective oral delivery of small RNA drugs for cardioprotection.

PSX-30 Scratching the Surface: Investigating the Nature and Potential Causes of Pruritic Cattle

Abstract Depending on the year, during the winter months, cattle begin to rub bare patches on their skin due to pruritus which leads to concern from cattle producers, especially the purebred breeders. Upon further investigation by veterinarians, the cause is not always caused by lice, as many may think. This study aimed to provide insight into the cause and potential prevention/treatment of pruritic beef cattle in western Canada by examining herds that met the study’s criteria of having more than 30% of the herd exhibiting pruritus. Seven herds were examined in the winter of 2023: one from Manitoba, two from Saskatchewan, and four from Alberta. Producers from each herd completed a detailed survey on treatments, nutrition, and environmental conditions and provided feed, water, and bedding samples. Within each herd, five cattle considered non-pruritic, and ten cattle considered pruritic by visual appraisal were enrolled for standard data collection consisting of documentation and photos of skin lesions localized to pruritic areas, general health clinical exam, lice exam/collection, mite exam/collection of hairs, skin hydration (corneometer), blood chemistry and vitamin/minerals, and kidney/liver enzymes for mycotoxins. A subset of the group (1 non-pruritic and 4 pruritic) was selected for advanced data collection, including dermal hypersensitivity (grass, alfalfa, grain, weeds, and molds) measured by swelling score and infrared camera temperature measurement compared with positive and negative controls, skin punch biopsies for eosinophils (IgE) and liver biopsies for copper levels. Only 21/101 cattle had lice (18 animals < 10 lice per 6.5 cm2). No significant correlation was observed between cattle with lice and being pruritic (P > 0.05). Dermal hypersensitivity was very low across both pruritic and non-pruritic cattle and was not different (P > 0.05). Skin hydration readings within animals comparing pruritic and non-pruritic areas on their body showed only one herd having significantly (P < 0.05) drier skin on pruritic locations compared with normal locations. Vitamin A, E, and copper blood analysis showed no significant difference between pruritic and non-pruritic cattle. However, liver biopsy copper levels were (P = 0.01) less in pruritic than non-pruritic cattle. Results suggest that the cause of pruritic cattle is not necessarily a result of intense lice infestations but rather multifactorial in nature, and a decision tree for producers and veterinarians should be developed to aid in determining the correct course of action to alleviate pruritic cattle in the field.

PSI-2 Evaluation of Sorghum Pericarp Varieties on Blood Parameters and Antioxidant Capacity in Healthy Adult Dogs

Abstract Ingredients that provide health benefits are popular in the pet food industry. Sorghum contains polyphenols which are found in the pericarp. These polyphenols may provide health benefits due to their antioxidant properties, which increase the benefit of sorghum in pet food. Few pet food studies have evaluated the antioxidant capacity of sorghum differing in pericarp color. The objective of this study was to evaluate the effect of sorghum varieties on blood parameters and antioxidant capacity in dogs. Nutritionally complete experimental diets were extruded with a 50% inclusion of either rice, white sorghum A, burgundy sorghum, or white sorghum B. Twelve dogs were fed dietary treatments in a replicated 4 x 4 Latin square design consisting of 14-day periods. Three milliliters of blood were taken from each dog prior to starting the trial for baseline antioxidant capacity. At the end of each period, 3 mL of blood were taken from each dog and stored at -80°C until further analysis. Blood samples were analyzed for complete blood count (CBC), chemistry profiles (Kansas State University Veterinary Diagnostics Lab, Manhattan, KS), and oxygen radical absorbance capacity (ORAC) was measured by kit in blood plasma. Data were analyzed using a mixed model with statistical analysis software (SAS version 9.4, SAS Institute, Inc., Cary, NC) with treatment and period as fixed effects and dog as a random effect. Red blood cell distribution width was greatest in dogs fed white sorghum A at 12.9% and least in dogs fed white sorghum B at 12.7% (P < 0.05). The anion gap was highest for dogs fed the rice treatment at 24.6 mmol/L and lowest for dogs fed white sorghum A at 22.8 mmol/L (P < 0.05). Cholesterol was greater (P < 0.05) in dogs fed the rice treatment at 246.0 mg/dL compared with the three sorghum varieties (average, 225 mg/dL). Despite the few differences in blood parameters, all were within normal ranges for healthy dogs. There was no difference in plasma ORAC between treatments (P > 0.05). In conclusion, sorghum resulted in normal blood profiles and did not alter plasma antioxidant capacity compared with the rice control when fed to dogs. If antioxidant potential is desired, a concentrated pericarp (bran) extract may be necessary.

PSVIII-20 A Premium Dry Cat Food Enhances Digestibility and Gut Health in Cats Compared with a Grocery Dry Cat Food

Abstract As the awareness of pet owners to the benefits of nutrition on pet health and wellness increases, pet owners are looking for foods that include high-quality ingredients and functional benefits. However, little research is available on cats comparing health measures when feeding premium foods vs basic cat foods. This study aimed to compare the effects of feeding a premium cat kibble diet (Blue Buffalo Tastefuls; BB) and a basic grocery cat kibble diet on digestibility, blood biomarkers, and fecal microbiome in healthy adult cats. Sixty cats (mean BW = 4.2 ± 0.8 kg; mean age = 4.3 ± 3.2 yr) were randomly selected to consume BB (n = 30) or grocery diet (n = 30) for 180 days. On days 0, 90, and 180, fresh fecal samples were collected for fecal microbiome and dysbiosis index analysis and blood samples were collected for measurements of complete blood count, serum chemistry, and serum biomarkers. A separate 10-day digestibility study was conducted using 14 cats (BB n = 7, grocery diet n = 7; mean BW = 3.8 ± 0.7 kg). Total fecal samples were collected from day 6 to day 10 for nutrient digestibility analysis. Protocols were approved by the facility’s Institutional Animal Care and Use Committee before the study. All data were analyzed using the Mixed Models procedure of SAS. Fecal scores were not changed (P > 0.05) by diet. Greater (P < 0.05) digestibility of protein, fat, and energy were observed in cats consuming BB. Although all blood cell count and blood chemistry values were within the reference ranges, measurements such as total protein, aspartate transaminase, alkaline phosphatase, cholesterol, and triglycerides were significantly different (P < 0.05) between diet groups. Greater (P < 0.05) insulin-like growth factor-1 was observed in cats fed BB. Cats consuming BB had a lower (P < 0.05) dysbiosis index (less dysbiotic microbiome) and a greater (P < 0.05) bacterial species richness. Relative abundances of 28 bacterial genera were altered (P < 0.05) by the diets, with greater abundances of Faecalibacterium, Megamonas, and Ruminococcus observed in cats fed BB. The data suggest that a premium dry cat food may elicit beneficial effects on digestibility and the GI microbiome of healthy adult cats.

PSVI-8 Bisphosphonate Pharmacokinetics in Juvenile Horses

Abstract Bisphosphonates alter bone metabolism via inhibition of osteoclastic bone resorption. Although bisphosphonates are beneficial to treat bone disease, extra-label use in healthy juvenile horses may interfere with normal bone metabolism. The objective was to determine plasma pharmacokinetics of the bisphosphonate clodronate disodium (CD) following a single intramuscular dose to better define the time course of CD in juvenile horses. Ten yearling Quarter Horses (334 ± 18 kg, 504 ± 13 d of age) were used to test the hypothesis that juvenile horses would have faster clearance rate of CD compared with previously published data in adult horses. Horses were placed in individual stalls, jugular intravenous catheters were inserted, and an initial blood sample (0 h) was collected. Horses were administered CD intramuscularly at 1.8 mg/kg BW per label. Plasma samples were collected at 0.5, 1, 3, 6, 12, 24, 48, and 72 h post-administration. Plasma concentration of clodronate was determined by liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using a two-compartment model. Blood chemistry parameters [blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALKP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and creatine kinase (CK)] were determined via a commercial laboratory. Included blood chemistry parameters were analyzed for an effect of time using PROC Mixed of SAS. Clodronate was detected in plasma up to 72 h post-administration. Maximum plasma concentration (43,971 ± 25,920 ng/mL) was reached at 0.5 h post-administration. Analysis revealed bicompartmental kinetics with distribution and terminal half-lives of 1.9 ± 0.4 h and 24.4 ± 4.3 h, respectively. Area under the curve to last sample was 22,755 ± 11,426 ng*h/mL and extrapolated to infinity was 26,778 ± 12,465 ng*h/mL. Blood chemistry parameters varied over time within normal ranges. Markers of renal function, BUN and creatinine, decreased from h 0 to h 72 (P < 0.01). Liver function markers ALKP and AST were not affected by CD treatment (P > 0.27). However, GGT and CK changed over time (P < 0.01), with GGT greater at 48 h than other time points, and CK increasing from 0.5 to 24 h before decreasing by 72 h but remaining above baseline. Plasma clodronate concentrations were greater in juvenile horses than previously reported in mature horses (Krueger et al., 2020, Equine Vet J.; Knych et al., 2022, Equine Vet J.). Further, the observed bicompartmental kinetics differed from the linear kinetics previously reported in mature horses whereby juvenile horses from the current study had greater exposure to CD over time as indicated by a longer terminal half-life. Moreover, the single intramuscular dose of CD (1.8 mg/kg BW) did not cause markers of kidney or liver function to deviate from normal ranges in juvenile Quarter Horses.

The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece-A Randomized, Double-Blind, Placebo-Controlled Study.

The role of probiotic supplementation in type 2 diabetes (T2D) treatment is controversial. The present study aimed to assess the effects of a multi-strain probiotic supplement (LactoLevureR (containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii)) over 6 months, primarily on glycemic control as well as on lipid levels and alterations in the gut microbiome, among individuals with T2D residing in Greece. A total of 91 adults with T2D (mean age [±SD] 65.12 ± 10.92 years, 62.6% males) were randomized to receive the probiotic supplement or a matching placebo capsule, once daily, for 6 months. Blood chemistries and anthropometric parameters were conducted every 3 months, and stool samples were collected at baseline and at 6 months. Significant reductions in HbA1c, fasting blood glucose, and total cholesterol were observed in participants treated with the probiotic supplement (n = 46) compared to the controls (n = 45), even after adjustment for a greater decrease in adiposity (waist circumference). Although there were no statistically significant differences in the diversity of the gut microbiome (α and β diversity), the administration of probiotics did influence several genera, metabolites, and key enzymes associated with diabetes. Overall, the administration of the multi-strain probiotic LactoLevureR over a 6-month period in individuals with T2D was well-tolerated and had a positive impact on metabolic parameters, alongside improvements in indices of adiposity.

5-Aminolevulonic Acid, a New Tumor Contrast Agent: Anesthesia Considerations in Patients Undergoing Craniotomy

5-aminolevulinic acid (ALA) is used during resection of malignant gliomas due to its fluorescence properties and has been shown to render resection more effective than resection without ALA guidance. The aim of this narrative review is to categorize the adverse effects of ALA relevant to anesthesia providers. Intraoperative hypotension, porphyria-related side effects, alterations in blood chemistry and coagulation, photosensitivity, and increased levels of liver enzymes have all been reported. We also sought to examine the impact of dosage and timing of oral administration on efficacy of ALA and on these side effects. Twenty-seven studies met our inclusion criteria of patients undergoing craniotomy for glioma resection using ALA and occurrence of at least one adverse effect. The results of these studies showed that there was heterogeneity in levels of intraoperative hypotension, with some reporting an incidence as high as 32%, and that hypotension was associated with antihypertensive medication use. Clinical symptoms of porphyria, such as gastrointestinal disturbance, were less commonly reported. Photosensitivity of the skin after 5-ALA administration was well documented particularly in patients exposed to light; however, adverse effects on the eye were not adequately studied. Elevation in liver enzymes was a common finding postoperatively but was often clinically insignificant. The timing of oral administration presents practical issues for the preoperative management of patients undergoing resection with ALA. We provide guidance for perioperative management of patients who receive ALA for brain tumor resection. Controlled studies with adequate statistical power are required to further understand and prevent the adverse effects of ALA.

Fucoidan, as a marine bioactive substance, has shown great potential in regulating the bone-gut axis

Fucoidans exhibit numerous biological activities, including anti-inflammatory and hypolipidemic effects. Although its potential in regulating intestinal flora has been demonstrated, studies on its impact on bone metabolism and its relationship with the bone-gut axis remain limited. Therefore, this study was undertaken to explore the effects of fucoidan on the gut-bone axis in ovariectomized mice with osteoporosis. Twenty-one SPF ICR female mice were used in this study, distributed as follows: sham-operated (7), ovariectomized (7), and ovariectomized + fucoidan (200 mg/kg, 7). Subsequently, body indices, blood chemistry, bone specimens, short-chain fatty acids, fecal microbiota content, transmission electron microscopy, and RNA-seq transcriptome analysis were assessed, and statistical analysis was performed. The efficacy of fucoidan in treating osteoporosis was demonstrated in this study. Fucoidan treatment led to a significant increase in bone mineral density and procollagen N-terminal propeptide levels and a significant decrease in body weight and C-terminal peptide of human type I collagen and triglyceride levels (P < 0.05). Fucoidan promoted the health of ovariectomized mice, possibly by regulating the gut-bone axis. It significantly decreased the abundance of Ruminococcaceae UG-014, Parasutterella, and Muribaculum and increased the abundance of Akkermansia and Dubosiella (P < 0.05). Moreover, fucoidan protected the intestinal barrier and increased the acetic acid ratio. These changes in microbiota were significantly correlated with clinical features of osteoporosis (P < 0.05). Lipid metabolism emerged as a pivotal factor in the association between the intestinal microbiota and osteoporosis. Notably, intestinal transcriptome sequencing revealed significant changes in the expression of genes related to lipid metabolism (Adipoq, Angptl4, Adrb3, and C3ar1) and bone metabolism (Clec3b, Nrtn, Bpnt2, Ccn3, and Lama2) (P < 0.05). Overall, this study provides valuable insights into the unexplored microbiome-based mechanism by which fucoidan improves bone quality in ovariectomized mice, possibly by regulating the gut-bone axis.

Il supporto nutrizionale nell’anoressia nervosa

Paediatric departments are increasingly faced with adolescents with anorexia nervosa in severe nutritional and metabolic decompensation. Artificial nutritional support, often indispensable in the most critical phases of the course, requires careful evaluation of the clinical conditions at the time of hospitalization and equally punctual monitoring of blood chemistry variables during re-feeding. Prolonged reduced caloric intake and malnutrition, especially in its most extreme forms, can cause damage to various organs and systems and the refeeding syndrome must be kept in mind as a further comorbidity and aggravating factor of the patient's conditions. Through the description of a clinical case of particular complexity, some aspects related to the hospital treatment of anorexia nervosa are discussed.

Effect of multimorbidity on hypertension management

Multimorbidity, the coexistence of multiple health conditions, is associated with functional decline, disability, and mortality. We aimed to investigate the effects of multimorbidity on hypertension treatment and control rates by analyzing data from the Korean National Health and Nutrition Examination Survey database, which is a cross-sectional, nationally representative survey conducted by the Korean government. Multimorbidity, defined as having two or more chronic diseases, was evaluated by blood pressure measurements, blood chemistry examinations, and questionnaires. We classified the participants according to the number of multimorbidities from 0 to ≥ 6. Association analysis was performed to identify the patterns of multimorbidity related to hypertension control. From 2016 to 2020, 30,271 adults (≥ 20 years) were included in the analysis (age: 52.1 ± 16.8 years, male: 44.0%), and 14,278 (47.2%) had multimorbidity. The number of chronic conditions was significantly higher in older adults, women, and hypertensive patients. Multimorbidity was associated with hypertension treatment. The number of chronic conditions was significantly higher in controlled compared to uncontrolled patients (3.6 ± 1.7 vs 2.9 ± 1.6, p < 0.001). But the control rate of hypertension among treated patients was lower in patients with multimorbidity (75.6% in hypertension only group vs 71.8% in multimorbidity group, p = 0.009). Multimorbidity patterns showed distinct features in treated and controlled hypertensive patients. In conclusion, multimorbidity has a beneficial effect on the treatment of hypertension, but the control rate of systolic blood pressure was lower among the patients with multimorbidity. More attention should be paid to the hypertensive patients with multimorbidity to improve the control rate of hypertension.

Fibroblast Growth Factor 21 in Chronic Hepatitis C: A Potential Non-Invasive Biomarker of Liver Status upon Viral Eradication.

Fibroblast growth factor 21 (FGF-21), previously recognized as a marker of liver damage and a potential drug target in non-alcoholic fatty liver disease (NAFLD), has unclear implications in hepatitis C virus (HCV) infections. This study aimed to investigate the relationship between FGF-21 levels and liver health in patients with HCV undergoing direct-acting antiviral (DAA) treatment. Forty-five patients were assessed for liver stiffness, blood chemistry, and other relevant metrics before and after achieving sustained viral response (SVR), defined as the absence of detectable HCV-RNA after 24 weeks of treatment. Post-treatment, all patients showed a decrease in liver stiffness and improved liver enzyme levels (AST and ALT), alongside an increase in FGF-21 levels. Interestingly, the increase in FGF-21 correlated negatively with liver stiffness but showed no correlation with hepatic steatosis. The observed elevation in FGF-21 levels at SVR following DAA therapy for chronic HCV infection can be attributed to the restoration of hepatic function, including its synthetic capabilities. Specifically, the mitigation of liver fibrosis post-HCV eradication is expected to lead to improvements in liver function, such as enhanced albumin and FGF-21 production. This improvement in synthetic function likely drives the increase in FGF-21 levels, rather than changes in liver fat content. We suggest a potential role of FGF-21 as a marker of fibrosis and hepatic cytotoxicity and as a drug target beyond NAFLD, to be confirmed by additional studies.

Signature whistle use and changes in whistle emission rate in a rehabilitated rough-toothed dolphin

Acoustic signals play a crucial role in communication among animals, particularly in dolphins. Signature whistles, one of their most extensively studied vocalizations, enable dolphins to convey their identity to conspecifics through individually distinct whistle contours. However, it remains unclear whether rough-toothed dolphins (Steno bredanensis) also produce signature whistles with individually identifying contours and, if so, whether they are associated with stress and poor health, such as in bottlenose dolphins. To bridge this knowledge gap, we recorded sounds emitted by a live-stranded rough-toothed dolphin during its rehabilitation in May 2017 at Isla Mujeres, Quintana Roo, Mexico. We assessed if the dolphin produced a signature whistle and whether whistle rate, inter-whistle interval, mean low and high frequencies, and blood chemistry measures, changed significantly over time. While isolated from conspecifics during rehabilitation, the dolphin generated a single, repeated, and stereotyped whistle contour that met the previously established SIGnature IDentification criteria for signature whistle emissions for bottlenose dolphins. Whistle characteristics varied over the 11 recording days: whistle rate and inter-whistle interval significantly decreased over time; the number of whistles with preceding echolocation click trains decreased over time; and mean low and high frequencies changed over recording days. We conclude that this rough-toothed dolphin possessed what resembles a signature whistle contour, and the emission of this contour underwent significant changes throughout the rehabilitation process. While our study presents evidence of a single rough-toothed dolphin producing a signature whistle, further research is necessary to determine whether this vocal behavior is prevalent across the species.