THERAPEUTIC AND SAFETY EVALUATION OF CURCUMIN\u27S ANTIMICROBIAL AND ANTI-INFLAMMATORY PROPERTIES ON CANINE AND EQUINE

In total, four experiments were conducted to determine the therapeutic and safety effects of the nutraceutical, turmeric and its active ingredient curcumin on canine and equine. Two studies were conducted on client-owned, moderately arthritic canines, studying the therapeutic and safety effect of curcumin’s anti-inflammatory properties. In Exp. 1, two different dosages, 500 mg, SID of 95% curcumin and 250 mg, BID of 95% liposomal-curcumin, were evaluated in ten moderately arthritic dogs over five months. The dogs in the 95% curcumin group had an overall greater significance in pain reduction by Day 60. Exp. 2, was a follow-up experiment to Exp. 1. In Exp. 2, two different dosages, 500 mg, SID or 100 mg, SID of 95% curcumin, were evaluated in ten moderately arthritic dogs over five months. Findings showed that dogs in the 500 mg, SID group had an overall greater significance in pain reduction by Day 60. Experiment 3 and 4 were a two-part project looking at the anti-microbial and anti-inflammatory properties of turmeric, curcumin, and liposomal-curcumin in cecally-cannulated equine. Exp. 3, was a two-part in vitro study, the first part looked at the anti-microbial effects of turmeric, curcumin, and liposomal-curcumin in reducing opportunistic bacteria found in the equine hindgut, including Streptococcus bovis/equinus complex (SBEC) (P = 0.0056), E. coli K-12 (P = 0.5114), Escherichia coli general (P = 0.1083), Clostridium difficile (P \u3c 0.001), and Clostridium perfringens (P = 0.2439). Treatment D, 95% liposomal-curcumin, numerically reduced the concentration of all five opportunistic strains, and was therefore selected for use in the follow-up in vitro experiment. The second in vitro studied the effects of four different dosages, 15 g, 20 g, 25g, and 30 g of 500 mg/g of 95% liposomal-curcumin at reducing the concentration of SBEC (P \u3c 0.0001), E. coli K-12 (P = 0.0124), E.coli general (P = 0.032), C. difficile (P = 0.5608), and C. perfringens (P = 0.4214). In Exp. 4, 500 mg/g of 95% liposomal-curcumin at 15 g, 25 g, and 35 g, were tested in vivo for anti-inflammatory and anti-microbial therapeutic effects. In total, four experiments were conducted to determine the therapeutic and safety effects of the nutraceutical, turmeric, and its active ingredient curcumin on canines and equines. Two studies were conducted on client-owned, moderately arthritic canines, studying the therapeutic and safety effect of curcumin’s anti-inflammatory properties. In Exp. 1, two different dosages, 500 mg, SID of 95% curcumin and 250 mg, BID of 95% liposomal-curcumin, were evaluated in ten moderately arthritic dogs over five months. The dogs in the 95% curcumin group, overall, had a greater reduction in pain by Day 60. Exp. 2, was a follow-up experiment to Exp. 1. In Exp. 2, two different dosages, 500 mg, SID or 100 mg, SID of 95% curcumin, were evaluated in ten moderately arthritic dogs over five months. We observed that dogs in the 500 mg, SID group had an overall greater significance in pain reduction by Day 60. Experiment 3 and 4 were conducted as a two-part project looking at the antimicrobial and anti-inflammatory properties of turmeric, curcumin, and liposomal-curcumin. The purpose of these studies were to investigate both form and dose of turmeric and its active ingredient, curcumin, on reducing opportunistic bacteria found in the equine hindgut. The bacterial strains of interest included Streptococcus bovis/equinus complex (SBEC), Escherichia coli K-12, Escherichia coli general, Clostridium difficile, and Clostridium perfringens. Exp. 3, was a two-part in vitro study; the first part looked at the antimicrobial effects of turmeric, curcumin, and liposomal-curcumin (LIPC) on reducing opportunistic bacteria found in the equine hindgut, including SBEC (P = 0.006), E. coli K-12 (P = 0.50), E. coli general (P = 0.11), C. difficile (P \u3c 0.0001), and C. perfringens (P = 0.24). The follow-up in vitro 24 h batch culture examined four different dosages (15 g, 20 g, 25 g, and 30 g) of 500 mg/g of LIPC, at reducing the concentration of opportunistic bacteria. These results were utilized to determine the dosing rate in vivo. Exp. 3, in vitro, evaluated the efficacy of antimicrobial and anti-inflammatory properties of LIPC dosed at 15, 20, 25, and 35 g. These results were utilized to determine the dosing rate in vivo. Exp. 4, in vivo, evaluated the efficacy of antimicrobial and anti-inflammatory properties of LIPC dosed at 15, 25, and 35 g compared to a control. In vivo, LIPC’s antimicrobial properties, at 15 g, significantly decreased (P = 0.02) SBEC compared to other treatments. In addition, C. perfringens tended (P = 0.12) to decrease as LIPC dose increased. Non-significant results in digestion, blood parameters, and range of motion suggest there were no adverse side effects from oral dosing increasing doses of curcumin. Valerate decreased (P = 0.005) linearly as LIPC dose increased. As LIPC dose increased, butyrate and iso-valerate decreased (P ≤ 0.03) linearly. However, acetate tended (P = 0.10) to increase linearly as the dose of LIPC increased. Treatment did not affect (P ≥ 0.19) any of the other individual VFAs measured, but increasing doses of LIPC tended (P = 0.10) to increase total VFA concentrations. Additionally, LIPC tended (P = 0.11) to increase total VFA concentrations when compared to control. In the future, further work should be conducted examining liposomal-curcumin’s antimicrobial properties in canine and anti-inflammatory properties in equine over a longer period of tim

Exercise-based multimodal programming : A treatment gap for older adults with advanced cancer [Commentary]

[Extract] Approximately 60% of new cancer diagnoses occur in patients aged 65 years and older.1 Normal aging is associated with a decline in health and physical function.2 A cancer diagnosis and subsequent treatment can accelerate this age-related physical decline, increasing the risk of adverse health events and mortality.1 Aerobic and resistance exercise is an effective therapy to improve physical fitness and quality of life and to reduce cancer-related fatigue in individuals diagnosed with cancer, including advanced cancer.3 The American College of Sports Medicine guidelines recommend maintenance of physical activity during active cancer treatment,3 but guidelines specific to advanced cancer or elderly populations are lacking. Older patients with cancer are vastly underrepresented in clinical trials, including exercise-based trials,4 due in part to the challenges introduced by the observed heterogeneity among older adults with respect to comorbid conditions, functional status, motivation, and safety-related concerns of the treating health care professionals.4 Older adults are more likely to fear physical activity due to potential injury and to lack of guidance regarding how to start exercising.5,

A Pilot Study on the Effects of Curcumin on Parasites, Inflammation, and Opportunistic Bacteria in Riding Horses

Twelve riding horses were utilized to examine the effects of curcumin on intestinal parasites, inflammation, and the fecal shedding of Streptococcus bovis/equinus complex (SBEC), Clostridium difficile and Clostridium perfringens. Known for having anti-inflammatory, antimicrobial, and antiparasitic properties it was hypothesized that curcumin would decrease parasite shedding, inflammation, and opportunistic bacteria found in the GIT of riding horses. Horses were randomly assigned to one of the following treatments (n = 6/treatment): 1) no curcumin, control (CON); or 2) 15 g of 95% pure curcumin, (CUR). Curcumin was dosed per day for 30 d. Fecal samples were evaluated for shedding of ova and concentrations of selected bacteria. Blood samples taken pre and post riding intervals and evaluated for erythrocyte sedimentation rate (ESR) for inflammation. All data were analyzed for repeated measures. Treatment had no effect (P ≥ 0.58) on total fecal egg count, strongyles, or ascarids. Treatment had no effect on ESR (P ≤ 0.42); however, ESR decreased (P = 0.0006) on d 14 in CUR horses. Treatment had no effect (P ≥ 0.34) on concentrations of SBEC, C. difficile, or C. perfringens. Curcumin was not an effective compound against intestinal parasites or fecal microbial strains examined when administered for 30 days; but could potentially decrease inflammation. Curcumin has been observed to have many beneficial effects in other species, however, more research is needed to evaluate those benefits in horses

Effect of Grazing Muzzles on the Rate of Pelleted Feed Intake in Horses

Esophageal obstruction or “choke” is a relatively common occurrence in the equine industry. It often results from improper mastication, consuming feed too quickly, dehydration or a decrease in saliva production. Esophageal obstruction is a medical emergency during which a horse cannot dislodge a bolus of feed from the esophagus and must wait for human intervention or for the block to be softened and moved by peristalsis. This condition may result in the formation of ulcers, esophageal rupture, aspiration pneumonia, and possibly death. Grazing muzzles have been shown to slow the rate of forage intake. We hypothesized that grazing muzzles could also be used to decrease the rate of pelleted feed intake and so possibly reduce the risk of equine esophageal obstruction in horses fed large meals of pelleted feed. The objective of this research was to compare the rate of pelleted feed intake for horses wearing grazing muzzles to those wearing no muzzle. Utilizing a crossover design, horses were randomly assigned to three groups with each horse receiving each treatment. Treatments were as follows: No Muzzle (NM), Easy Breath Grazing Muzzle (EBGM), or Tough 1 Nylon Grazing Muzzle (TNGM). Eight adult stock-type horses age 5 ±1 years, were offered 2.27 kg of pelleted concentrate to consume in a 10-minute period once daily. The study was comprised of three periods (5 days each) with a two-day resting period between each. Horses were weighed daily and no significant change in bodyweight was observed. Data for daily intake were analyzed using the PROC MIXED procedure of SAS with significance established at P \u3c 0.05. Both the EBGM and the TNGM reduced rate of intake (P \u3c 0.05) during a 10-minute feeding interval as compared with NM. The findings of this study revealed that grazing muzzles may be a viable option to reduce the rate of intake of pelleted feed, which may benefit horses susceptible to choke as a 31 result of rapid feed ingestion

Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review

Background: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. Methods: We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. Results: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. Conclusions: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses

Understanding the yeast host cell response to recombinant membrane protein production

Membrane proteins are drug targets for a wide range of diseases. Having access to appropriate samples for further research underpins the pharmaceutical industry's strategy for developing new drugs. This is typically achieved by synthesizing a protein of interest in host cells that can be cultured on a large scale, allowing the isolation of the pure protein in quantities much higher than those found in the protein's native source. Yeast is a popular host as it is a eukaryote with similar synthetic machinery to that of the native human source cells of many proteins of interest, while also being quick, easy and cheap to grow and process. Even in these cells, the production of human membrane proteins can be plagued by low functional yields; we wish to understand why. We have identified molecular mechanisms and culture parameters underpinning high yields and have consolidated our findings to engineer improved yeast host strains. By relieving the bottlenecks to recombinant membrane protein production in yeast, we aim to contribute to the drug discovery pipeline, while providing insight into translational processes

Lymphatic function is required prenatally for lung inflation at birth

Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants

The GALAH Survey: Chemical tagging and chrono-chemodynamics of accreted halo stars with GALAH+ DR3 and GaiaGaia eDR3

© 2021 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stab3504Since the advent of $Gaia$ astrometry, it is possible to identify massive accreted systems within the Galaxy through their unique dynamical signatures. One such system, $Gaia$-Sausage-Enceladus (GSE), appears to be an early "building block" given its virial mass $> 10^{10}\,\mathrm{M_\odot}$ at infall ($z\sim1-3$). In order to separate the progenitor population from the background stars, we investigate its chemical properties with up to 30 element abundances from the GALAH+ Survey Data Release 3 (DR3). To inform our choice of elements for purely chemically selecting accreted stars, we analyse 4164 stars with low-$\alpha$ abundances and halo kinematics. These are most different to the Milky Way stars for abundances of Mg, Si, Na, Al, Mn, Fe, Ni, and Cu. Based on the significance of abundance differences and detection rates, we apply Gaussian mixture models to various element abundance combinations. We find the most populated and least contaminated component, which we confirm to represent GSE, contains 1049 stars selected via [Na/Fe] vs. [Mg/Mn] in GALAH+ DR3. We provide tables of our selections and report the chrono-chemodynamical properties (age, chemistry, and dynamics). Through a previously reported clean dynamical selection of GSE stars, including $30 < \sqrt{J_R~/~\mathrm{kpc\,km\,s^{-1}}} < 55$, we can characterise an unprecedented 24 abundances of this structure with GALAH+ DR3. Our chemical selection allows us to prevent circular reasoning and characterise the dynamical properties of the GSE, for example mean $\sqrt{J_R~/~\mathrm{kpc\,km\,s^{-1}}} = 26_{-14}^{+9}$. We find only $(29\pm1)\%$ of the GSE stars within the clean dynamical selection region. Our methodology will improve future studies of accreted structures and their importance for the formation of the Milky Way.Peer reviewedFinal Accepted Versio