Systematic review and QSPR analysis of chemical penetration through the nail to inform onychomycosis candidate selection.

Recalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided by the SPIDER method, we extracted chemical nail permeation data for 38 compounds from 16 articles, and analyzed the data using quantitative structure-property relationships (QSPRs). Our analysis demonstrated that low-molecular weight was essential for effective nail penetration, with <120 g/mol being preferred. Interestingly, chemical polarity had little effect on nail penetration; therefore, small polar molecules, which effectively penetrate the nail, but not the skin, should be set as the most desirable target chemical property in new post-screen onychomycosis candidate selections.

Non-Antibiotic Compounds Synergistically Kill Chronic Wound-Associated Bacteria and Disrupt Their Biofilms.

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, Staphylococcus aureus and Pseudomonas aeruginosa, were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both S. aureus and P. aeruginosa and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues.

Growth, carcass and meat quality characteristics of Charolais-sired steers and heifers born to Angus-cross-dairy and Angus breeding cows.

Charolais-sired heifers and steers from Angus, Angus × Holstein-Friesian, Angus × Holstein-Friesian-Jersey and Angus × Jersey cows were measured for growth, carcass, and meat quality characteristics. Despite differences in weaning weight and growth rate, the progeny of different breed-crosses did not differ in final live weight or carcass weight (P > 0.05). Carcass and meat quality characteristics did not differ among breed-crosses (P > 0.05), except for fat that was more yellow in progeny from Angus and Angus-cross-Jersey dams. Steers were slaughtered older and had heavier carcasses with greater fat depth and intramuscular fat than heifers. Meat quality differed between the sex classes, with steers having greater pH and shear force, redder meat, and yellower fat than heifers. Angus-cross-dairy cows when crossed with a beef breed sire such as the Charolais will provide progeny for meat production which are competitive to beef breeds for beef finishing and meat production and therefore, a useful mechanism to utilize surplus animals from the dairy industry.

Antibiotics-Free Compounds for Chronic Wound Healing.

The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections affecting patients' quality of life. Unfortunately, antibiotics are not always helpful due to their poor penetration of bacterial biofilms and the emergence of antimicrobial resistance. Hence, there is an urgent need to explore antibiotics-free compounds/formulations with proven or potential antimicrobial, anti-inflammatory, antioxidant, and wound healing efficacy. The mechanism of antibiotics-free compounds is thought to include the disruption of the bacteria cell structure, preventing cell division, membrane porins, motility, and the formation of a biofilm. Furthermore, some of these compounds foster tissue regeneration by modulating growth factor expression. In this review article, the focus is placed on a number of non-antibiotic compounds possessing some of the aforementioned pharmacological and physiological activities. Specific interest is given to Aloevera, curcumin, cinnamaldehyde, polyhexanide, retinoids, ascorbate, tocochromanols, and chitosan. These compounds (when alone or in formulation with other biologically active molecules) could be a dependable alternative in the management or prevention of chronic wounds.

Estimated Breeding Values of Beef Sires Can Predict Performance of Beef-Cross-Dairy Progeny.

On average, half of the animal's estimated breeding value (EBV) is passed on to their progeny. However, it is not known how the performance of beef-cross-dairy cattle relates to the EBV of their beef sire. Such information is required to determine the genetic potential of beef sires selected based on existing EBV to be used on dairy cows in New Zealand. This study evaluated the relationship between the EBV of 30 Angus and 34 Hereford sires and the performance of their progeny for birth, growth, and carcass traits, via progeny testing of 975 beef-cross-dairy offspring born to dairy cows and grown on hill country pasture. Overall, BREEDPLAN EBV did predict progeny performance of the beef-cross-dairy cattle from this study. Gestation length and birthweight increased with increasing sire EBV (mean 0.37-0.62days and 0.52-0.64kg, respectively, p<0.05). Age at weaning decreased with increasing sire EBV for liveweight at 200days (0.17-0.21days per extra kilo of sire EBV, p<0.05) but sire EBV for liveweight at 200days had no effect on the liveweight of the progeny at 200days for either breed (p>0.05). Liveweight increased with sire EBV for liveweight at 400, 600, and 800days, by a similar amount for both breeds (between 0.23 and 0.42kg increase in progeny liveweight per extra kilo of sire EBV, p<0.05). The relationships were more inconsistent for carcass traits. For Hereford, carcass weight and eye muscle area increased with increasing sire EBV (0.27kg and 0.70cm2, respectively, p<0.05). For Angus, marble score increased by 0.10 with 1% extra in sire EBV for intramuscular fat (p<0.05). Rib fat depth tended to increase with sire EBV for both breeds (p<0.1). EBV derived from beef-breed data work in dairy-beef systems but maybe slightly less than the expected 0.5units of performance per unit of EBV. New Zealand farmers should consider BREEDPLAN EBV when selecting sires to mate dairy cows or when buying beef-cross-dairy calves for beef production, to ensure the resulting calves are born safely and on time and then grow well to produce carcasses of suitable meat and fat composition.

In Silico Simulation of Simultaneous Percutaneous Absorption and Xenobiotic Metabolism: Model Development and a Case Study on Aromatic Amines.

PURPOSE: To advance physiologically-based pharmacokinetic modelling of xenobiotic metabolism by integrating metabolic kinetics with percutaneous absorption. METHOD: Kinetic rate equations were proposed to describe the metabolism of a network of reaction pathways following topical exposure and incorporated into the diffusion-partition equations of both xenobiotics and metabolites. The published ex vivo case study of aromatic amines was simulated. Diffusion and partition properties of xenobiotics and subsequent metabolites were determined using physiologically-based quantitative structure property relationships. Kinetic parameters of metabolic reactions were best fitted from published experimental data. RESULTS: For aromatic amines, the integrated transdermal permeation and metabolism model produced data closely matched by experimental results following limited parameter fitting of metabolism rate constants and vehicle:water partition coefficients. The simulation was able to produce dynamic concentration data for all the dermal layers, as well as the vehicle and receptor fluid. CONCLUSION: This mechanistic model advances the dermal in silico functionality. It provides improved quantitative spatial and temporal insight into exposure of xenobiotics, enabling the isolation of governing features of skin. It contributes to accurate modelling of concentrations of xenobiotics reaching systemic circulation and additional metabolite concentrations. This is vital for development of both pharmaceuticals and cosmetics.

Carcass characteristics and meat quality of Hereford sired steers born to beef-cross-dairy and Angus breeding cows.

Steers from Angus, Angus×Holstein Friesian, Angus×Holstein Friesian-Jersey and Angus×Jersey cows and a Hereford sire were measured for their carcass and meat quality characteristics. Steers from the Angus×Holstein Friesian cows had a greater final body weight and carcass weight (P<0.05). Steers from Angus×Jersey cows had the lowest carcass weight and dressing-out percentage (P<0.05). There was a greater fat depth over the rump at 12 and 18months of age for the steers from Angus cows (P<0.05) but, not at 24months of age. The steers had similar meat quality characteristics across the breed groups. Steers from Angus×Holstein Friesian and Angus×Jersey cows had a higher ratio of n6 to n3 fatty acids. Using beef-cross-dairy cows to produce steers for meat production does not impact on meat quality. Using Jersey in the breed cross reduced the carcass tissues in the live weight and the potential meat yield.